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A severe, early-onset form of axonal CMT peripheral sensorimotor polyneuropathy. ## Epidemiology ARCMT2K was originally described in three Spanish families and has since been described in five additional Spanish kindreds, as well as in families from Morocco, France and Poland. ## Clinical description Onset occurs in the neonatal period or early infancy with a clinical picture similar to that seen in CMT4A (another autosomal recessive form of CMT4 but with a demyelinating phenotype; see this term) including hypotonia, scoliosis, a hoarse voice, vocal cord paralysis and respiratory insufficiency. However, nerve conduction velocities and pathological findings from sural nerve biopsies in ARCMT2K patients are indicative of a predominantly axonal neuropathy with some demyelinating features. ## Etiology ARCMT2K is caused by mutations in the GDAP1 gene (8q13.3), encoding a protein required for mitochondrial fission. Mutations in the same gene are associated with CMT4A and with a milder, later-onset autosomal dominant axonal form of CMT, CMT2K (see this term). ## Prognosis The prognosis for ARCMT2K may be severe, with two of the reported patients dying during in the fifth decade of life. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Autosomal recessive Charcot-Marie-Tooth disease with hoarseness	c1842983	27,000	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=101097	2021-01-23T17:20:36	{"gard": ["12448"], "mesh": ["C535418"], "omim": ["607706", "607831"], "umls": ["C1842983"], "icd-10": ["G60.0"], "synonyms": ["ARCMT2K", "Autosomal recessive axonal CMT4C4", "Autosomal recessive axonal Charcot-Marie-Tooth disease type 2K"]}
Vaginal intraepithelial neoplasia SpecialtyOncology Vaginal intraepithelial neoplasia (VAIN) is a condition that describes premalignant histological findings in the vagina characterized by dysplastic changes.[1] The disorder is rare and generally has no symptoms.[2] VAIN can be detected by the presence of abnormal cells in a Papanicolaou test (Pap smear).[2] Like cervical intraepithelial neoplasia, VAIN comes in three stages, VAIN 1, 2, and 3.[3] In VAIN 1, a third of the thickness of the cells in the vaginal skin are abnormal, while in VAIN 3, the full thickness is affected.[3] VAIN 3 is also known as carcinoma in-situ, or stage 0 vaginal cancer.[3] Infection with certain types of the human papillomavirus ("high-risk types") may be associated with up to 80% of cases of VAIN.[4] Vaccinating with HPV vaccine before initial sexual contact has been shown to reduce incidence of VAIN.[5] ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 1192. ISBN 978-1-4160-2999-1. 2. ^ a b Diakomanolis, E; Stefanidis, K; Rodolakis, A; Haidopoulos, D; Sindos, M; Chatzipappas, I; Michalas, S (2002). "Vaginal intraepithelial neoplasia: report of 102 cases". European Journal of Gynaecological Oncology. 23 (5): 457–9. PMID 12440826. 3. ^ a b c Cancer Research UK (2002). The stages of cancer of the vagina Archived 2007-10-07 at the Wayback Machine. CancerHelp UK. Retrieved January 3, 2008. 4. ^ Cancer Research UK (2002). Risks and causes of vaginal cancer Archived 2007-10-07 at the Wayback Machine. CancerHelp UK. Retrieved January 3, 2008. 5. ^ "FDA Approves Expanded Uses for Gardasil to Include Preventing Certain Vulvar and Vaginal Cancers". 2008-09-12. Retrieved 2010-02-13. ## External links[edit] Classification D * ICD-9-CM: 233.31 * 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 Human papillomavirus Related diseases Cancers * Cervical cancer * cancers * Anal * Vaginal * Vulvar * Penile * Head and neck cancer (HPV-positive oropharyngeal cancer) Warts * * genital * plantar * flat * Laryngeal papillomatosis * Epidermodysplasia verruciformis * Focal epithelial hyperplasia * Papilloma Others Acrochordon (skin tags) Vaccine * HPV vaccines * Cervarix * Gardasil Screening * Pap test: * stain * Bethesda system * Cytopathology * Cytotechnology * Experimental techniques: * Speculoscopy * Cervicography Colposcopy Biopsy histology * Cervical intraepithelial neoplasia (CIN) * Koilocyte * Vaginal intraepithelial neoplasia (VAIN) * Vulvar intraepithelial neoplasia (VIN) Treatment * Cervical conization * Loop electrical excision procedure (LEEP) History * Georgios Papanikolaou * Harald zur Hausen This oncology article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Vaginal intraepithelial neoplasia	c0346208	27,001	wikipedia	https://en.wikipedia.org/wiki/Vaginal_intraepithelial_neoplasia	2021-01-18T18:56:45	{"icd-9": ["233.31"], "wikidata": ["Q1781177"]}
A hereditary disorder of bilirubin metabolism characterized by unconjugated hyperbilirubinemia due to reduced and inducible activity of hepatic bilirubin glucuronosyltransferase (GT). Crigler-Najjar syndrome type 2 (CNS2) is a milder form of Crigler-Najjar syndrome (CNS) than Crigler-Najjar syndrome type 1 (CNS1). ## Epidemiology The prevalence of CNS2 is unknown. CNS has an estimated annual incidence at birth of 1/1,000,000. ## Clinical description First clinical manifestations usually appear soon after birth. CNS2 patients are less severely jaundiced than CNS1 patients, have pigmented bile that contains bilirubin glucuronides, and generally do not present neurologic or intellectual impairment. Bilirubin encephalopathy may develop in later life when patients experience a superimposed infection or stress. ## Etiology Numerous mutations in the UGT1A1 gene on 2q37 are linked to CNS2 and result in reduced bilirubin GT activity, with marked impairment of bilirubin conjugation. ## Diagnostic methods Diagnosis is based on biochemical findings with total serum bilirubin ranging from 6 to 20 mg/dL and presence of bilirubin glucuronides in bile. Diagnosis is confirmed by genomic DNA analysis (ruling out the need for liver biopsy). It may also help in differentiating between the two types of CNS. Liver biopsy, when it was performed, revealed residual enzymatic activity. ## Differential diagnosis Differential diagnosis includes disorders of excessive bilirubin production (hemolysis) and impaired hepatic handling of bilirubin (hepatitis and Gilbert syndrome; see this term). CNS2 can be differentiated from CNS1 by measurement of transferase activity and the response to phenobarbital treatment. ## Antenatal diagnosis Antenatal diagnosis is not usually indicated for CNS2. ## Genetic counseling The mode of inheritance is autosomal recessive. ## Management and treatment Treatment relies on daily phenobarbital administration that can induce the expression of bilirubin GT resulting in a decrease in the serum bilirubin level by approximately 60-70%. Patients and their families must be educated to be very careful during infectious episodes and/or fasting periods that are likely toincrease bilirubin production and thus increase hyperbilirubinemia. Should this occur, patients must be examined by their physician and serum bilirubin concentration must be measured. ## Prognosis Prognosis is good: this form does not cause cognitive or motor impairment during childhood. Adult patients remain jaundiced and must continue phenobarbital treatment throughout their 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Crigler-Najjar syndrome type 2	c2931132	27,002	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79235	2021-01-23T18:50:45	{"gard": ["8683"], "mesh": ["C536213"], "omim": ["606785"], "umls": ["C0268311", "C2931132"], "icd-10": ["E80.5"], "synonyms": ["Arias syndrome", "Bilirubin uridinediphosphate glucuronosyltransferase deficiency type 2", "Bilirubin-UGT deficiency type 2", "Hereditary unconjugated hyperbilirubinemia type 2", "UGT deficiency type 2"]}
A demyelinating disorder of the central nervous system. ## Epidemiology The incidence rate has been estimated at 1 in 125,000-250,000 per year. ## Clinical description Children younger than 10 years are predominantly affected. A seasonal winter and spring peaks have been registered. The disease usually develops after acute viral or bacterial infection or vaccination, with a sudden onset of irritability and lethargy after a prodromal period of 1-4 weeks. Major symptoms include fever, headache, drowsiness, changes in mental status, seizures and coma. Weakness, vomiting, weight loss, stiff neck, ataxia, bilateral optic neuritis and delirium are common. Peripheral nervous system involvement (paralysis of a single limb or hemiplegia) occurs in 5-45% of cases, according to literature data. Although initially the symptoms of ADEM may be mild, they worsen rapidly within several hours to four days. Pathologically, ADEM is characterized by bilateral large and confluent lesions in cerebral and cerebellar white matter; basal ganglia and gray matter may also be involved. ADEM lesions in the spinal cord are continuous and extending to multiple levels. Some authors consider the disease as a variant or borderline form of multiple sclerosis (MS) (see this term). ## Etiology ADEM is considered as an immune-mediated disorder of the central nervous system. It can arise spontaneously but in most cases the disease is triggered by infectious disease or vaccinations. Links between the Pasteur rabies vaccine and ADEM have been documented. Immunizations less frequently associated with ADEM include pertussis, measles, Japanese B virus, tetanus, influenza. ## Diagnostic methods Diagnosis is based on the clinical history and magnetic resonance imaging, which is the diagnostic modality of choice. ## Differential diagnosis MS is the main differential diagnosis. The differentiation between ADEM and a first episode of MS can be very difficult but has important prognostic and treatment implications. Differential diagnosis also includes infectious encephalitis, Guillain-Barré syndrome, glioblastoma multiforme, Schilder's disease (see these terms), psychotic disorders with acute onset, toxic/metabolic encephalopathy, vasculitis, nonvasculitic autoimmune encephalopathy, meningitis, metastatic tumor. ## Management and treatment Currently, immunosuppression with corticosteroids for the acute events is the mainstay of treatment. In patients refractory to steroid therapy, plasmapheresis or intravenous immunoglobulin therapy can be used. Symptomatic and supportive treatments are recommended. ## Prognosis ADEM is typically a monophasic (single episode) disease with generally favorable outcome. Average time to recover is one to six months. Relapses may occur in 5-25% of cases, generally 6-18 months after the onset. Fulminant presentation with cerebral edema requiring critical intensive care is rare. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Acute disseminated encephalomyelitis	c0014059	27,003	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=83597	2021-01-23T18:42:42	{"gard": ["8639"], "mesh": ["D004673"], "umls": ["C0014059"], "icd-10": ["G04.0"], "synonyms": ["ADEM", "Acute disseminated encephalitis"]}
## Description Obstructive sleep apnea is a common, chronic, complex disease associated with serious cardiovascular and neuropsychologic sequelae and with substantial social and economic costs (Palmer et al., 2003). Clinical Features Strohl et al. (1978) described 2 males and their father with severe hypersomnolence and obstructive sleep apnea. A third son, although asymptomatic, was shown to have upper-airway obstruction during sleep. Electromyographic recordings of genioglossal muscle activity showed loss of tonic activity in early stages of sleep when sleep apnea occurred. (The bilateral genioglossus muscles play a crucial role in the normal mechanism for maintaining a patent oropharyngeal lumen, especially during sleep in the supine position, for they are the muscles that force the tongue forward during inspiration.) The asymptomatic son showed loss of tonic activity during rapid-eye-movement sleep, the period when upper-airway obstruction occurred. A fourth son died in his sleep at age 30 years and a daughter of the asymptomatic brother (member of the third generation) died at age 4 months from presumed sudden-infant-death syndrome. The tongue may be responsible for airway obstruction in this seemingly hereditary syndrome. Daytime somnolence was striking in these persons and narcolepsy (161400) had been diagnosed in some. When the subjects slept, observers described restless movements, loud snorts and snoring, and long periods of apnea. Manon-Espaillat et al. (1988) described a family in which sleep apnea was associated with partial complex seizures and anosmia and segregated in an autosomal dominant pattern. Both the proband and his affected father had seizure disorder; in addition, the proband and his brother were colorblind. The authors designated this 'familial sleep apnea plus' syndrome. Guilleminault et al. (1995) conducted a mail survey of first-degree relatives of 157 subjects with obstructive sleep apnea syndrome and friends who were approximately the same age who were not relatives of the index case. A more extensive investigation was performed on first-degree relatives of the index group living in the San Francisco Bay area or vicinity. The latter investigation indicated that, when first first-degree relatives were compared with friends, the complaint of daytime tiredness, sleepiness, or both with the presence of a high and narrow (ogival) hard palate sharply differentiated between friends and relatives. Disproportionate craniofacial anatomy, as indicated by cephalometric x-ray films, was common in familial groups with OSAS. They concluded that craniofacial familial features can be a strong indicator of risk for the development of OSAS. Mojon et al. (2002) found a high prevalence of sleep apnea syndrome in patients with nonarteritic anterior ischemic optic neuropathy (NAION; 258660), which supported previous case reports suggesting that such an association existed. This association might explain why approximately 75% of all patients with NAION discovered visual loss upon first awakening or when they first used vision critically after sleeping. The authors stated that sleep apnea syndrome may play an important role in the pathogenesis of NAION. Svatikova et al. (2003) found that plasma levels of serum amyloid A1 (SAA1; 104750) were more than 2-fold greater in patients with moderate to severe obstructive sleep apnea compared with subjects with mild obstructive sleep apnea or healthy controls regardless of gender. The authors concluded that elevated SAA1 may contribute to any increased risk for cardiovascular and neuronal dysfunction in patients with obstructive sleep apnea. Inheritance Rostand (1978) observed an affected man with an affected son and brother, suggesting autosomal dominant inheritance. Douglas et al. (1993) did a prospective study of first-degree relatives of 20 consecutive nonobese patients with the sleep apnea/hypopnea syndrome. They concluded that there is an increased frequency of abnormal breathing during sleep in relatives. Teculescu et al. (1994) found evidence for a 'familial factor' in habitual snoring. Redline and Tishler (2000) reviewed the data suggesting that there are 'strong genetic underpinnings' for obstructive sleep apnea hypopnea syndrome. They cited an estimate of 40% of the variance in the apnea hypopnea index being explained by familial factors. They suggested that genetic factors associated with craniofacial structure, body fat distribution, and neural control of the upper airway muscles interact to produce the OSAS phenotype. Mapping Along with male gender, obesity is the most common characteristic of OSA in adults. To identify susceptibility loci for OSA, Palmer et al. (2003) performed a 9-cM genome scan in 66 white pedigrees ascertained on the basis of either an affected individual with laboratory-confirmed OSA or a proband who was a neighborhood control individual. Multipoint variance component linkage analysis was performed for the OSA-associated quantitative phenotypes apnea-hypopnea index (AHI) and BMI. Candidate regions on chromosomes 1p (lod score 1.39), 2p (lod score 1.64), 12p (lod score 1.43), and 19p (lod score 1.40) gave the most evidence for linkage to AHI. BMI was also linked to multiple regions, most significantly to markers on 2p (lod score 3.08), 7p (lod score 2.53), and 12p (lod score 3.41). Extended modeling indicated that the evidence for linkage to AHI was effectively removed after adjustment for BMI, with the exception of the candidate regions on 2p (adjusted lod score 1.33) and 19p (adjusted lod score 1.45). After adjustment for AHI, the primary linkages to BMI remained suggestive but were roughly halved. The results suggested that there are both shared and unshared genetic factors underlying susceptibility to OSA and obesity and that the interrelationship of OSA and obesity in white individuals may be partially explained by a common causal pathway involving one or more genes regulating both AHI and BMI levels. Molecular Genetics Kadotani et al. (2001) studied apolipoprotein E4 (107741) in relation to sleep apnea because apoE4 is a risk factor for Alzheimer disease (AD; 104300) and cardiovascular disease, and sleep-disordered breathing occurs in AD patients and increases the risk for cardiovascular disease. Using nocturnal polysomnography to evaluate the apnea-hypopnea index in 791 middled-aged adults, they found that the probability of moderate to severe sleep-disordered breathing was significantly higher in participants with apoE4, independent of age, sex, body mass index (BMI), and ethnicity. These effects increased with the number of apoE4 alleles carried. In a study of 1,775 individuals, Gottlieb et al. (2004) found an age-dependent association between the APOE4 allele and obstructive sleep apnea. APOE4 carriers younger than 65 years had an odds ratio of 3.08 for sleep apnea, whereas APOE4 carriers 65 years of age or older had an odds ratio of 1.25. The association was stronger in those with hypertension or cardiovascular disease. Among 18 older adult APOE4 carriers with obstructive sleep apnea, O'Hara et al. (2005) found an association between greater numbers of respiratory events and lower memory performance. No association was found in 18 older adult noncarriers with sleep apnea. The authors suggested that sleep apnea may partly account for the association of the E4 allele and cognitive decline in community-dwelling older adults and postulated that hypoxia may have a role in neuronal vulnerability to oxidative stress. Gozal et al. (2007) found that the APOE E4 allele was more common in nonobese children with obstructive sleep apnea compared to controls, and particularly in those who developed neurocognitive deficits. Neuro \- Partial complex seizures \- Anosmia Resp \- Obstructive sleep apnea \- Snoring Misc \- Hypersomnolence \- Restless movements during sleep Inheritance \- Autosomal dominant ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	APNEA, OBSTRUCTIVE SLEEP	c0520679	27,004	omim	https://www.omim.org/entry/107650	2019-09-22T16:44:57	{"doid": ["0050848"], "mesh": ["D020181"], "omim": ["107650"], "icd-9": ["327.23"], "icd-10": ["G47.33"], "synonyms": ["Alternative titles", "OSA", "OBSTRUCTIVE SLEEP APNEA SYNDROME", "SLEEP APNEA/HYPOPNEA SYNDROME"]}
A number sign (#) is used with this entry because of evidence that low density lipoprotein cholesterol level (LDLCQ7) is associated with variation in the NPC1L1 gene (608010) on chromosome 7p13. Description LDLCQ7 is a quantitative trait affecting LDL levels that is effected through the NPC1L1 gene, which is responsible for the intestinal absorption of cholesterol. NPC1L1 is the molecular target for the drug ezetimibe, and variants in this gene affect response to this drug. Clinical Features Cohen et al. (2006) used the nonsynonymous (NS) sequence variant technique to determine whether genetic variation in NPC1L1 contributes to variability in cholesterol absorption and plasma levels of low density lipoproteins. To estimate sterol absorption, they measured the ratio of campesterol to lathosterol (Ca:L ratio) in plasma, a high Ca:L ratio indicating a high rate of intestinal absorption of cholesterol, and a low Ca:L ration indicating a low absorption of cholesterol. In a study of 296 low absorbers and 296 high absorbers, equally divided by African American/white and male/female, from the Dallas Heart Study, nonsynonymous sequence variations in NPC1L1 were 5 times more common in low absorbers (26 individuals) than in high absorbers (5 individuals). The rare variants identified in low absorbers were found in 6% of 1,832 African Americans and were associated with lower plasma levels of LDL cholesterol (96 +/- 36 mg/dl vs 105 +/- 36 mg/dl; p = 0.005). The authors concluded that rare sequence variants in NPC1L1 are collectively associated with variations in sterol absorption and plasma levels of LDL-C. ### Response to Ezetimibe Ezetimibe is a selective cholesterol absorption inhibitor, which potently inhibits the uptake and absorption of biliary and dietary cholesterol from the small intestine without affecting the absorption of fat-soluble vitamins, triglycerides, or bile acids (summary by Davis et al., 2008). The NPC1L1 protein is the molecular target for ezetimibe. Pisciotta et al. (2007) investigated the response to ezetimibe monotherapy in 50 nongenotyped patients with a clinical diagnosis of primary hypercholesterolemia who were intolerant to statins. Patients showed wide interindividual variability, with decreases in plasma LDL-C ranging from -47.7% to -13.4%. Molecular Genetics ### Low Density Lipoprotein Levels Chen et al. (2009) screened the NPC1L1 gene in 50 Chinese individuals and identified a genomic -762C-T promoter polymorphism (rs2073548) that was found in 34% of individuals. Luciferase assay in the HepG2 cell line showed that the -762C allele had significantly higher promoter activity than -762T (3.5-fold, p = 0.05), and that NPC1L1 promoter activity was downregulated by cholesterol content in a dose-dependent manner in both genotypes. Association analysis in 224 Chinese individuals revealed that the -762C allele was associated with significantly higher serum total cholesterol and LDL-cholesterol content levels in a recessive model (p less than 0.05). Teslovich et al. (2010) performed a genomewide association study for plasma lipids in more than 100,000 individuals of European ancestry and reported 95 significantly associated loci (p = less than 5 x 10(-8)), with 59 showing genomewide significant association with lipid traits for the first time. The newly reported associations included SNPs near known lipid regulators (e.g., CYP7A1, 118455; NPC1L1; and SCARB1, 601040) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contributed not only to normal variation in lipid traits but also to extreme lipid phenotypes and had an impact on lipid traits in 3 non-European populations (East Asians, South Asians, and African Americans). The Myocardial Infarction Genetics Consortium Investigators (2014) sequenced the NPC1L1 gene in 7,364 patients with coronary heart disease and 14,728 controls without such disease who were of European, African, and South Asian ancestry and identified 15 distinct inactivating mutations. One in 650 persons was a carrier of such a mutation. Heterozygous carriers of NPC1L1 inactivating mutations had a mean LDL cholesterol level that was 12 mg per deciliter (0.31 mmol per liter) lower than that in noncarriers (p = 0.04). Carrier status was associated with a relative reduction of 53% in the risk of coronary heart disease (odds ratio for carriers, 0.47; 95% confidence interval, 0.25 to 0.87; p = 0.008). In total, only 11 of 29,954 patients with coronary heart disease had an inactivating mutation (carrier frequency, 0.04%) in contrast to 71 of 83,140 controls (carrier frequency, 0.09%). One such inactivating mutation (rs145297799) resulted in replacement of arginine-406 with a stop codon (R406X) (c.1216C-T, NM_013389.2). This variant was genotyped in a total of 26,507 patients with coronary heart disease and 75,654 controls. The carrier frequency was 0.02 in CHD patients (6 identified) and 0.06 in participants without CHD (49 identified). The R406X variant was seen only in individuals of European ancestry. Mirshahi and Carey (2015) followed up on the study of the Myocardial Infarction Genetics Consortium Investigators (2014) by investigating the Geisinger MyCode cohort. They identified 7 R406X carriers, all of European ancestry and none with CHD. They identified no carrier of an inactivating variant of NPC1L1 with CHD, as compared with 1,001 cases among noncarriers. Lipid levels were comparable among carriers and noncarriers, suggesting another cause for the protective effect. ### Response to Ezetimibe Wang et al. (2004) used the nonresponse phenotype of plasma LDL cholesterol to ezetimibe treatment to ascertain individuals who might have variant NPC1L1. Of 8 nonresponders, 1 was found to be a compound heterozygote for 2 rare nonsynonymous polymorphisms in NPC1L1 (see 608010.0001 and 608010.0002) that were absent in 278 normal controls. Simon et al. (2005) genotyped the NPC1L1 gene in hypercholesterolemic individuals from clinical trial cohorts and healthy individuals and found no association between NPC1L1 SNPs and baseline cholesterol level. Significant associations between LDL cholesterol response and treatment with ezetimibe were observed in 2 large clinical trials; the authors noted that the SNPs identified in this study were unlikely to represent causal variants, however, given that no single SNP was found to support the full magnitude of the effect. To investigate the variable response to ezetimibe monotherapy in 50 patients with a clinical diagnosis of primary hypercholesterolemia who were intolerant to statin therapy, Pisciotta et al. (2007) sequenced the NPC1L1 gene in the patients with the highest and the lowest responses. They found a higher prevalence of the G allele of the c.816C-G polymorphism (L272L) in hyperresponders. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	LOW DENSITY LIPOPROTEIN CHOLESTEROL LEVEL QUANTITATIVE TRAIT LOCUS 7	c4693795	27,005	omim	https://www.omim.org/entry/617966	2019-09-22T15:44:12	{"omim": ["617966"]}
A number sign (#) is used with this entry because of evidence that slow-channel congenital myasthenic syndrome-4A (CMS4A) is caused by heterozygous mutation in the CHRNE gene (100725) on chromosome 17p13. Biallelic CHRNE mutations have rarely been reported. Mutation in the CHRNE gene can also cause fast-channel CMS (CMS4B; 616324) and CMS with acetylcholine receptor (AChR) deficiency (CMS4C; 608931). Description Slow-channel congenital myasthenic syndrome (SCCMS) is a disorder of the postsynaptic neuromuscular junction (NMJ) characterized by early-onset progressive muscle weakness. The disorder results from kinetic abnormalities of the acetylcholine receptor channel, specifically from prolonged opening and activity of the channel, which causes prolonged synaptic currents resulting in a depolarization block. This is associated with calcium overload, which may contribute to subsequent degeneration of the endplate and postsynaptic membrane. Treatment with quinine, quinidine, or fluoxetine may be helpful; acetylcholinesterase inhibitors and amifampridine should be avoided (summary by Engel et al., 2015). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462). Clinical Features Oosterhuis et al. (1987) reported a young woman (case 2) who developed mild ptosis in her late teens and progressive muscle weakness in her twenties. AChR antibodies were absent, and there was no response to anticholinesterase medication. Electrophysiologic studies showed a prolonged rise and decay of miniature endplate potentials (MEPPs). Ultrastructural studies showed degeneration of junctional folds and diffusely thickened endplate basal lamina. Two asymptomatic first-degree relatives had similar abnormal electrophysiologic findings. The findings suggested prolonged open time of the ACh-induced ion channel, consistent with slow-channel myasthenic syndrome. Chauplannaz and Bady (1994) reported a woman (case 3) with SCCMS who had onset of symptoms in her twenties. She first noted weakness of the finger extensor muscles, and later developed weakness in other muscle groups, including the neck muscles. Single nerve stimulation elicited a repetitive compound muscle activation potential (CMAP) response, and repetitive nerve stimulation induced a myasthenic decremental response in finger extensor muscles. Her mother and son were similarly affected. Ohno et al. (1995) reported a 20-year-old woman with myasthenic symptoms since the neonatal period, a decremental electromyographic response on stimulation of motor nerves, negative tests for anti-AChR antibodies, and no history of similarly affected relatives. Studies of an intercostal muscle specimen from this patient at age 17 revealed signs of severe endplate myopathy, and patch-clamp studies showed markedly prolonged AChR channel openings. Engel et al. (1996) reported a 16-year-old boy with slow-channel congenital myasthenic syndrome. He had myasthenic symptoms since early infancy involving ocular, truncal, and limb muscles. He also experienced intermittent episodes of respiratory insufficiency requiring ventilatory support. Electrophysiologic studies showed prolonged endplate currents and prolonged AChR channel-opening episodes, and muscle biopsy showed endplate myopathy with loss of AChR from degenerating junctional folds. Croxen et al. (2002) reported a rare example of a patient, born to consanguineous parents, with autosomal recessive inheritance of SCCMS. She presented at age 29 years with failure to breathe after administration of an anesthetic. She had bilateral ptosis, limitation of eye movements, and weakness of facial, neck, shoulder, hip, and small muscles of the hand. She first became aware of weakness in her early twenties. Electrophysiologic studies showed a decremental response to repetitive stimulations, consistent with a defect in neuromuscular transmission. Molecular Genetics In a patient with SCCMS, Ohno et al. (1995) identified a heterozygous missense mutation in the CHRNE gene (T264P; 100725.0001) that resulted in prolonged channel opening. In a 16-year-old boy with SCCMS, Engel et al. (1996) identified a heterozygous missense mutation in the CHRNE gene (L269F; 100725.0002). Croxen et al. (2002) reported 2 unrelated families with a mild form of SCCMS confirmed by heterozygous missense mutation in the CHRNE gene (L221F; 100725.0010). In 1 family, all members with the mutation were affected, whereas in the other family, 2 members with the mutation were clinically unaffected, indicating incomplete penetrance. The patients had previously been reported by Oosterhuis et al. (1987) and Chauplannaz and Bady (1994). In a patient, born of consanguineous parents, with SCCMS, Croxen et al. (2002) identified compound heterozygous mutations in the CHRNE gene (100725.0022-100725.0023). Animal Model Kraner et al. (2002) determined the genetic defect in 4 previously reported related Brahman calves with severe myasthenia weakness (Thompson, 1998). They demonstrated homozygosity for a 20-bp deletion in exon 5 of the CHRNE gene that caused a frameshift followed by a premature stop codon. Survival was limited to only a few months, indicating that the effect on neuromuscular transmission was more pronounced in the calves than that observed in humans homozygous for truncating CHRNE mutations. Kraner et al. (2002) speculated that this might be due to a different capacity to express the fetal-type AChR after birth. Cossins et al. (2004) generated transgenic mice that constitutively expressed Chrng (100730) in a Chrne-knockout background. These mice, in which neuromuscular transmission is mediated by fetal AChR, lived well into adulthood but showed striking similarities to human AChR deficiency syndrome. Mutant mice displayed fatigable muscle weakness, reduced MEPPs and endplate potentials, reduced motor endplate AChR number, and altered endplate morphology. Groshong et al. (2007) found that mice with the L269F mutation in the Chrne gene (100725.0002) showed muscle weakness, fatigability, and impaired neuromuscular transmission, similar to the human disorder. Muscle fibers from mutant mice showed significantly increased levels of the calcium-activated cysteine protease calpain (see, e.g., CAPN3; 114240) at the NMJ. Calpain levels were dependent on synaptic activity and activation of mutant AChR, and diminished with blockade of AChR. Transgenic expression of the natural calpain inhibitor calpastatin (CAST; 114090) reduced calpain to baseline, normalized the size of the NMJ and the endplate current frequency, and improved strength and neuromuscular transmission. The protective effect of Cast appeared to be due to a strengthening of synaptic connections, rather than a protective effect on mutant AChRs. There was persistent endplate myopathy in Cast-null/L269F double-mutant mice associated with ongoing activation of caspase family proteases, such as Casp3 (600636), that are not inhibited by calpastatin. INHERITANCE \- Autosomal dominant \- Autosomal recessive (rare) HEAD & NECK Eyes \- Ptosis \- Ophthalmoparesis RESPIRATORY \- Respiratory insufficiency due to muscle weakness (in some patients) ABDOMEN Gastrointestinal \- Poor feeding due to muscle weakness \- Poor suck \- Dysphagia MUSCLE, SOFT TISSUES \- Generalized hypotonia due to defect at the neuromuscular junction \- Limb muscle weakness \- Bulbar muscle weakness \- Easy fatigability \- Decremental compound muscle action potential (CMAP) response to repetitive nerve stimulation \- Repetitive response to single nerve stimulation \- Prolonged rise and decay of miniature endplate potentials (MEPP) \- Endplate myopathy \- Degeneration of junctional folds MISCELLANEOUS \- Variable age at onset (range infancy to young adult) \- Poor response to acetylcholinesterase inhibitors \- Most cases are autosomal dominant, recessive inheritance has rarely been reported MOLECULAR BASIS \- Caused by mutation in the cholinergic receptor, nicotinic, epsilon polypeptide gene (CHRNE, 100725.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	MYASTHENIC SYNDROME, CONGENITAL, 4A, SLOW-CHANNEL	c0751882	27,006	omim	https://www.omim.org/entry/605809	2019-09-22T16:10:59	{"doid": ["0110678"], "mesh": ["D020294"], "omim": ["605809"], "orphanet": ["98913", "590"], "synonyms": ["CMS Ia1, FORMERLY", "Alternative titles", "CONGENITAL MYASTHENIC SYNDROME TYPE Ia1, FORMERLY"], "genereviews": ["NBK1168"]}
Breast cancer is a disease in which certain cells in the breast become abnormal and multiply uncontrollably to form a tumor. Although breast cancer is much more common in women, this form of cancer can also develop in men. In both women and men, the most common form of breast cancer begins in cells lining the milk ducts (ductal cancer). In women, cancer can also develop in the glands that produce milk (lobular cancer). Most men have little or no lobular tissue, so lobular cancer in men is very rare. In its early stages, breast cancer usually does not cause pain and may exhibit no noticeable symptoms. As the cancer progresses, signs and symptoms can include a lump or thickening in or near the breast; a change in the size or shape of the breast; nipple discharge, tenderness, or retraction (turning inward); and skin irritation, dimpling, redness, or scaliness. However, these changes can occur as part of many different conditions. Having one or more of these symptoms does not mean that a person definitely has breast cancer. In some cases, cancerous tumors can invade surrounding tissue and spread to other parts of the body. If breast cancer spreads, cancerous cells most often appear in the bones, liver, lungs, or brain. Tumors that begin at one site and then spread to other areas of the body are called metastatic cancers. A small percentage of all breast cancers cluster in families. These cancers are described as hereditary and are associated with inherited gene mutations. Hereditary breast cancers tend to develop earlier in life than noninherited (sporadic) cases, and new (primary) tumors are more likely to develop in both breasts. ## Frequency Breast cancer is the second most commonly diagnosed cancer in women. (Only skin cancer is more common.) About one in eight women in the United States will develop invasive breast cancer in her lifetime. Researchers estimate that more than 276,000 new cases of invasive breast cancer will be diagnosed in U.S. women in 2020. Male breast cancer represents less than 1 percent of all breast cancer diagnoses. Scientists estimate that about 2,600 new cases of breast cancer will be diagnosed in men in 2020. Particular gene mutations associated with breast cancer are more common among certain geographic or ethnic groups, such as people of Ashkenazi (central or eastern European) Jewish heritage and people of Norwegian, Icelandic, or Dutch ancestry. ## Causes Cancers occur when a buildup of mutations in critical genes—those that control cell growth and division or repair damaged DNA—allow cells to grow and divide uncontrollably to form a tumor. In most cases of breast cancer, these genetic changes are acquired during a person's lifetime and are present only in certain cells in the breast. These changes, which are called somatic mutations, are not inherited. Somatic mutations in many different genes have been found in breast cancer cells. Less commonly, gene mutations present in essentially all of the body's cells increase the risk of developing breast cancer. These genetic changes, which are classified as germline mutations, are usually inherited from a parent. In people with germline mutations, changes in other genes, together with environmental and lifestyle factors, also influence whether a person will develop breast cancer. Some breast cancers that cluster in families are associated with inherited mutations in particular genes, such as BRCA1 or BRCA2. These genes are described as "high penetrance" because they are associated with a high risk of developing breast cancer and ovarian cancer and a moderate risk of developing pancreatic cancer and a type of skin cancer called melanoma in women who have mutations. Men with mutations in these genes also have an increased risk of developing several forms of cancer, including breast cancer, pancreatic cancer, prostate cancer, and melanoma. The proteins produced from the BRCA1 and BRCA2 genes are involved in fixing damaged DNA, which helps to maintain the stability of a cell's genetic information. They are described as tumor suppressors because they help keep cells from growing and dividing too fast or in an uncontrolled way. Mutations in these genes impair DNA repair, allowing potentially damaging mutations to persist in DNA. As these defects accumulate, they can trigger cells to grow and divide without control or order to form a tumor. A significantly increased risk of breast cancer is also a feature of several rare genetic syndromes. These include Cowden syndrome, which is most often caused by mutations in the PTEN gene; hereditary diffuse gastric cancer, which results from mutations in the CDH1 gene; Li-Fraumeni syndrome, which is usually caused by mutations in the TP53 gene; and Peutz-Jeghers syndrome, which typically results from mutations in the STK11 gene. The proteins produced from these genes act as tumor suppressors. Mutations in any of these genes can allow cells to grow and divide unchecked, leading to the development of a cancerous tumor. Like BRCA1 and BRCA2, these genes are considered "high penetrance" because mutations greatly increase a person's chance of developing cancer. In addition to breast cancer, mutations in these genes increase the risk of several other types of cancer over a person's lifetime. Some of the conditions also include other signs and symptoms, such as the growth of noncancerous (benign) tumors. Mutations in dozens of other genes have been studied as possible risk factors for breast cancer. These genes are described as "low penetrance" or "moderate penetrance" because changes in each of these genes appear to make only a small or moderate contribution to overall breast cancer risk. Some of these genes provide instructions for making proteins that interact with the proteins produced from the BRCA1 or BRCA2 genes. Others act through different pathways. Researchers suspect that the combined influence of variations in these genes may significantly impact a person's risk of developing breast cancer. In many families, the genetic changes associated with hereditary breast cancer are unknown. Identifying additional genetic risk factors for breast cancer is an active area of medical research. In addition to genetic changes, researchers have identified many personal and environmental factors that contribute to a person's risk of developing breast cancer. These factors include sex, age, ethnic background, a history of previous breast cancer, certain changes in breast tissue, and hormonal and reproductive factors. A history of breast cancer in closely related family members is also an important risk factor, particularly if the cancer occurred in early adulthood. ### Learn more about the genes associated with Breast cancer * ATM * BRCA1 * BRCA2 * CDH1 * CYP19A1 * FGFR2 * H19 * MAP3K1 * NBN * PTEN * RAD51 * STK11 * TERT * TP53 Additional Information from NCBI Gene: * BARD1 * BRIP1 * CASP8 * CHEK2 * CTLA4 * LSP1 * MRE11 * PALB2 * RAD51C * TOX3 * XRCC2 * XRCC3 ## Inheritance Pattern Most cases of breast cancer are not caused by inherited genetic factors. These cancers are associated with somatic mutations in breast cells that are acquired during a person's lifetime, and they do not cluster in families. In hereditary breast cancer, the way that cancer risk is inherited depends on the gene involved. For example, mutations in the BRCA1 and BRCA2 genes are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase a person's chance of developing cancer. Although breast cancer is more common in women than in men, the mutated gene can be inherited from either the mother or the father. In the other syndromes discussed above, the gene mutations that increase cancer risk also have an autosomal dominant pattern of inheritance. It is important to note that people inherit an increased likelihood of developing cancer, not the disease itself. Not all people who inherit mutations in these genes will ultimately develop cancer. In many cases of breast cancer that clusters in families, the genetic basis for the disease and the mechanism of inheritance are unclear. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Breast cancer	c1861906	27,007	medlineplus	https://medlineplus.gov/genetics/condition/breast-cancer/	2021-01-27T08:25:23	{"gard": ["10415", "10804"], "mesh": ["C566178"], "omim": ["114480", "604370", "612555"], "synonyms": []}
X-linked congenital generalized hypertrichosis is a rare congenital (present at birth) skin disease. It is characterized by hair overgrowth on the entire body in males, and mild and asymmetric hair overgrowth in females. It is associated with mild facial abnormalities (including nasal openings that are tipped upwards and moderate protrusion of the jaw) and occasional teeth anomalies and deafness. It is caused by a specific abnormality of the X chromosome. Inheritance is X-linked. It is important to know if the disease occurs alone (is an isolated form), or if it is part of a genetic syndrome. Treatment includes standard methods for hair removal such as shaving, laser hair removal, electrolysis, chemical methods and 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	X-linked congenital generalized hypertrichosis	c1855900	27,008	gard	https://rarediseases.info.nih.gov/diseases/2863/x-linked-congenital-generalized-hypertrichosis	2021-01-18T17:57:03	{"mesh": ["C538388"], "omim": ["307150"], "orphanet": ["79495"], "synonyms": ["CGH", "HTC2", "Macias Flores-Garcia Cruz-Rivera syndrome", "HCG", "Chromosome Xq27.1 interchromosomal insertion syndrome", "Congenital generalized hypertrichosis, Macias-Flores type", "Macias-Flores Garcia-Cruz Rivera syndrome", "Hypertrichosis congenital generalized X-linked"]}
A rare, genetic, syndromic intellectual disability characterised by several dysmorphic features, hypotonia, developmental delay, intellectual disability, behavioral problems, visual and hearing abnormalities, constipation, and feeding difficulties. Common dysmorphic features include coarse facies, broad forehead, synophrys, bushy eyebrows, deep-set eyes, downslanting palpebral fissures, epicanthus, depressed nasal bridge, bulbous nasal tip, posteriorly rotated ears, full cheeks, thin upper lip, inverted nipples, and hirsutism. Behavioral problems tend to be dominated by ADHD, but anxiety, aggressive outbursts and autistic features may also present. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	WAC-related facial dysmorphism-developmental delay-behavioral abnormalities syndrome	c4225239	27,009	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=466943	2021-01-23T19:12:29	{"omim": ["616708"]}
A rare, genetic, dermis disorder characterized by bilateral, fairly symmetrical, antecubital webbing extending from distal third of humerus to proximal third of forearm, associated with musculoskeletal abnormalities (i.e. absent long head of triceps, bilateral posterior dislocation of the radial head and hypoplasia of the olecranon processes) and absent skin creases over the terminal interphalangeal joints of fingers, clinically manifesting with moderate to severe elbow extension and supination limitation. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Antecubital pterygium syndrome	c1867439	27,010	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2987	2021-01-23T17:29:46	{"gard": ["4570"], "mesh": ["C566738"], "omim": ["178200"], "umls": ["C1867439"]}
A number sign (#) is used with this entry because of evidence that familial partial lipodystrophy-6 (FPLD6) is caused by homozygous mutation in the LIPE gene (151750) on chromosome 19q13. For a general phenotypic description and a discussion of genetic heterogeneity of familial partial lipodystrophy (FPLD), see 151660. Description Familial partial lipodystrophy-6 (FPLD6) is characterized by abnormal subcutaneous fat distribution, with variable excess accumulation of fat in the face, neck, shoulders, axillae, back, abdomen, and pubic region, and reduction in subcutaneous fat of the lower extremities. Progressive adult-onset myopathy is seen in some patients, and there is variable association with diabetes, hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, and hepatic steatosis (Zolotov et al., 2017). Clinical Features Carboni et al. (2014) described a sister and brother, born of consanguineous Italian parents, who had partial lipodystrophy associated with muscular dystrophy. The sister, who had had menstrual irregularity from youth, developed abnormal subcutaneous fat distribution at age 33 years, with accumulation in the neck, abdomen, and axillae, and progressive reduction of subcutaneous fat in the legs. She was diagnosed with diabetes at age 43, and examination at 50 years of age showed abnormal fat accumulation in the neck, abdomen, clavicular regions, axillae, labia majora, back, and area below the triceps, with concomitant reduction of subcutaneous fat in the legs. The patient also exhibited mild proximal muscle weakness involving both shoulder and hip girdle muscles. Her 49-year-old brother also had fat distribution anomalies, with increased subcutaneous adipose tissue of the abdomen and axillae and reduced subcutaneous fat in the legs. His muscle strength was normal. Both sibs had high levels of creatine kinase, and the sister also had elevated levels of triglycerides and cholesterol. Muscle biopsy from the sister showed dystrophic changes but normal immunohistochemical labeling of the proteins responsible for most common muscular dystrophies; trichome and oxidative stains revealed no evidence of mitochondrial disease. MRI in the sister showed fat accumulation in the neck, back, and abdomen; reduced subcutaneous fat in the lower limbs; and hepatic steatosis. Increased T2 signal was seen in the posterior thigh muscle and tibialis anterior and posterior, extensor digitorum longus, and soleus muscles. The brother's MRI showed nonhomogeneous subcutaneous fat distribution, with fat predominance in the anterior abdomen and reduced fat in the lower limbs; T2 signal was increased in the posterior leg muscle. Zolotov et al. (2017) reported a 41-year-old woman and her 36-year-old brother, from a consanguineous Israeli Arab family, who exhibited marked symmetric accumulation of subcutaneous fat in the face, neck, axillae, and trunk, with loss of subcutaneous fat from the lower extremities and progressive symmetric myopathy during adulthood. In addition, the sister had diabetes and the brother had hepatic steatosis. A 23-year-old younger brother reported muscle wasting of his lower extremities and recent difficulty climbing stairs, but his body fat distribution appeared to be normal. All 3 affected sibs had mild to severe hypertriglyceridemia, low levels of high-density lipoprotein cholesterol, and mildly elevated aminotransferase and uric acid levels with consistently high creatine kinase levels, compared to their 6 unaffected sibs. Inheritance Carboni et al. (2014) studied an Italian sister and brother with partial lipodystrophy associated with muscular dystrophy. The authors stated that, given the patients' parental consanguinity and discordant genders, the likely mode of inheritance was autosomal recessive. Molecular Genetics Albert et al. (2014) sequenced 12 lipolytic-pathway genes in 24 Old Order Amish individuals whose fasting serum triglyceride levels were at the extremes of the distribution, and detected a 19-bp deletion in the LIPE gene (151750.0001) in an individual whose triglyceride level was at the upper extreme. Genotyping for the LIPE deletion in 2,738 participants in the Amish Complex Disease Research program identified 1 individual who was homozygous for the deletion ('DD' genotype) and 140 heterozygotes; thus, 5.1% of the Amish persons carried the deletion compared with 0.2% of non-Amish persons of European descent. Three of the 9 sibs of the proband were also homozygous for the deletion. All 4 sibs exhibited impaired lipolysis and altered metabolic traits, including systemic insulin resistance and diabetes. Association analyses showed that heterozygous carriers of the deletion had an increased risk of dyslipidemia, with elevated triglycerides and reduced levels of high-density lipoprotein (HDL) cholesterol, hepatic steatosis, systemic insulin resistance, and diabetes. All 4 homozygous sibs received a diagnosis of type 2 diabetes (T2D; 125853) before 50 years of age, and heterozygous carriers had a risk of T2D that was 1.8 times that of noncarriers. In addition, MRI in a homozygous sib showed evidence for redistribution of body fat, with an increase in visceral fat and a decrease in subcutaneous fat of the extremities, resulting in a significant increase in the abdominal-to-calf subcutaneous fat ratio compared to a noncarrier sib. Adipose tissue from 2 of the homozygous sibs showed absence of hormone-sensitive lipase, small adipocytes, impaired lipolysis, insulin resistance, and inflammation. Transcription factors responsive to PPARG (601487) and downstream target genes were downregulated in their adipose tissue, altering the regulation of pathways influencing adipogenesis, insulin sensitivity, and lipid metabolism. In an Italian sister and brother from a consanguineous family with a late-onset form of partial lipodystrophy, originally reported by Carboni et al. (2014), Farhan et al. (2014) performed genomewide autozygosity mapping and whole-exome sequencing, and identified a frameshift mutation in the LIPE gene (151750.0002) that segregated with disease in the family. The mutation was not found in the NCBI dbSNP, 1000 Genomes Project, Human Gene Mutation, or Exome Variant Server databases, or in in-house control exomes. In an Israeli Arab sister and brother with multiple symmetric lipomatosis, partial lipodystrophy, and myopathy, Zolotov et al. (2017) performed Sanger and exome sequencing and identified homozygosity for a nonsense mutation in the LIPE gene (E1035X; 151750.0003) that segregated with disease in the family. The authors concluded that LIPE deficiency in humans is associated with adult-onset progressive multiple symmetric lipomatosis, lower extremity lipodystrophy, and myopathy, along with metabolic abnormalities such as diabetes, hypertriglyceridemia, and hepatic steatosis. ### Exclusion Studies In a sister and brother from a consanguineous Italian family with partial lipodystrophy associated with muscular dystrophy, Carboni et al. (2014) analyzed 13 known lipodystrophy-associated genes and found no pathogenic mutations. Respiratory chain enzyme dose and sequencing of whole mitochondrial DNA were normal, and SNP array analysis excluded copy number variations of pathogenic relevance shared between the sibs. INHERITANCE \- Autosomal recessive HEAD & NECK Neck \- Abnormal fat accumulation in neck CHEST Ribs Sternum Clavicles & Scapulae \- Abnormal fat accumulation in the clavicular regions (in some patients) ABDOMEN External Features \- Increased visceral fat Liver \- Hepatic steatosis GENITOURINARY External Genitalia (Female) \- Abnormal fat accumulation in the labia majora (in some patients) MUSCLE, SOFT TISSUES \- Abnormal subcutaneous fat distribution \- Reduced lower limb subcutaneous fat \- Abnormal fat accumulation in axillae (in some patients) \- Abnormal fat accumulation in the back (in some patients) \- Abnormal fat accumulation below the triceps (in some patients) \- Proximal muscle weakness, mild, of shoulder and hip girdle muscles (in some patients) \- Muscular dystrophy (in some patients) \- Increased T-2 signal in muscles of lower extremities on MRI (in some patients) METABOLIC FEATURES \- Dyslipidemia \- Elevated fasting triglycerides \- Low high-density lipoprotein cholesterol \- Small adipocytes \- Impaired lipolysis \- Macrophage infiltration of white adipose tissue ENDOCRINE FEATURES \- Elevated fasting glucose \- Elevated insulin \- Insulin resistance \- Type 2 diabetes mellitus \- Elevated serum adiponectin LABORATORY ABNORMALITIES \- Elevated creatine kinase (in some patients) MISCELLANEOUS \- Heterozygous carriers have an increased risk of metabolic dysfunction MOLECULAR BASIS \- Caused by mutation in the hormone-sensitive lipase gene (LIPE, 151750.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	LIPODYSTROPHY, FAMILIAL PARTIAL, TYPE 6	c4014869	27,011	omim	https://www.omim.org/entry/615980	2019-09-22T15:50:25	{"doid": ["0070206"], "omim": ["615980"], "orphanet": ["435660"], "synonyms": ["LIPE-related FPLD", "FPLD6", "Alternative titles", "LIPODYSTROPHY, FAMILIAL PARTIAL, ASSOCIATED WITH LIPE MUTATIONS"]}
A rare genetic glomerular disease characterized by variably severe nephropathy with microscopic hematuria and proteinuria, in the absence of nail and bone abnormalities. Characteristic ultrastructural findings are irregular thickening and moth-eaten appearance of the glomerular basement membrane with focal deposition of type III collagen fibrils. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Nail-patella-like renal disease	c0403548	27,012	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2613	2021-01-23T18:30:01	{"gard": ["321"], "mesh": ["C537228"], "omim": ["256020"], "umls": ["C0403548"], "synonyms": ["Salcedo syndrome"]}
Bethlem myopathy is a rare disease affecting the skeletal muscles and connective tissue. The disease is characterized by slowly progressive muscle weakness and joint stiffness (contractures). It most often affects the fingers, wrists, elbows, and ankles. Signs and symptoms may begin before birth (with decreased fetal movements), shortly after birth (with low muscle tone or torticollis), in early childhood (with delayed motor skills, muscle weakness, and contractures), or in adulthood (with weakness, Achilles tendon, or finger contractures). Due to the disease's progression, most people with Bethlem myopathy over age 50 require mobility aids (such as a cane, crutches, or wheelchair) for outdoor mobility. Rarely, severe muscle weakness may lead to respiratory difficulties in later life. Bethlem myopathy is caused by mutations (changes) in the COL6A1, COL6A2, or COL6A3 genes. Most cases are inherited in an autosomal dominant manner, but in rare cases the disease is autosomal recessive. The diagnosis is based on clinical examination and laboratory tests, but genetic testing may confirm the diagnosis. Treatment depends on individual symptoms but routinely involves physical therapy. Surgery to correct joint contractures may be needed. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Bethlem myopathy	c1834674	27,013	gard	https://rarediseases.info.nih.gov/diseases/873/bethlem-myopathy	2021-01-18T18:01:49	{"mesh": ["C535436"], "omim": ["158810"], "umls": ["C1834674"], "orphanet": ["610"], "synonyms": ["Myopathy, benign congenital, with contractures", "Muscular dystrophy, benign congenital"]}
A number sign (#) is used with this entry because X-linked isolated hypospadias-2 (HYSP2) can be caused by mutation in the MAMLD1 gene (300120) on chromosome Xq28. For a phenotypic description and a discussion of genetic heterogeneity of hypospadias, see 300633. Clinical Features Hypospadias is a common malformation in which the urethra opens on the ventral side of the penis (Fukami et al., 2006). Molecular Genetics Fukami et al. (2006) performed direct sequencing of the coding exons 3-6 of the CXORF6 (MAMLD1) gene and their flanking splice sites in 166 individuals with various types of 46,XY disorders of sex development. They identified 3 nonsense mutations (300120.0001-300120.0003) in 4 Japanese individuals with penoscrotal hypospadias as the conspicuous phenotype. The mutations were predicted to cause nonsense-mediated mRNA decay because of their positions. Consistent with this, RT-PCR for leukocytes indicated markedly reduced transcripts. All affected individuals had seemingly normal pituitary-gonadal serum hormone levels. INHERITANCE \- X-linked recessive GENITOURINARY External Genitalia (Male) \- Hypospadias, penoscrotal MISCELLANEOUS \- See also autosomal form, 146450 , and another X-linked form, 300633 MOLECULAR BASIS \- Caused by mutation in the mastermind-like domain containing 1 gene (MAMLD1, 300120.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	HYPOSPADIAS 2, X-LINKED	c2677879	27,014	omim	https://www.omim.org/entry/300758	2019-09-22T16:19:36	{"doid": ["10892"], "mesh": ["C567462"], "omim": ["300758"], "orphanet": ["95706"], "synonyms": ["Perineal, scrotal or penoscrotal hypospadias"]}
Pelvic venous disease Other namesPelvic congestion syndrome A very large (9cm) fibroid of the uterus which is causing pelvic congestion syndrome as seen on X-ray computed tomography Specialty[Interventional Radiology], gynecology SymptomsChronic pelvic pain[1] Diagnostic methodUltrasound, CT scan, MRI, laparoscopy[1] MedicationMedroxyprogesterone, nonsteroidal anti-inflammatory drugs (NSAIDs)[1] Frequency30% of women[2] Pelvic congestion syndrome, also known as pelvic vein incompetence, is a long term condition in women believed to be due to enlarged veins in the lower abdomen.[1][3] The condition may cause chronic pain, such as a constant dull ache, which can be worsened by standing or sex.[1] Pain in the legs or lower back may also occur.[1] While the condition is believed to be due to blood flowing back into pelvic veins as a result of faulty valves in the veins, this hypothesis is not certain.[3] The condition may occur or worsen during pregnancy.[1] The presence of estrogen is believed to be involved in the mechanism.[1] Diagnosis may be supported by ultrasound, CT scan, MRI, or laparoscopy.[1] Early treatment options include medroxyprogesterone or nonsteroidal anti-inflammatory drugs (NSAIDs).[1] Surgery to block the varicose veins may also be done.[1] About 30% of women of reproductive age are affected.[2] It is believed to be the cause of about a third of chronic pelvic pain cases.[4] While pelvic venous insufficiency was identified in the 1850s it was only linked with pelvic pain in the 1940s.[4] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 4 Treatment * 5 See also * 6 References * 7 External links ## Signs and symptoms[edit] Women with this condition experience a constant pain that may be dull and aching, but is occasionally more acute. The pain is worse at the end of the day and after long periods of standing, and sufferers get relief when they lie down. The pain is worse during or after sexual intercourse, and can be worse just before the onset of the menstrual period.[5] Women with pelvic congestion syndrome have a larger uterus and a thicker endometrium. 56% of women manifest cystic changes to the ovaries,[6] and many report other symptoms, such as dysmenorrhea, back pain, vaginal discharge, abdominal bloating, mood swings or depression, and fatigue.[5] ## Causes[edit] 1. Local pelvic hormonal melieu 2. Venous outflow obstruction, such as May-Thurner syndrome, Nutcracker syndrome, Budd-Chiari syndrome, or left renal vein thrombosis 3. External compression due to tumor (including fibroids, endometriosis), or scarring [7] ## Diagnosis[edit] A very large (9cm) fibroid of the uterus which is causing pelvic congestion syndrome as seen on ultrasound Diagnosis can be made using ultrasound or laparoscopy testing. The condition can also be diagnosed with a venogram, CT scan, or an MRI. Ultrasound is the diagnostic tool most commonly used.[5] Some research has suggested that transvaginal duplex ultrasound is the best test for pelvic venous reflux.[8] ## Treatment[edit] Early treatment options include pain medication using nonsteroidal anti-inflammatory drugs,[5] and suppression of ovarian function.[6] More advanced treatment includes a minimally invasive procedure performed by an Interventional Radiologist. This minimally invasive procedure involves stopping blood within the pelvic varicose veins using a minimally invasive procedure called a catheter directed embolization. The procedure rarely requires an overnight stay in hospital and is usually performed as an outpatient procedure, and is done using local anesthetic and moderate sedation.[9] Patients report an 80% success rate, as measured by the amount of pain reduction experienced.[9] ## See also[edit] * Ovarian vein syndrome * Nutcracker syndrome ## References[edit] 1. ^ a b c d e f g h i j k "Pelvic Congestion Syndrome - Women's Health Issues". Merck Manuals Consumer Version. Retrieved 27 September 2019. 2. ^ a b Cheema, Omer Saadat; Singh, Pramvir (2020). "Pelvic Congeston Syndrome". Statpearls. PMID 32809625. Text was copied from this source, which is available under a Creative Commons Attribution 4.0 International License. 3. ^ a b Champaneria, R; Shah, L; Moss, J; Gupta, JK; Birch, J; Middleton, LJ; Daniels, JP (January 2016). "The relationship between pelvic vein incompetence and chronic pelvic pain in women: systematic reviews of diagnosis and treatment effectiveness". Health Technology Assessment (Winchester, England). 20 (5): 1–108. doi:10.3310/hta20050. PMC 4781546. PMID 26789334. 4. ^ a b Brown, CL; Rizer, M; Alexander, R; Sharpe EE, 3rd; Rochon, PJ (March 2018). "Pelvic Congestion Syndrome: Systematic Review of Treatment Success". Seminars in Interventional Radiology. 35 (1): 35–40. doi:10.1055/s-0038-1636519. PMC 5886772. PMID 29628614. 5. ^ a b c d "Dysmenorrhea". Merck Online Medical Manual. December 2008. Retrieved December 23, 2010. 6. ^ a b Phillip Reginald, MD. "Pelvic Congestion" (PDF). The International Pelvic Pain Society. Retrieved December 23, 2010. 7. ^ Rutherford's vascular surgery references. [S.l.]: Elsevier Saunders. 2014. ISBN 978-0323243056. 8. ^ Whiteley M, Dos Santos S, Harrison C, Holdstock J, Lopez A (Oct 2014). "Transvaginal duplex ultrasonography appears to be the gold standard investigation for the haemodynamic evaluation of pelvic venous reflux in the ovarian and internal iliac veins in women". Phlebology. 30 (10): 706–13. doi:10.1177/0268355514554638. PMID 25324278. S2CID 25053851. 9. ^ a b "Pelvic Pain (Pelvic Congestion Syndrome)". Johns Hopkins. Retrieved December 23, 2010. ## External links[edit] Classification D * ICD-9-CM: 625.5 * v * t * e Female diseases of the pelvis and genitals Internal Adnexa Ovary * Endometriosis of ovary * Female infertility * Anovulation * Poor ovarian reserve * Mittelschmerz * Oophoritis * Ovarian apoplexy * Ovarian cyst * Corpus luteum cyst * Follicular cyst of ovary * Theca lutein cyst * Ovarian hyperstimulation syndrome * Ovarian torsion Fallopian tube * Female infertility * Fallopian tube obstruction * Hematosalpinx * Hydrosalpinx * Salpingitis Uterus Endometrium * Asherman's syndrome * Dysfunctional uterine bleeding * Endometrial hyperplasia * Endometrial polyp * Endometriosis * Endometritis Menstruation * Flow * Amenorrhoea * Hypomenorrhea * Oligomenorrhea * Pain * Dysmenorrhea * PMS * Timing * Menometrorrhagia * Menorrhagia * Metrorrhagia * Female infertility * Recurrent miscarriage Myometrium * Adenomyosis Parametrium * Parametritis Cervix * Cervical dysplasia * Cervical incompetence * Cervical polyp * Cervicitis * Female infertility * Cervical stenosis * Nabothian cyst General * Hematometra / Pyometra * Retroverted uterus Vagina * Hematocolpos / Hydrocolpos * Leukorrhea / Vaginal discharge * Vaginitis * Atrophic vaginitis * Bacterial vaginosis * Candidal vulvovaginitis * Hydrocolpos Sexual dysfunction * Dyspareunia * Hypoactive sexual desire disorder * Sexual arousal disorder * Vaginismus * Urogenital fistulas * Ureterovaginal * Vesicovaginal * Obstetric fistula * Rectovaginal fistula * Prolapse * Cystocele * Enterocele * Rectocele * Sigmoidocele * Urethrocele * Vaginal bleeding * Postcoital bleeding Other / general * Pelvic congestion syndrome * Pelvic inflammatory disease External Vulva * Bartholin's cyst * Kraurosis vulvae * Vestibular papillomatosis * Vulvitis * Vulvodynia Clitoral hood or clitoris * Persistent genital arousal disorder [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Pelvic congestion syndrome	c0152078	27,015	wikipedia	https://en.wikipedia.org/wiki/Pelvic_congestion_syndrome	2021-01-18T18:50:44	{"umls": ["C0152078"], "wikidata": ["Q7161793"]}
Species of plant-infecting bacterium This article includes a list of general references, but it remains largely unverified because it lacks sufficient corresponding inline citations. Please help to improve this article by introducing more precise citations. (April 2009) (Learn how and when to remove this template message) Fire blight Scientific classification Domain: Bacteria Phylum: Proteobacteria Class: Gammaproteobacteria Order: Enterobacterales Family: Erwiniaceae Genus: Erwinia Species: E. amylovora Binomial name Erwinia amylovora (Burrill 1882) Winslow et al. 1920 Type strain = NCPPB 683 Fire blight, also written fireblight, is a contagious disease affecting apples, pears, and some other members of the family Rosaceae. It is a serious concern to apple and pear producers. Under optimal conditions, it can destroy an entire orchard in a single growing season. The causal pathogen is Erwinia amylovora,[1] a Gram-negative bacterium in the order Enterobacterales. Pears are the most susceptible, but apples, loquat, crabapples, quinces, hawthorn, cotoneaster, Pyracantha, raspberry and some other rosaceous plants are also vulnerable. The disease is believed to be indigenous to North America, from where it spread to most of the rest of the world. Fire blight is not believed to be present in Australia though it might possibly exist there.[2] It has been a major reason for a long-standing embargo on the importation of New Zealand apples to Australia.[3] Japan was likewise believed to be without the disease, but it was discovered in pears grown in northern Japan. Japanese authorities are, however, still denying its existence, and the Japanese scientist who discovered it is believed to have committed suicide after his name was leaked to affected farmers.[4] In Europe it is listed as a quarantine disease, and has been spreading along Hawthorn (Crataegus) hedges planted alongside railways, motorways and main roads. ## Contents * 1 History * 2 Symptoms * 3 Dissemination * 4 Management * 5 Importance * 6 Pathogenesis * 7 References * 8 External links ## History[edit] In the early 1800s, E. amylovara was the first bacterium that could be used in experiments to demonstrate that it did indeed cause disease in plants.[citation needed][clarification needed] It is accepted[by whom?] that this destructive crop bacterium had initially originated in North America. Today, E. amylovara can currently be found in all the provinces of Canada, as well as in some parts of the United States of America; states include Alabama, California, Colorado, Connecticut, Georgia, Illinois, Maine, Maryland, Massachusetts, Michigan, New York, North Carolina, Ohio, Oregon, Pennsylvania, Texas, Utah, Virginia, Washington, West Virginia and Wisconsin. Other American countries of its occurrence include but are not limited to Mexico and Bermuda. On the African continent, E. amylovora has been confirmed in Egypt. It is believed that the pathogen was first introduced into Northern Europe through bacterial ooze from fruit containers in the 1950s[citation needed], imported from Northern America. During the 1950s-1960's, E. amylovora had spread through much of Northern Europe, yet leaving large areas of Germany and France seemingly untouched by the disease of which the bacteria cause a devastating disease known as "fireblight". This was short lived, as E. amylovora made its presence known when it was discovered in the later 1990s in Germany. Nonetheless by the 1980s the E. amylovora bacteria had been found in the Eastern Mediterranean, although its appearance in this region is thought to be an isolated appearance and not as a result of local transmission. Finally from the years 1995-1996 cases of fireblight had begun to be reported in countries such as Hungary, Romania, Northern Italy and Northern Spain. ## Symptoms[edit] Fire blight on a pear tree caused by Erwinia amylovora Tissues affected by the symptoms of Erwinia amylovora include blossoms, fruits, shoots, and branches of apple (Pomoideae), pear, and many other rosaceous plants. All symptoms are above ground and are typically easy to recognize. Symptoms on blossoms include water soaking of the floral receptacle, ovary, and peduncles.[5] This results in a dull, gray-green appearance at 1–2 weeks after petal fall, and eventually tissues will shrivel and turn black. The base of the blossom and young fruit show similar symptoms as infection spreads. Opaque white- or amber-colored droplets of bacterial ooze can be seen on the infected tissue when the environment is high in humidity. Shoots show similar symptoms but develop much more rapidly. A “Shepherd's Crook” can be seen when the tip of the shoot wilts, and diseased shoot leaves typically have blackening along the mid-vein and then die. In number, diseased shoots give the tree a blighted appearance. Initial infection of blossoms and shoots can spread to larger tree limbs. Branches will darken and become water soaked. Advanced infection develops cracks in bark and a sunken surface. Wood under the bark will become streaked with black discoloration. Immature fruit forms water-soaked lesions and later turned black. Bacterial ooze can be found on these lesions. Severe infections result in fruit turning entirely black and shriveling.[6] A primary inoculum of this disease is typically from cankers formed the season before. The factors that determine whether or not cankers become active are not well known, but it is thought that cankers found on larger tree limbs are more likely to become active. It is also thought that age may be a factor.[7] ## Dissemination[edit] Gala apple branch with “scorched” leaves after a severe fire blight infection. Honeybees and other insects, birds, rain and wind can transmit the bacterium to susceptible tissue. Injured tissue is also highly susceptible to infection, including punctures and tears caused by plant-sucking or biting insects. Hailstorms can infect an entire orchard in a few minutes, and growers do not wait until symptoms appear, normally beginning control measures within a few hours. Once deposited, the bacterium enters the plant through open stomata and causes blackened, necrotic lesions, which may also produce a viscous exudate. This bacteria-laden exudate can be distributed to other parts of the same plant or to susceptible areas of different plants by rain, birds or insects, causing secondary infections. The disease spreads most quickly during hot, wet weather and is dormant in the winter when temperatures drop. Infected plant tissue contains viable bacteria, however, and will resume production of exudate upon the return of warm weather in the following spring. This exudate is then the source for new rounds of primary infections. The pathogen spreads through the tree from the point of infection via the plant's vascular system, eventually reaching the roots and/or graft junction of the plant. Once the plant's roots are affected, the death of the plant often results. Over pruning and over fertilization (especially with nitrogen) can lead to watersprout and other midsummer growth that leave the tree more susceptible. Erwinia amylovora typically makes its entry into its host xylem or cortical parenchyma. It can also enter through stomata, lenticles and hydathodes. It is dispersed by rain and or insects naturally, but this mode of dispersal is very ineffective and can only be effective for local transmission of the pathogen. Aerosols are also suspected in playing a role in its transmission due to the detection of E. amylovora in Mediterranean regions. In composition the pathogen is composed of short rods with rounded ends made motile by many peritrichous flagellae. E. amylovara is a gram negative bacterium (as stated above). Fire blight microorganisms are spread through different effectively means also, for example, downpour or water sprinkling, bugs, and winged animals, other tainted plants, and unclean cultivating instruments. The most extreme danger of presentation to this bacterium is pre-summer or late-spring as it rises up out of dormancy. Shockingly, there is no solution for fire blight; in this way, the best fire blight cures are standard pruning and expulsion of any tainted stems or branches. It might likewise assist with staying away from the overhead water system, as water sprinkling is one of the most well-known approaches to spread the disease. There should be cautious attention towards the digging tools, particularly those that have been exposed to the microscopic organisms. The tools should be disinfected in an alcohol solution containing three parts denatured alcohol to one part water. Diluted household bleach (one part bleach to nine parts water) can likewise be utilized. Continuously make a point to altogether dry the tools to forestall corrosion. It can also help with assisting to oil them down also.[8] The fly Delia platura has been observed visiting fire blight wounds to feed but was unconfirmed as an effective vector. Eventually it was demonstrated that D. platura does successfully transmit fire blight to already damaged apple shoots.[9] Fire blight exopolysaccharide also served as the adhesive to attach propagated cells to D. platura.[9] D. platura shed fire blight at a constant rate[9] \- and did not suffer from doing so - for at least five days.[9] ## Management[edit] Spraying plants with streptomycin or injecting plants with oxytetracycline can prevent new infections.[10] The widespread use of streptomycin spray has led to antibiotic resistance in some areas, such as California and Washington. Certain biological controls consisting of beneficial bacteria or yeast can also prevent fire blight from infecting new trees. The only effective treatment for plants already infected is to prune off the affected branches and remove them from the area.[11] Plants or trees should be inspected routinely for the appearance of new infections. The rest of the plant can be saved if the blighted wood is removed before the infection spreads to the roots.[12] There is no known cure; prevention is the key.[13] E. amylovora needs to be destroyed externally, before it enters the cell. This is simply because once it enters the host, it spreads during the endophytic phase of pathogenesis. Once this happens external control methods become ineffective. The ideal control method is to apply copper and antibiotics to the plant externally. This is the only effective method and it is indeed preventative. Currently it has been noted that E. amylovora has developed a resistance to the antibiotic streptomycin, as do most bacteria due to their flexible ability to transfer preferential genes promoting resistance to certain antibiotics horizontally from species not even similar to it as all bacteria can.[14] Phytosanitary measures have been employed as the best sanitary measures against E. amylovora dispersal. High risk countries are encouraged not to import plants susceptible to the pathogen into their territory because, once the bacteria become established in an area it is nearly impossible to eradicate the disease. Nurseries and orchards in such regions are placed on strict phytosanitary surveillance measures and well-monitored. Imported and infected crops are destroyed as soon as they are noticed since the bacteria spreads very rapidly and eradication methods are usually costly and inefficient. Current fire blight strategies depend upon phytosanitary measures to lessen inoculum in the plantation and the utilization of splash medicines to forestall contamination, particularly blossom infections. Decreasing essential inoculum in the plantation by removing remainder holdover cankers during winter pruning is a set up as a basic method of control fire blight disease.[15] In seriously influenced plantations, social practices that moderate the development pace of the tree will likewise slow the pace of canker improvement. This incorporates retaining irrigation water, nitrogen fertilizer, and agriculture. Also, practices that decrease tree injuring and bacterial development can diminish auxiliary disease. This incorporates controlling bugs, for example, plant bugs and psylla, constraining utilization of appendage spreaders in youthful plantations, and avoiding use of overhead sprinklers.[16] ## Importance[edit] Besides the historical importance of being the first bacterium proven to be a plant pathogen, it is extremely economically important.[6] Control and loss costs are estimated approximately $100 million a year in the USA. Specifically, in Michigan in the year 2000, $42 million in losses is estimated because of the removal of about 400,000 apple trees.[17] Warm, humid, and wet weather in May resulted in this epidemic. While approximately $68 million is estimated in losses in Washington and northern Oregon. E. amylovora is spread all through the USA and worldwide causing severe damage although it is unlikely to cause severe damage in northern Europe. As long as E. amylovora is not introduced to Central Asia where wild apple trees still grow, it will not modify any ecosystems. Biodiversity is not impacted either, as no plant species are threatened with extinction due to this pathogen. Growing pears in Emilia-Romagna in Italy is a traditional activity for some families, and fire blight threatens this tradition that has been passed down for several generations.[18] In southern Germany apple and pear trees have been a part of the landscape for a long time, and are difficult to protect. The decline of apple and pear trees from their landscape can be expensive to replace and could have a negative effect on tourism. In the long-run, fire blight is a very important factor of economy and society. A predetermined number of apple cultivars are answerable for an enormous extent of yearly creation. Shoppers and general stores prize these cultivars for their appearance, quality, flavor, and storability, while cultivators additionally esteem their plantation attributes and prepared market coming about because of purchaser request. To hold the desirable qualities of a fruiting cultivar while presenting malady opposition qualities through ordinary reproducing techniques is for all intents and purposes unimaginable due to apple's heterozygosity, long age time, and self-incongruence. Hereditary designing offers an appealing option since it can possibly give quicker outcomes, resistance qualities can be acquired from numerous sources, the statement of local apple qualities can be altered, and the attractive characteristics of the changed cultivar or rootstock can be safeguarded.[19] ## Pathogenesis[edit] Pathogenicity depends on many different factors such as the production of the siderophore desferrioxamine, metalloproteases, plasmids, and histone-like proteins. However, some essential factors of pathogenicity are variations in the synthesis of extracellular polysaccharides (EPS) and the mechanism of type III secretion system and its associated proteins.[20] EPS helps bacterial pathogens avoid plant defenses, “clog” the host’s vascular system, protect bacteria against desiccation and attach to both surfaces and one another. One EPS is amylovoran, a polymer of pentasaccharide repeating units. If a strain of E. amylovora can not produce amylovoran it is not pathogenic and can not spread in plants. Levan is another EPS, and a lack of it will slow development of symptoms. Type III secretion systems are used for exporting and delivering effector proteins into the cytosol of host plants. This system mainly consists of Hrc proteins. Motility is another major virulence factor.[21] Since E. amylovora is not an obligate biotroph, it is able to survive outside the host which allows it to spread in many ways such as rain. ## References[edit] 1. ^ Type strain NCPPB 683 Archived 2012-07-11 at WebCite (dead link 3 December 2019) 2. ^ "Australia, New Zealand trade insults over fire blight. (tree disease)". Agra Europe. May 23, 1997. 3. ^ "Local apple producers say no to Kiwis' fruit". Australian Broadcasting Corporation. 2010-04-13. Retrieved November 11, 2014. 4. ^ Helm, Leslie; Eisenstodt, Gale (July 22, 1996). "Caught in Cross-Fire of Pacific Apple War". Los Angeles Times. Retrieved August 9, 2010. 5. ^ Schroth, M.N. (2010). "Fire Blight of Apple and Pear" (PDF). plantdiseases.org. Archived (PDF) from the original on January 18, 2020. Retrieved January 17, 2020. 6. ^ a b Johnson, Kenneth B. "Fire Blight of Apple and Pear." The American Phytopathological Society. The Plant Health Instructor, 2000. Web. 15 Nov. 2016. 7. ^ Beer, Steven V., and Norelli, John L. "Fire Blight Epidemiology: Factors Affecting Release of Erwinia Amylovora by Cankers." Phytopathology 77.9 (1977): 1119-125. Web. 15 Nov. 2016. 8. ^ https://www.gardeningknowhow.com/plant-problems/disease/fire-blight-remedies-and-symptoms.htm 9. ^ a b c d Boucher, Matthew; Collins, Rowan; Harling, Kayli; Brind’Amour, Gabrielle; Cox, Kerik; Loeb, Greg (2020-11-11). "Interactions Between Delia platura and Erwinia amylovora Associated with Insect Mediated Transmission of Shoot Blight". PhytoFrontiers. American Phytopathological Society. 1: PHYTOFR-08-20-0. doi:10.1094/phytofr-08-20-0013-r. ISSN 2690-5442. 10. ^ Iljon A, Stirling J, Smith? RJ (2012). "A mathematical model describing an outbreak of fire blight". In Mushayabasa S, Bhunu, CP (eds.). Understanding the Dynamics of Emerging and Re-Emerging Infectious Diseases Using Mathematical Models. pp. 91–104. ISBN 978-81-7895-549-0. 11. ^ Iljon A, Stirling J, et al. (2012). "A mathematical model describing an outbreak of fire blight". In Mushayabasa S, Bhunu, CP (eds.). Understanding the Dynamics of Emerging and Re-Emerging Infectious Diseases Using Mathematical Models. pp. 91–104. ISBN 978-81-7895-549-0. 12. ^ "Fireblight: Symptoms, Causes and Treatment". University of Georgia. Retrieved November 13, 2014. 13. ^ "Fire Blight". Colorado State University. Retrieved November 13, 2014. 14. ^ "Superbug, super-fast evolution". evolution.berkeley.edu. April 2008. Retrieved 2016-12-12. 15. ^ Norelli, John L.; Jones, Alan L.; Aldwinckle, Herb S. (August 2003). "Fire Blight Management in the Twenty-first Century: Using New Technologies that Enhance Host Resistance in Apple". Plant Disease. 87 (7): 756–765. doi:10.1094/PDIS.2003.87.7.756. ISSN 0191-2917. PMID 30812883. 16. ^ https://www.apsnet.org/edcenter/disandpath/prokaryote/pdlessons/Pages/FireBlight.aspx 17. ^ Aćimović SG, Zeng Q, McGhee GC, Sundin GW and Wise JC (2015) Control of fire blight (Erwinia amylovora) on apple trees with trunk-injected plant resistance inducers and antibiotics and assessment of induction of pathogenesis-related protein genes. Front. Plant Sci. 6:16. Web. 15 Nov. 2016. 18. ^ "Erwinia Amylovora (fireblight)." The Centre for Agriculture and Bioscience International. N.p., n.d. Web. 15 Nov. 2016. 19. ^ Norelli, John L.; Jones, Alan L.; Aldwinckle, Herb S. (2003). "Fire Blight Management in the Twenty-first Century: Using New Technologies that Enhance Host Resistance in Apple". Plant Disease. 87 (7): 756–765. doi:10.1094/PDIS.2003.87.7.756. PMID 30812883. 20. ^ Piqué, Núria, David Miñana-Galbis, Susana Merino, and Juan Tomás. "Virulence Factors of Erwinia Amylovora: A Review." International Journal of Molecular Sciences 16.6 (2015): 12836-2854. Web. 15 Nov. 2016. 21. ^ Vrancken, K., Holtappels, M., et al. (May 2013). Pathogenicity and infection strategies of the fire blight pathogen Erwinia amylovora in Rosaceae: State of the art. Microbiology 159(5):823-832. Web. 15 Nov. 2016 ## External links[edit] Wikimedia Commons has media related to Fire blight. * Type strain of Erwinia amylovora at BacDive \- the Bacterial Diversity Metadatabase * Images of symptoms (973) and database, UC Berkeley Taxon identifiers * Wikidata: Q866091 * Wikispecies: Erwinia amylovora * BacDive: 4386 * EoL: 972704 * EPPO: ERWIAM * GBIF: 3222012 * iNaturalist: 380904 * IRMNG: 10529384 * ISC: 21908 * ITIS: 961539 * LPSN: erwinia.html#amylovora * NCBI: 552 * NZOR: 4c50b5ba-d613-4dfe-af95-28d755e3dd3e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Fire blight	None	27,016	wikipedia	https://en.wikipedia.org/wiki/Fire_blight	2021-01-18T18:54:15	{"wikidata": ["Q41456487"]}
A rare neurologic condition characterized by focal cerebral ischemia and infarction due to blockage of a brain artery with subsequent impairment of blood supply and oxygenation of brain tissue. Most children present with hemiparesis with or without facial palsy at stroke onset. In addition, compared to adults, children more often suffer strokes in the posterior circulation, leading to ataxia or oculomotor disturbance. Likewise, aphasia is more frequent in pediatric patients. Other signs and symptoms include seizures, headache, vomiting, and alterations in the level of consciousness. Children under one year of age are more likely to present with seizures and altered level of consciousness, while older children more often show focal neurological deficits. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Pediatric arterial ischemic stroke	None	27,017	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=439175	2021-01-23T18:05:14	{"icd-10": ["I63.5"], "synonyms": ["Childhood AIS", "Childhood arterial ischemic stroke", "Pediatric AIS"]}
For the "aortopulmonary window" in medical imaging, see Aortopulmonary space. Aortopulmonary window Other namesAortopulmonary septal defect[1] SpecialtyMedical genetics Aortopulmonary window refers to a congenital heart defect similar in some ways to persistent truncus arteriosus.[2] Persistent truncus arteriosus involves a single valve; aortopulmonary window is a septal defect.[3] A large number of patients with a large APW usually die within 1 year of age. It is extremely rare to find cases of APW surviving till adult age and it is still rare to surgically treat such patients who are incidentally detected in adult age because such subsets of patients invariably have associated pulmonary vascular obstructive disease in advanced stage and thus there is therapeutic dilemma to surgically correct these patients.Although cases of uncorrected AP window presenting in adulthood have been reported but literature on surgically treated AP window in adult populations is limited. A rare case of successful surgical management of an incidentally detected large aortopulmonary window with reversible pulmonary arterial hypertension has been reported as isolated case reports. [4] ## See also[edit] * Aortic window * Rare case of a large aortopulmonary window in adult with reversible pulmonary arterial hypertension[4] ## References[edit] 1. ^ "Aortopulmonary window: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 27 May 2019. 2. ^ Stevenson, Roger E.; Hall, Judith G. (2006). Human malformations and related anomalies. Oxford University Press US. pp. 119–. ISBN 978-0-19-516568-5. Retrieved 19 July 2011. 3. ^ Donoghue, Veronica B.; Bjørnstad, Per G. (2007-11-29). Radiological Imaging of the Neonatal Chest. Springer. pp. 330–. ISBN 978-3-540-33748-5. Retrieved 19 July 2011. 4. ^ a b Khanna, Sudhansoo; Mahajan, Sachin; Halder, Vikram; Gowda, Nischitha (2020-04-19). "Incidental diagnosis of a large aortopulmonary window with reversible pulmonary arterial hypertension in adult age and its surgical management". Journal of Cardiac Surgery. doi:10.1111/jocs.14569. ISSN 0886-0440. ## External links[edit] Classification D * ICD-10: Q21.4 * ICD-9-CM: 745.0 External resources * MedlinePlus: 007319 * v * t * e Congenital heart defects Heart septal defect Aortopulmonary septal defect * Double outlet right ventricle * Taussig–Bing syndrome * Transposition of the great vessels * dextro * levo * Persistent truncus arteriosus * Aortopulmonary window Atrial septal defect * Sinus venosus atrial septal defect * Lutembacher's syndrome Ventricular septal defect * Tetralogy of Fallot Atrioventricular septal defect * Ostium primum Consequences * Cardiac shunt * Cyanotic heart disease * Eisenmenger syndrome Valvular heart disease Right * pulmonary valves * stenosis * insufficiency * absence * tricuspid valves * stenosis * atresia * Ebstein's anomaly Left * aortic valves * stenosis * insufficiency * bicuspid * mitral valves * stenosis * regurgitation Other * Underdeveloped heart chambers * right * left * Uhl anomaly * Dextrocardia * Levocardia * Cor triatriatum * Crisscross heart * Brugada syndrome * Coronary artery anomaly * Anomalous aortic origin of a coronary artery * Ventricular inversion This article about a congenital malformation is a stub. You can help Wikipedia by expanding it. * v * t * e This article about a medical condition affecting the circulatory system is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Aortopulmonary window	c0003516	27,018	wikipedia	https://en.wikipedia.org/wiki/Aortopulmonary_window	2021-01-18T19:04:09	{"gard": ["745"], "mesh": ["D001028"], "umls": ["C0003516"], "icd-9": ["745.0"], "icd-10": ["Q21.4"], "wikidata": ["Q616089"]}
Melanoma is a type of skin cancer that begins in pigment-producing cells called melanocytes. This cancer typically occurs in areas that are only occasionally sun-exposed; tumors are most commonly found on the back in men and on the legs in women. Melanoma usually occurs on the skin (cutaneous melanoma), but in about 5 percent of cases it develops in melanocytes in other tissues, including the eyes (uveal melanoma) or mucous membranes that line the body's cavities, such as the moist lining of the mouth (mucosal melanoma). Melanoma can develop at any age, but it most frequently occurs in people in their fifties to seventies and is becoming more common in teenagers and young adults. Melanoma may develop from an existing mole or other normal skin growth that becomes cancerous (malignant); however, many melanomas are new growths. Melanomas often have ragged edges and an irregular shape. They can range from a few millimeters to several centimeters across. They can also be a variety of colors: brown, black, red, pink, blue, or white. Most melanomas affect only the outermost layer of skin (the epidermis). If a melanoma becomes thicker and involves multiple layers of skin, it can spread to other parts of the body (metastasize). A large number of moles or other pigmented skin growths on the body, generally more than 25, is associated with an increased risk of developing melanoma. Melanoma is also a common feature of genetic syndromes affecting the skin such as xeroderma pigmentosum. Additionally, individuals who have previously had melanoma are nearly nine times more likely than the general population to develop melanoma again. It is estimated that about 90 percent of individuals with melanoma survive at least 5 years after being diagnosed. ## Frequency In the United States, melanoma is the fifth most common cancer in men, affecting 30 in 100,000 men per year, and the sixth most common cancer in women, affecting 18 in 100,000 women per year. About 1 in 43 individuals in the United States will develop melanoma in their lifetime. Light-skinned people have a 20 times greater risk of developing melanoma than dark-skinned people. ## Causes Melanoma is caused by a combination of environmental and genetic factors. The greatest environmental risk factor for developing melanoma is exposure to ultraviolet (UV) radiation from the sun. The risk for melanoma is greatest in individuals who have brief but intense sun exposure rather than moderate, long-term exposure. UV radiation can also come from tanning beds (indoor tanning). UV radiation damages DNA. Most of the time, this kind of DNA damage causes cells to self-destruct (undergo apoptosis) or permanently stop cell division (undergo senescence). However, melanocytes are more resistant than other kinds of cells to the effects of UV radiation. Even if their DNA is damaged, melanocytes are unlikely to undergo apoptosis. As abnormal melanocytes continue to grow, they accumulate genetic mutations, particularly in genes that control cell growth and division (proliferation), senescence, and apoptosis. Ultimately, the cells become able to proliferate without control or limit and can resist cell death, leading to the formation and growth of a melanoma. Most cases of melanoma are sporadic, which means that the genetic changes are acquired during a person's lifetime and are present only in the melanocytes that give rise to the melanoma. These changes, which are called somatic mutations, are not inherited. Studies suggest that in some cases somatic variations in multiple genes, each with a small effect, combine to increase the risk of developing the condition. Many of these gene variations are associated with a light complexion and increased freckling and moles. However, it is unclear what contribution each of these genetic changes makes to disease risk. Other somatic gene mutations have large effects on melanoma risk and a mutation in one gene is enough to significantly increase the risk of developing cancer. Somatic mutations in the BRAF and CDKN2A genes are some of the most common in sporadic melanoma. In about 10 percent of cases, melanoma occurs in multiple members of the same family. Unlike sporadic melanoma, these familial cases are typically caused by inherited genetic changes that increase the risk of developing this type of cancer. These genetic changes, which are classified as germline mutations, are present in essentially all of the body's cells. The primary genes involved in familial melanoma are CDKN2A and MC1R. The CDKN2A gene plays a role in regulating cell senescence and the MC1R gene influences skin pigmentation. Shared nongenetic factors can also influence the development of melanoma in family members; for example, family members may live in the same sun-exposed environment. In people with germline mutations, changes in other genes, together with environmental and lifestyle factors, also contribute to the possible development of melanoma. ### Learn more about the genes associated with Melanoma * ATM * BAP1 * BRAF * CDKN2A * MC1R * MITF * NRAS * OCA2 * PLA2G6 * SLC45A2 * TERT * TP53 * TYR * TYRP1 Additional Information from NCBI Gene: * ASIP * CASP8 * CDK10 * CDK4 * EGF * HERC2 * IRF4 * KITLG * MTAP * MX2 * MYH7B * PIGU * POT1 * SLC2A4 * TPCN2 * XRCC3 ## Inheritance Pattern Most cases of melanoma are sporadic, which means that they occur in people with no apparent history of the disorder in their family. When the disorder is familial, it can be due to shared environmental factors or shared genetic factors or both. The genetic factors are usually inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase the risk of developing melanoma. When melanoma occurs as part of a genetic syndrome, the risk of melanoma follows the inheritance pattern of the 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Melanoma	c2314896	27,019	medlineplus	https://medlineplus.gov/genetics/condition/melanoma/	2021-01-27T08:25:05	{"gard": ["3460", "91"], "omim": ["155600", "615848", "155601", "609048", "608035", "613099", "613972", "612263", "614456", "615134"], "synonyms": []}
Congenital Epstein-Barr virus (EBV) infection causes no clinical manifestations in the majority of infants. Indeed, the occurrence of congenital infection with EBV has never been demonstrated conclusively and must be very rare. One case have been reported to present after birth, multiple congenital anomalies (micrognathia, cryptorchidism, central cataracts), dystrophy, generalized hypotonia, hepatosplenomegaly, diffuse petechiae and hematomas and multiple areas of metaphysitis of the long bones at birth. A low birth weight was also reported. No specific follow-up of the fetus is recommended following maternal EBV primary-infection. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Congenital Epstein-Barr virus infection	c4274357	27,020	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=70596	2021-01-23T17:29:43	{"icd-10": ["P35.8"], "synonyms": ["Antenatal EBV infection", "Antenatal Epstein-Barr virus infection", "Congenital EBV infection", "Mother-to-child transmission of Epstein-Barr virus infection"]}
## Summary ### Clinical characteristics. Aicardi syndrome is a neurodevelopmental disorder that affects primarily females. Initially it was characterized by a typical triad of agenesis of the corpus callosum, central chorioretinal lacunae, and infantile spasms. As more affected individuals have been ascertained, it has become clear that not all affected girls have all three features of the classic triad and that other neurologic and systemic defects are common, including other brain malformations, optic nerve abnormalities, other seizure types, intellectual disability of varying severity, and scoliosis. ### Diagnosis/testing. The diagnosis of Aicardi syndrome is based exclusively on clinical findings. Modified diagnostic criteria include either presence of the classic triad or the presence of two of the classic triad plus at least two other major or supporting features. A gene for Aicardi syndrome has not been identified, but several observations support a hypothesis that Aicardi syndrome is caused by de novo pathogenic variants in a gene on the X chromosome that is subject to X-chromosome inactivation. ### Management. Treatment of manifestations: Treatment is individualized and long-term management by a pediatric neurologist with expertise in management of infantile spasms and medically refractory epilepsy is essential. Physical therapy, occupational therapy, and speech therapy should begin at the time of diagnosis. Appropriate musculoskeletal support and treatment for prevention of scoliosis-related complications is indicated. Surveillance: Includes routine monitoring of growth, nutritional status and safety of oral intake, seizure control, developmental progress and educational needs, respiratory function and aspiration risk, and the spine and degree of scoliosis. ### Genetic counseling. With the exception of affected monozygotic twin girls, all individuals with Aicardi syndrome reported to date have represented simplex cases (i.e., a single affected family member). Parent-to-child transmission of Aicardi syndrome has not been reported, and the recurrence risk to sibs is thought to be less than 1%. While prenatal ultrasound or intrauterine MRI findings of corpus callosum agenesis and neuronal migration abnormalities may be suggestive of Aicardi syndrome, no findings are diagnostic. ## Diagnosis No consensus clinical diagnostic criteria for Aicardi syndrome have been published. The diagnosis of Aicardi syndrome is based exclusively on clinical findings. Modified diagnostic criteria have been proposed [Sutton et al 2005, adapted from Aicardi 1999]: * The presence of the classic triad is diagnostic for Aicardi syndrome. * The presence of two of the classic triad plus at least two other major or supporting features is strongly suggestive of the diagnosis of Aicardi syndrome. Classic triad * Agenesis of the corpus callosum * Distinctive chorioretinal lacunae * Infantile spasms Major features * Cortical malformations (mostly polymicrogyria) * Periventricular and subcortical heterotopia * Cysts around third cerebral ventricle and/or choroid plexus * Optic disc/nerve coloboma or hypoplasia Supporting features * Vertebral and rib abnormalities * Microphthalmia * "Split-brain" EEG * Gross cerebral hemispheric asymmetry * Vascular malformations or vascular malignancy Note: Aicardi syndrome appears to be an X-linked dominant disorder with lethality in males; however, no gene or candidate region on the X chromosome has been identified (see Molecular Pathogenesis). ## Clinical Characteristics ### Clinical Description Aicardi syndrome, first described by Aicardi et al [1965], is a neurodevelopmental disorder that affects primarily females [Aicardi 1999, Van den Veyver 2002, Aicardi 2005]. Initially it was characterized by a typical triad of agenesis of the corpus callosum, typical chorioretinal lacunae, and infantile spasms; however, as more affected individuals have been ascertained, it has become clear that other neurologic and systemic defects are common. Indeed, not all affected girls have all three features of the classic triad (see Table 1). ### Table 1. Select Features of Aicardi Syndrome View in own window Feature% of Persons w/FeatureComment NeurologicSeizures>95%Nearly all present w/infantile spasms in 1st mos of life; various other seizure types develop over time. ID/DD100%Many have severe-profound ID & do not develop language or ability to walk or sit independently; however, the degree of developmental impairment varies. Structural brain malformations100%While agenesis of the corpus callosum is part of the classic triad, virtually all have other brain malformations (e.g., heterotopias, cysts). OcularChorioretinal lacunae100%Typically in central part of retina (not periphery); may cause visual impairment if they involve the macula; may be bilateral or unilateral Optic nerve abnormalities>90%Colobomas & hypoplasia of optic nerves are common & → visual impairment. OtherCostovertebral abnormalities~50%Fusion of vertebrae & ribs can be seen, often (along w/severe hypotonia) → scoliosis. Based on Wong & Sutton [2018] DD = developmental delay; ID = intellectual disability Neurologic. The neurologic examination can reveal microcephaly, axial hypotonia, and appendicular hypertonia with spasticity often affecting one side and brisk deep tendon reflexes as well as hemiparesis [Aicardi 2005; Author, unpublished data]. Moderate-to-severe developmental delay and intellectual disability are typical, although individuals with only mild or no learning disabilities or developmental delay have been reported (reviewed in Wong & Sutton [2018]). Many girls with Aicardi syndrome develop seizures before age three months, and most before age one year. Infantile spasms are seen early on; ongoing medically refractory epilepsy with a variety of seizure types develops over time. Common EEG findings include asynchronous multifocal epileptiform abnormalities with burst suppression and dissociation between the two hemispheres. Brain MRI reveals dysgenesis of the corpus callosum, which is most often complete but can be partial. Polymicrogyria or pachygyria, which are predominantly frontal and perisylvian and associated with underopercularization, are typical. Periventricular and intracortical gray matter heterotopia are very common. Gross cerebral asymmetry, choroid plexus papillomas, ventriculomegaly, and intracerebral cysts, often at the third ventricle and in the choroid plexus, are frequently present [Aicardi 2005, Hopkins et al 2008]. Recently, posterior fossa and cerebellar abnormalities are increasingly recognized as important components of the phenotype [Hopkins et al 2008, Steffensen et al 2009]. Ophthalmologic. The pathognomonic chorioretinal lacunae of Aicardi syndrome are white or yellow-white, well-circumscribed, round, depigmented areas of the retinal pigment epithelium and underlying choroid with variably dense pigmentation at their borders (Figure 1) [Fruhman et al 2012] that can cluster in the posterior pole of the globe around the optic nerve. The sensory retina overlying the lacunae is usually intact but may be disorganized or entirely absent. #### Figure 1. Classic lacunae surround the modestly dysplastic left optic disc. Note the nasal "papilla nigra" appearance and the anomalous branching patterns of the central vasculature. Image courtesy of Dr Richard A Lewis Almost all individuals have some ocular abnormalities. Fruhman et al [2012] described data on 40 females with Aicardi syndrome examined by a single expert ophthalmologist and retinal specialist. Of the 75 eyes that could be evaluated, all had chorioretinal lacunae. Other common optic nerve findings included: * Coloboma (39% of eyes) * Glial proliferation (19% of eyes) * Severe dysplasia (17% of eyes) * Pseudoadenomatous proliferation of the retinal pigment epithelium (14% of eyes) All eye findings can be unilateral or bilateral and asymmetric. Craniofacial. Characteristic facial features reported in Aicardi syndrome include a short philtrum, prominent premaxilla with resultant upturned nasal tip and decreased angle of the nasal bridge, large ears, and sparse lateral eyebrows [Sutton et al 2005]. Plagiocephaly and facial asymmetry, occasionally with cleft lip and palate (3%), have been reported. Pierre-Robin sequence has been reported in a single case [Jensen & Christiansen 2004]. Skeletal. Costovertebral defects, such as hemivertebrae, block vertebrae, fused vertebrae, and missing ribs, are common and can lead to marked scoliosis in up to one third of affected individuals [Donnenfeld et al 1989]. Hip dysplasia has been reported. Gastrointestinal. Constipation, gastroesophageal reflux, diarrhea, and feeding difficulties are perceived by parents to be the second most difficult problem to manage (after seizures) [Glasmacher et al 2007]. Extremities. Small hands, along with an increased incidence of hand malformations, have been reported [Sutton et al 2005]. Dermatologic. An increased incidence of vascular malformations and pigmentary lesions has been observed [Sutton et al 2005]. Tumors/malignancies. The incidence of tumors may be increased. A variety of rare tumor types have been reported: benign tumors such as choroid plexus papillomas [Taggard & Menezes 2000, Pianetti Filho et al 2002] and lipomas, as well as malignant tumors including angiosarcomas, hepatoblastomas, meduloblastoma, embryonal carcinomas, and teratomas [Sutton et al 2005, Wharton et al 2018]. Growth. The average heights and weights of girls with Aicardi syndrome closely follow those of the general population up to ages seven and nine years, respectively, after which the growth rate for both height and weight is lower. Growth curves for Aicardi syndrome based on parent survey data have been published [Glasmacher et al 2007]. The weight-versus-height ratio remains similar to the general population. Endocrine. Either precocious puberty or delayed puberty may be present [Glasmacher et al 2007]. Survival. Survival in Aicardi syndrome is highly variable and likely depends on the severity of seizures. In a survey by Glasmacher et al [2007], the mean age at death was 8.3 years, although the median age of death was 18.5 years. The ages of death were distributed from before age one year to older than 23 years. The oldest surviving individual reported in this survey was age 32 years. Another paper also indicated that the survival is longer than previously reported, especially in more mildly affected individuals, with the highest risk of death at age 16 years and a probability of survival at age 27 years of 0.62 [Kroner et al 2008]. ### Nomenclature Note: Aicardi syndrome is NOT related to Aicardi-Goutières syndrome, an early-onset encephalopathy. ### Prevalence Aicardi syndrome is very rare and appears to affect all ethnicities equally. Its incidence has been estimated at between 1:105,000 and 1:167,000 in the United States and between 1:93,000 and 1:99,000 in some European countries [Kroner et al 2008]. The exact prevalence of Aicardi syndrome is unknown; it has been estimated to be at least 853 in the US and over 4,000 worldwide [Kroner et al 2008]. ## Differential Diagnosis Agenesis of the corpus callosum may occur in isolation, in conjunction with other brain malformations, or as part of a larger syndrome. It has been suggested that agenesis of the corpus callosum in association with cysts that do not communicate with the ventricles and presence of subependymal heterotopia and polymicrogyria is relatively specific for Aicardi syndrome [Barkovich et al 2001]. Neuronal migration disorders, including polymicrogyria (see also Polymicrogyria Overview), pachygyria, and heterotopia, may occur as isolated malformations or as part of the phenotype associated with other syndromes or chromosome abnormalities. Infantile spasms are observed in most girls with Aicardi syndrome, but this type of seizure is not specific for Aicardi syndrome. Infantile spasms may occur in isolation or as part of the phenotype of other syndromes, inborn errors of metabolism, or chromosome disorders. Hereditary disorders. See Table 2. ### Table 2. Genes of Interest in the Differential Diagnosis of Aicardi Syndrome View in own window Gene(s)DiffDx DisorderMOIFeatures of DiffDx Disorder NeurologicOphthalmologicOtherDistinguishing from AIC COX7B HCCS NDUFB11Microphthalmia w/linear skin defects syndromeXLCorpus callosum agenesis, seizures, IDMicrophthalmia, cataract, colobomaLinear skin defectsCharacteristic linear skin defects FLNAX-linked periventricular heterotopiaXLNeuronal migration defects, seizures, IDNone–No ophthalmic abnormalities KIF11MCLMR (OMIM 152950)ADSevere microcephaly, IDPeripheral retinal defectsLymphedemaMicrocephaly is severe, neuronal migration defects uncommon, chorioretinal changes peripheral, & optic nerves normal. 1 PLK4MCCRP2 (OMIM 616171)ARSevere microcephaly, IDCataract, microcorneaShort statureMicrocephaly is severe. PORCNFocal dermal hypoplasia (Goltz syndrome)XLNormal & IDMicrophthalmia, colobomaCutis aplasia, telangectasias & other dermatologic abnormalitiesCharacteristic skin defects TSC1 TSC2Tuberous sclerosis complexADInfantile spasms, cortical tubersAchromic retinal patchesRenal cystsAbsence of characteristic eye findings of Aicardi syndrome TUBGCP4MCCRP3 (OMIM 616335)ARSevere microcephaly, IDPeripheral retinal defects, microphthalmia–Microcephaly is severe, chorioretinal changes peripheral, & optic nerves normal. 1 TUBGCP6MCCRP1 (OMIM 251270)ARSevere microcephaly, IDPeripheral retinal defects, microphthalmiaShort statureMicrocephaly is severe, chorioretinal changes peripheral, & optic nerves normal. 1 AD = autosomal dominant; AIC = Aicardi syndrome; AR = autosomal recessive; DiffDx = differential diagnosis; ID = intellectual disability; MCCRP = microcephaly and chorioretinopathy, autosomal recessive; MCLMR = microcephaly with or without chorioretinopathy, lymphedema, or mental retardation; MOI = mode of inheritance; XL = X-linked 1\. In contrast to AIC, in which chorioretinal lacunae are central & optic nerves almost always involved Syndromes of unknown cause * Orofaciodigital syndrome type IX (OFD9; OMIM 258865). Although chorioretinal lacunae are virtually pathognomonic for Aicardi syndrome, they have also been reported in OFD . * Oculocerebrocutaneous syndrome (OMIM 164180) characterized by orbital cysts and anophthalmia or microphthalmia, focal skin defects, brain malformations that include polymicrogyria, periventricular nodular heterotopias, enlarged lateral ventricles, and agenesis of the corpus callosum, is predominant in males and has a pathognomonic mid-hindbrain malformation [Moog et al 2005]. ## Management No clinical practice guidelines for Aicardi syndrome have been published. ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with Aicardi syndrome, 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 Aicardi Syndrome View in own window System/ConcernEvaluationComment ConstitutionalMeasure height, weight, head circumference. NeurologicNeurologic eval * To incl brain MRI * Consider EEG if seizures are a concern. DevelopmentDevelopmental assessment * To incl motor, adaptive, cognitive, & speech/language eval * Eval for early intervention / special education Psychiatric/ BehavioralNeuropsychiatric evalFor persons age >12 mos: screening for behavior concerns incl sleep disturbances, ADHD, anxiety, &/or traits suggestive of ASD Costovertebral abnormalitiesSpine radiographs * To evaluate for hemivertebrae, block vertebrae, fused vertebrae; missing, malformed, fused ribs * Orthopedics consultation if costovertebral abnormalities are significant Musculoskeletal / Activities of daily livingPhysical medicine & rehabilitation / PT / OT evalTo incl assessment of: * Gross motor & fine motor skills * Mobility, activities of daily living, & need for adaptive devices * Need for PT (to improve gross motor skills) &/or OT (to improve fine motor skills) Gastrointestinal/ FeedingGastroenterology/nutrition/ feeding team evalTo incl: * History of constipation, diarrhea, GERD * Eval of aspiration risk & nutritional status Consider eval for gastric tube placement in patients w/dysphagia &/or aspiration risk. Eyes/VisionOphthalmologic evalTo assess for ↓ vision, abnormal ocular movement, strabismus EndocrinePhysical exam for evidence of precocious or delayed puberty SkinDermatologic evalFor vascular malformations & pigmentary lesions at risk for malignant transformation Risk of malignancyNo regular screening recommended, given variety of tumors seen. Treating clinicians should be alert to risk of malignancy.Angiosarcoma, hepatoblastoma, medulloblastoma, embryonal carcinoma, & teratoma have been reported. Genetic counselingBy genetics professionals 1To date, no gene has been identified as causative of Aicardi syndrome. Genetic testing may be warranted to rule out aforementioned differential diagnoses, esp if presentation is not classic for Aicardi syndrome. Family support/ resourcesAssess: * Use of community or online resources such as Parent to Parent; * Need for social work involvement for parental support; * Need for home nursing referral. ADHD = attention-deficit/hyperactivity disorder; ASD = autism spectrum disorder; GERD = gastroesophageal reflux disease; MOI= mode of inheritance; OT = occupational therapy; PT = physical therapy 1\. Medical geneticist, certified genetic counselor, certified advanced genetic nurse ### Treatment of Manifestations ### Table 4. Treatment of Manifestations in Individuals with Aicardi Syndrome View in own window Manifestation/ConcernTreatmentConsiderations/Other Developmental delay / Intellectual disabilitySee Developmental Delay / Intellectual Disability Management Issues. EpilepsyStandardized treatment w/AEDs by experienced neurologist; recent studies have shown up to 50% ↓ in median number of seizures w/cannabidiol. 1 * Most persons require multiple medications for mgmt of seizures, & seizure types may change over time, requiring changes in medications. * Education of parents/caregivers 2 Poor weight gain / Failure to thriveFeeding therapy; gastrostomy tube placement may be required for persistent feeding issues.Low threshold for clinical feeding eval &/or radiographic swallowing study if clinical signs or symptoms of dysphagia Mobility / Activities of daily livingOrthopedics / physical medicine & rehabilitation / PT / OT incl stretching to help avoid contractures & fallsConsider need for positioning & mobility devices, hygiene, disability parking placard. Abnormal vision &/or strabismusStandard treatment(s) as recommended by ophthalmologistCommunity vision services through early intervention or school district Costovertebral abnormalitiesPer treating orthopedistCan incl musculoskeletal support & treatment for prevention of scoliosis-related complications Bowel dysfunctionMonitor for constipation.Stool softeners, prokinetics, osmotic agents, or laxatives as needed AED = antiepileptic drug; OT = occupational therapy; PT = physical therapy 1\. Devinsky et al [2018] 2\. Education of parents/caregivers regarding common seizure presentations is appropriate. For information on non-medical interventions and coping strategies for children diagnosed with epilepsy, see Epilepsy & My Child Toolkit. #### Developmental Delay / Intellectual Disability Management Issues The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country. Ages 0-3 years. Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy as well as infant mental health services, special educators, and sensory impairment specialists. In the US, early intervention is a federally funded program available in all states that provides in-home services to target individual therapy needs. Ages 3-5 years. In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed for those who qualify based on established motor, language, social, or cognitive delay. The early intervention program typically assists with this transition. Developmental preschool is center based; for children too medically unstable to attend, home-based services are provided. All ages. Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life. Some issues to consider: * Individualized education plan (IEP) services: * An IEP provides specially designed instruction and related services to children who qualify. * IEP services will be reviewed annually to determine whether any changes are needed. * As required by special education law, children should be in the least restrictive environment feasible at school and included in general education as much as possible and when appropriate. * Vision and hearing consultants should be a part of the child's IEP team to support access to academic material. * PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child's access to academic material. Beyond that, private supportive therapies based on the affected individual's needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician. * As a child enters the teen years, a transition plan should be discussed and incorporated in the IEP. For those receiving IEP services, the public school district is required to provide services until age 21. * A 504 plan (Section 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text. * Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a US public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities. * Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability. #### Communication Issues Consider evaluation for alternative means of communication (e.g., Augmentative and Alternative Communication [AAC]) for individuals who have expressive language difficulties. An AAC evaluation can be completed by a speech-language pathologist who has expertise in the area. The evaluation will consider cognitive abilities and sensory impairments to determine the most appropriate form of communication. AAC devices can range from low-tech, such as picture exchange communication, to high-tech, such as voice-generating devices. Contrary to popular belief, AAC devices do not hinder verbal development of speech and in many cases, can improve it. #### Social/Behavioral Concerns 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 typically performed one on one with a board-certified behavior analyst. Consultation with a developmental pediatrician may be helpful in guiding parents through appropriate behavior management strategies or providing prescription medications, such as medication used to treat attention-deficit/hyperactivity disorder (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 Aicardi Syndrome View in own window System/ConcernEvaluationFrequency Feeding * Measure growth parameters. * Evaluate nutritional status & safety of oral intake. At each visit GastrointestinalMonitor for constipation & other bowel problems; stool softeners or pro-motility agents as needed. RespiratoryMonitor for evidence of aspiration, respiratory insufficiency. Neurologic * Monitor those w/seizures as clinically indicated. * Assess for new manifestations incl seizures, changes in tone (e.g., spasticity), movement disorders. DevelopmentMonitor developmental progress & educational needs. Psychiatric/ BehavioralBehavioral assessment for anxiety, attention, & aggressive or self-injurious behavior MusculoskeletalPhysical medicine, OT/PT assessment of mobility, self-help skills Costovertebral abnormalitiesMonitor spine for progression of scoliosis (by exam; perform radiographs as needed). Precocious or delayed pubertyPediatric endocrinologist w/hormonal testing & supplementation as neededIf symptomatic MalignancyTreating physicians should be aware of possible ↑ risk of rare malignancies; if there are symptoms concerning for a malignancy, consider screening. Family / Care giversAssess family need for social work support (e.g., palliative/respite care, home nursing, other local resources) & care coordination.At each visit OT = occupational therapy; PT = physical therapy ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to genetic counseling of relatives at risk. ### 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Aicardi Syndrome	c0175713	27,021	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1381/	2021-01-18T20:47:00	{"mesh": ["D058540"], "synonyms": []}
CLN5 disease is an inherited disorder that primarily affects the nervous system. The signs and symptoms of this condition can begin anytime between childhood and early adulthood, but they typically appear around age 5. Children with CLN5 disease often have normal development until they experience the first signs of the condition, which are usually problems with movement and a loss of previously acquired motor skills (developmental regression). Other features of the condition include recurrent seizures that involve uncontrollable muscle jerks (myoclonic epilepsy), difficulty coordinating movements (ataxia), vision loss, and a decline in intellectual function. The life expectancy of people with CLN5 disease varies; affected individuals usually survive into adolescence or mid-adulthood. CLN5 disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs), which may also be collectively referred to as Batten disease. All these disorders affect the nervous system and typically cause worsening problems with vision, movement, and thinking ability. The different NCLs are distinguished by their genetic cause. Each disease type is given the designation "CLN," meaning ceroid lipofuscinosis, neuronal, and then a number to indicate its subtype. ## Frequency The incidence of CLN5 disease is unknown; more than 85 cases have been described in the scientific literature. CLN5 disease was originally thought to affect only the Finnish population as they were the first individuals to be diagnosed with the condition. However, research has since shown that CLN5 disease affects populations worldwide. NCLs, including CLN5 disease, are still most common in Finland, where approximately 1 in 12,500 individuals are affected. Collectively, all forms of NCL affect an estimated 1 in 100,000 individuals worldwide. ## Causes CLN5 disease is caused by mutations in the CLN5 gene, which provides instructions for making a protein whose function is not well understood. After the CLN5 protein is produced, it is transported to cell compartments called lysosomes, which digest and recycle different types of molecules. Research suggests that the CLN5 protein may play a role in the process by which lysosomes break down or recycle damaged or unneeded proteins within the cell. Most of the CLN5 gene mutations alter the structure of the protein so that it cannot get to the lysosomes where it is needed. A lack of functional protein within lysosomes probably impairs the breakdown of certain proteins, which then likely accumulate in cells throughout the body. While these accumulations can damage any cells, nerve cells appear to be particularly vulnerable. Widespread loss of nerve cells in CLN5 disease leads to severe signs and symptoms and early death. In the cases in which CLN5 disease develops in adolescence or adulthood, it is thought that the CLN5 gene mutations lead to a CLN5 protein with reduced function that is broken down earlier than normal. Because the altered CLN5 protein can function for a small amount of time, some damaged or unneeded proteins may be broken down in lysosomes. Since it takes longer for these substances to accumulate and cause nerve cell death, the signs and symptoms of CLN5 disease in these individuals occur later in life. ### Learn more about the gene associated with CLN5 disease * CLN5 ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	CLN5 disease	c1850442	27,022	medlineplus	https://medlineplus.gov/genetics/condition/cln5-disease/	2021-01-27T08:25:29	{"gard": ["1223"], "mesh": ["C575534"], "omim": ["256731"], "synonyms": []}
A number sign (#) is used with this entry because of evidence that autosomal dominant Robinow syndrome-2 (DRS2) is caused by heterozygous mutation in the DVL1 gene (601365) on chromosome 1p36. Description Robinow syndrome is a skeletal dysplasia characterized by distinctive facial features, including midface hypoplasia, hypertelorism, a short nose, and a broad mouth, known collectively as 'fetal facies.' Additional features include mesomelic dwarfism, macrocephaly, gingival hypertrophy, dental malocclusion, genital hypoplasia, and brachydactyly (summary by Bunn et al., 2015). Additionally, increased skull bone density and appendicular osteosclerosis are present in patients with DRS2 (White et al., 2015; Bunn et al., 2015). For a discussion of genetic heterogeneity of Robinow syndrome, see RRS (268310). Clinical Features Saraiva et al. (1999) reported a pair of monozygotic twin brothers of Portuguese descent with Robinow syndrome. Both had distinctive facial features, including frontal bossing with a larger anterior fontanel, prominent eyes, hypertelorism, small upturned nose, triangular mouth, and gingival hyperplasia. Skeletal anomalies included mesomelic upper limb shortening and short fingers and toes. Each boy also had a small penis and cryptorchidism. At age 14 years, growth and development were normal, and the facial features had become less striking. Saraiva et al. (1999) postulated autosomal dominant inheritance. Eijkenboom et al. (2012) reported a 17-year-old girl with Robinow syndrome and low-frequency conductive hearing impairment. During childhood she had experienced chronic otitis media with effusion. A perforation of the left tympanic membrane was present. CT scan showed thickening and generalized sclerosis of the calvarium. Exploratory tympanotomy confirmed narrowing of the middle ear cavity, oval and round window niches due to the bony overgrowth, and a thickening and fixation of partially dysmorphic ossicles. Bunn et al. (2014) reported 2 unrelated patients with Robinow syndrome. A 21-year-old woman had presented at birth with characteristic facial features, brachydactyly, camptodactyly, and clinodactyly. She had chronic otitis media resulting in conductive and sensorineural hearing loss. She also had oligodontia. At age 13 years, she had downslanting palpebral fissures with hypertelorism, midface hypoplasia, wide and depressed nasal bridge, short nose with narrow nares, and gingival hypertrophy. The second patient was a 9-year-old boy born of Latin American parents. At birth he had cleft lip and palate, umbilical hernia, and cryptorchidism. In childhood he was noted to have dysmorphic facial features, including hypertelorism, broad nasal root, flattened nasal tip, narrow nares, gingival hyperplasia, and dental crowding. Radiographs of both patients showed generalized osteosclerosis affecting the skull and axial and appendicular skeleton, undertubulation of the long bones with cortical thickening, and hypoplastic distal phalanges. Serum alkaline phosphatase was increased in 1 patient. Both patients had normal cognitive function. White et al. (2015) reported 6 unrelated patients with DRS2, as well as the twins originally reported by Saraiva et al. (1999). All had macrocephaly, frontal bossing, high forehead, midface hypoplasia, hypertelorism, short nose, and dental anomalies. Additional common features included prominent eyes, anteverted nares, long philtrum, triangular mouth, thin upper lip, gingival hyperplasia, micrognathia, and abnormal ear shape or position. Skeletal features included mesomelia, brachydactyly, clinodactyly, broad first toes and thumbs, hypoplastic phalanges, and pectus anomalies. Only 2 patients had short stature. Urogenital features such as micropenis and cryptorchidism were present in some patients. Molecular Genetics In 8 patients, including a pair of monozygotic twins reported by Saraiva et al. (1999), with autosomal dominant Robinow syndrome-2, White et al. (2015) identified 6 different de novo heterozygous truncating mutations in the DVL1 gene (see, e.g., 601365.0001-601365.0004). Mutations in the first 3 patients were found by whole-exome sequencing; subsequent patients were identified from a cohort of 62 additional individuals with a similar phenotype who underwent targeted sequencing of the DVL1 gene. Functional studies of the variants were not performed, but studies of 2 patients' cells showed that the truncated proteins were expressed. In 3 unrelated patients with DRS2 (Eijkenboom et al., 2012 and Bunn et al., 2014), Bunn et al. (2015) identified 3 different heterozygous mutations in the DVL1 gene (601365.0004-610365.0006), all of which resulted in premature termination of the protein and addition of an abnormal, highly basic C-terminal sequence. Analysis of cells from 1 of the patients showed that the mutation (c.1519del; 601365.0004) was translated into a stable protein and not degraded by nonsense-mediated mRNA decay. In vitro cellular expression studies showed that cotransfection of the mutation with wildtype DVL1 resulted in increased canonical WNT (see 164820) activity. In 17 Robinow syndrome cases from an in-house database, White et al. (2016) performed Sanger sequencing of the penultimate and final exons of the DVL1, DVL2 (602151), and DVL3 (601368) genes and identified heterozygosity for a de novo 1-bp deletion in DVL1 in a Turkish patient. In addition, 4 mutations were detected in the DVL3 gene in 4 probands (see DRS3, 616894). White et al. (2016) stated that the phenotypic features of DVL1- and DVL3-mediated Robinow syndrome were largely concordant, but noted that only 2 of the 4 DVL3-mutated patients for whom clinical information was available had macrocephaly and all 4 had short stature, suggesting that head circumference and stature might be distinguishing features. INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature (in some patients) HEAD & NECK Head \- Macrocephaly Face \- Frontal bossing \- High forehead \- Midface hypoplasia \- Long philtrum \- Micrognathia (in some patients) Ears \- Conductive hearing loss (in some patients) \- Sensorineural hearing loss (in some patients) \- Abnormal ear shape (in some patients) \- Abnormal ear position (in some patients) Eyes \- Hypertelorism \- Prominent eyes Nose \- Short nose \- Wide, low nasal bridge \- Anteverted nares Mouth \- Triangular mouth \- Thin upper lip \- Gingival hyperplasia Teeth \- Dental anomalies \- Malocclusion \- Dental crowding CHEST Ribs Sternum Clavicles & Scapulae \- Pectus anomalies ABDOMEN External Features \- Umbilical hernia (in some patients) GENITOURINARY External Genitalia (Male) \- Micropenis Internal Genitalia (Male) \- Cryptorchidism SKELETAL \- Osteosclerosis (in some patients) Skull \- Thickened calvaria (in some patients) Limbs \- Mesomelia (in some patients) \- Undertubulated long bones (in some patients) Hands \- Brachydactyly \- Clinodactyly \- Broad thumbs \- Hypoplastic distal phalanges Feet \- Brachydactyly \- Broad first toes \- Hypoplastic distal phalanges MISCELLANEOUS \- Onset at birth MOLECULAR BASIS \- Caused by mutation in the dishevelled segment polarity protein 1 gene (DVL1, 601365.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	ROBINOW SYNDROME, AUTOSOMAL DOMINANT 2	c0265205	27,023	omim	https://www.omim.org/entry/616331	2019-09-22T15:49:11	{"doid": ["0060765"], "mesh": ["C562492"], "omim": ["616331"], "orphanet": ["3107", "97360"], "genereviews": ["NBK268648"]}
## Summary ### Clinical characteristics. Ataxia with oculomotor apraxia type 2 (AOA2) is characterized by onset of ataxia between age three and 30 years after initial normal development, axonal sensorimotor neuropathy, oculomotor apraxia, cerebellar atrophy, and elevated serum concentration of alpha-fetoprotein (AFP). ### Diagnosis/testing. The diagnosis of AOA2 is based on clinical, laboratory, and radiographic features; family history; and exclusion of the diagnosis of ataxia-telangiectasia, AOA1, and AOA4. Identification of biallelic pathogenic variants in SETX by molecular genetic testing confirms the diagnosis. ### Management. Treatment of manifestations: Physical therapy for disabilities resulting from peripheral neuropathy; wheelchair for mobility as needed; educational support (e.g., computer with speech recognition and special keyboard for typing) to compensate for difficulties in reading (caused by oculomotor apraxia) and in writing (caused by upper-limb ataxia). Preventions of secondary complications: A low-cholesterol diet is advised. Surveillance: Routine follow up with a neurologist. ### Genetic counseling. AOA2 is inherited in an autosomal recessive manner. Each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members and prenatal diagnosis for pregnancies at increased risk are possible if the pathogenic variants in the family have been identified. ## Diagnosis ### Suggestive Findings Ataxia with oculomotor apraxia type 2 (AOA2) should be suspected in individuals with the following clinical, laboratory, and radiographic features. Clinical features * Cerebellar ataxia * Absent or diminished tendon reflexes and later a peripheral axonal sensorimotor neuropathy (>90% of individuals) * Oculomotor apraxia (~51% of individuals) * Pyramidal signs (Plantar response is either flexor or neutral.) * Dystonic posture of the hands, choreic movements, head or postural tremor * Onset between age three and 30 years * Slow progression * Absence of cardiac involvement, cancer predisposition, and immunodeficiency; rare or absent telangiectasia * Absence of severe intellectual disability / cognitive regression * Family history consistent with autosomal recessive inheritance Laboratory features * Serum alpha-fetoprotein (AFP) concentration >20 ng/mL (normal 0-20 ng/mL) in >95% of affected individuals Note: Normal serum AFP concentration is highly variable, varies over time, and in individuals with AOA2 is lower than that usually observed in individuals with ataxia-telangiectasia [Mariani et al 2017]. * Increased serum total cholesterol concentration >5.6 mmol/L (normal value: 3.5-5.8 mmol/L) in ~50% of affected individuals [Le Ber et al 2004] * Increased serum creatine kinase (CK) concentration in some affected individuals * Elevated immunoglobulin levels (IgG and IgA) reported in several families [Gazulla et al 2010] Radiographic features. Brain MRI examination shows marked cerebellar atrophy (including cerebellar hemispheres and vermis) with relative sparing of the brain stem. Other * EMG shows signs of axonal neuropathy in 90%-100% of individuals with AOA2 [Bohlega et al 2011, H'mida-Ben Brahim et al 2011]. * Neuropathology. Nerve biopsy confirms axonal neuropathy. * Post-mortem brain examination showed marked loss of Purkinje cells as well as mild fibrous gliosis that was more severe in the vermis than in the hemispheres [Criscuolo et al 2006]. ### Establishing the Diagnosis The diagnosis of AOA2 is established in a proband with the above clinical, laboratory, and radiographic features. Identification of biallelic pathogenic variants in SETX by molecular genetic testing (see Table 1) confirms the diagnosis. Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing, multigene panel) and comprehensive genomic testing (exome sequencing, genome sequencing, exome array) depending on the phenotype. Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of AOA2 is broad, individuals with the distinctive features described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those with a phenotype indistinguishable from many other inherited disorders with ataxia are more likely to be diagnosed using genomic testing (see Option 2). #### Option 1 When the phenotypic and laboratory findings suggest the diagnosis of AOA2 molecular genetic testing approaches can include single-gene testing or use of a multigene panel: * Single-gene testing. Sequence analysis of SETX 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 only one or no pathogenic variant is found, perform gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications (see Table 1). * An ataxia multigene panel that includes SETX and other genes of interest (see Differential Diagnosis) may be considered to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For this disorder a multigene panel that also includes deletion/duplication analysis is recommended (see Table 1). For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. #### Option 2 When the phenotype is indistinguishable from many other inherited disorders characterized by ataxia, comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is the best option. Exome sequencing is most commonly used; genome sequencing is also possible. Exome array (when clinically available) may be considered if exome sequencing is not diagnostic. For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. ### Table 1. Molecular Genetic Testing Used in Ataxia with Oculomotor Apraxia Type 2 View in own window Gene 1MethodProportion of Pathogenic Variants 2 Detectable by Method SETXSequence analysis 3~80%-92% 4 Gene-targeted deletion/duplication analysis 5~8%-20% 6 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on allelic variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. Moreira et al [2004], Duquette et al [2005], Asaka et al [2006], Criscuolo et al [2006], Fogel & Perlman [2006], Lynch et al [2007], Zühlke et al [2007], Anheim et al [2008], Nicolaou et al [2008], Schöls et al [2008], Anheim et al [2009], Fogel et al [2009], Nakamura et al [2009], Bohlega et al [2011], Hammer et al [2012], Davis et al [2013], Nanetti et al [2013], Roda et al [2014], Newrick et al [2015], Pera et al [2015], Lu et al [2016] 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\. Detailed in Molecular Genetics, Pathogenic variants ## Clinical Characteristics ### Clinical Description Ataxia is the first sign of ataxia with oculomotor apraxia type 2 (AOA2) and is the major cause of disability early in the disease course. Later, peripheral sensorimotor neuropathy, particularly of the lower limbs, plays a significant role in disease progression. Cerebellar ataxia. All affected individuals, after initial normal development, show cerebellar ataxia, with slowly progressive gait imbalance. The first symptoms are recognized between age seven and 25 years (mean 14.6 years) [Anheim et al 2009, Hammer et al 2012]. In a study of ten affected individuals from Italy, age at onset ranged between three and 30 years (mean 20.3 years) [Criscuolo et al 2006]. Neuropathy. Ninety percent to 100% of individuals with AOA2 have sensorimotor neuropathy (i.e., absent or diminished tendon reflexes and sensorimotor deficit). Oculomotor apraxia. Oculomotor apraxia is present in about 51% of individuals [Anheim et al 2009]. It is characterized by a dissociation of eye-head movements in the "head-free" condition, in which the head reaches the lateral target before the eyes. In an Italian cohort, this feature was present in only 20% of individuals [Criscuolo et al 2006], while in a study of 19 affected Algerian individuals oculomotor apraxia was present in 32% [Tazir et al 2009]. A study of five individuals with AOA2, without head thrusts, revealed that hypometric saccades with a staircase pattern could be a more reliable sign of oculomotor apraxia than head thrust movements [Panouillères et al 2013]. Saccadic pursuit, gaze-evoked nystagmus, poor horizontal optokinetic nystagmus, and square-wave jerks have also been observed in several individuals [Al-Kaabi et al 2011]. In an Algerian study, 37% of affected individuals presented with convergent strabismus [Tazir et al 2009] and in a study of 90 affected individuals worldwide, strabismus was found in 12.3% [Anheim et al 2009]. Unilateral strabismus combined with nystagmus was found in an affected Algerian individual [H'mida-Ben Brahim et al 2011]. Movement disorders. Dystonic posture of the hands, choreic movements, and head or postural tremor are observed in about 14% of individuals [Anheim et al 2009, Tazir et al 2009]. The severity of the movement disorders persists in individuals with AOA2 in contrast to the movement disorder in individuals with ataxia with oculomotor apraxia type 1 (AOA1), in which chorea tends to disappear with time [Le Ber et al 2004]. In the Italian study, extrapyramidal symptoms (including choreiform head movements, truncal dystonia, and head tremor) were reported in 20% of individuals; however, they rapidly disappeared as the disease progressed [Criscuolo et al 2006]. In the French-Canadian group of individuals tremor was an inconsistent feature present in 57% [Duquette et al 2005]. Rarely, involuntary movements have been reported as a prominent presenting sign of AOA2, although they are accompanied by ataxia in almost all individuals. Two individuals had upper limb dystonia as an initial sign. Two sibs presented with prominent chorea of the trunk and face. One individual had isolated head tremor as the initial sign at age nine years [Pearson 2016]. Pyramidal signs were found in 20.5% of individuals with AOA2 [Anheim et al 2009]. Plantar response was either flexor or neutral [Koenig & Moreira 2007] Intellect. Mild cognitive impairment is present in some individuals [Le Ber et al 2004]; none have had severe intellectual disability or dementia, even after long disease duration [Le Ber et al 2004]. In the Criscuolo et al [2006] study, three of ten persons presented with mild intellectual impairment with onset around age 50 years. A study of the neuropsychological proﬁle of an individual age 45 years with AOA2 indicated that the pathogenesis of the cerebrocerebellar circuit in AOA2 was responsible for the weaker coordination of complex cognitive functions such as working memory, executive functions, speech, and sequence learning [Klivényi et al 2012]. Other. Deep sensory loss [Le Ber et al 2004, Fogel et al 2009, H'mida-Ben Brahim et al 2011], extensor plantar reflexes, swallowing difficulties, and sphincter disturbances are observed in some individuals [Le Ber et al 2004]. Various signs of extraneurologic involvement including early-onset menopause [Criscuolo et al 2006], ovarian failure [Gazulla et al 2009], dermatofibrosarcoma protuberans [Schöls et al 2008], polycystic ovarian syndrome [Fogel et al 2009], and amenorrhea secondary to hypogonadotropic hypogonadism [Anheim et al 2009] have been reported. Life span. In individuals studied to date, disease duration ranged between two and 53 years, corresponding to the maximum age of last examination, which was at 79 years. Neuropathology. Chronic axonal neuropathy with preferential loss of large (and to a lesser degree small) myelinated fibers is detected in sural nerve biopsies [Al-Kaabi et al 2011]. Postmortem brain examination in an Italian patient age 79 years who died of heart failure revealed reduction in the overall size of the brain, including atrophy of the cerebellar folia and marked widening of the sulci [Criscuolo et al 2006]. Cerebellar atrophy was most evident at the level of the vermis and the anterior lobe. The brain stem and spinal cord were slightly reduced in size without other anomalies. The substantia nigra appeared normally pigmented. Atheromatous plaques were present in all the arteries of the circle of Willis. Histologic examination showed normal cortical neurons (both in number and shape), marked loss of Purkinje cells in the cerebellar cortex, and mild fibrous gliosis that was more severe in the vermis than in the hemispheres. No inclusions or torpedos were found. The neurons of the dentate nuclei were slightly reduced in number. Chromatolysis of the oculomotor and raphe nuclei was observed in the brain stem. The inferior and accessory olives appeared relatively spared. In the spinal cord severe demyelination of the gracilis and cuneatus funiculi and degeneration of Clarke's columns with gliosis were observed. A study of 3 Tesla (3T) brain MRI examinations of five individuals with AOA2 revealed significant atrophy of all cerebellar lobules. The degree of atrophy was highest in the vermis, consistent with the oculomotor presentation, and the anterior lobe, consistent with kinetic limb ataxia. An absence of hypointensity of the iron signal on susceptibility-weighted imaging (SWI) was seen in the dentate nucleus of all affected individuals [Frismand et al 2013]. Neurochemical patterns. Short-echo, single-voxel proton ((1)H) magnetic resonance spectroscopy performed in nine individuals with AOA2 showed total N-acetylaspartate levels in the cerebellum strongly correlated with the Friedreich Ataxia Rating Scale (FARS), which may be used as a measure of impairment in those with ataxia [Iltis et al 2010]. ### Genotype-Phenotype Correlations A study of 90 individuals with AOA2 found that pathogenic missense variants in the helicase domain caused less severe AOA2 phenotypes than missense variants outside of this domain, or deletions, or truncating variants of SETX. However, individuals with pathogenic truncating or missense variants outside of the helicase domain had a lower frequency of pyramidal signs – a finding that may reflect masking of the pyramidal signs by severe motor neuropathy [Anheim et al 2009]. ### Nomenclature AOA2 was first known as "ataxia with later onset and high level of alpha-fetoprotein." ### Prevalence The prevalence of p.Leu1976Arg and p.Glu65Lys pathogenic variants was studied by genotyping 154 samples from the Gaspésie region, including 82 French-Canadian and 72 Anglo-Norman control samples [Duquette et al 2005]. In this study, five individuals (3 of Anglo-Norman and 2 of French-Canadian backgrounds) were carriers of the p.Leu1976Arg common French-Canadian variant and none was a carrier of the rarer p.Glu65Lys variant. According to these results, the carrier rate for the p.Leu1976Arg variant is estimated to be 3.5% (1:28) for Québécois of Anglo-Norman origin and 2.1% (1:47) for the French-Canadian population of Gaspésie. No individuals homozygous for the pathogenic variants p.Leu1976Arg or p.Glu65Lys were identified. A study of 102 individuals with suspected autosomal recessive cerebellar ataxia from Eastern Europe (95 from Alsace, in eastern France) reported seven individuals with AOA2 (6.9%). AOA2 prevalence in Alsace was inferred to be slightly less than 1:400,000 [Anheim et al 2010]. ## Differential Diagnosis Childhood. The diagnosis of ataxia with oculomotor apraxia type 2 (AOA2) can be difficult to establish in young children because not all features of the disease are present or apparent. AOA2 in childhood needs to be distinguished from the following disorders: * Ataxia with oculomotor apraxia type 1 (AOA1) is a progressive cerebellar ataxia characterized by childhood onset followed by oculomotor apraxia and a severe primary motor peripheral axonal motor neuropathy. The first manifestation is progressive gait imbalance (mean age of onset: 4.3 years; range: 2-10 years), followed by dysarthria, then upper-limb dysmetria with mild intention tremor. Oculomotor apraxia, usually noticed a few years after the onset of ataxia, progresses to external ophthalmoplegia. All affected individuals have generalized areflexia followed by a peripheral neuropathy and quadriplegia with loss of ambulation about seven to ten years after onset. Hands and feet are short and atrophic. Chorea and upper-limb dystonia are common. Intellect remains normal in some individuals; in others, different degrees of cognitive impairment have been observed. After a long disease duration (>10-15 years), low serum concentration of albumin and high serum concentration of total cholesterol are observed. AOA1 is caused by pathogenic variants in APTX, the gene encoding aprataxin. * Ataxia with oculomotor apraxia type 4 (AOA4) (OMIM 616267) a form of recessive ataxia characterized by mean age at onset of 4.3 years, marked extrapyramidal manifestations, rapid progression, low or normal albumin levels, normal or high cholesterol levels, and elevated alpha-fetoprotein in some individuals. AOA4 is caused by pathogenic variants in PNKP. * When oculomotor apraxia and/or high serum concentrations of alpha-fetoprotein are present, ataxia-telangiectasia (caused by pathogenic variants in ATM) and ataxia-telangiectasia-like disorder (caused by pathogenic variants in MRE11; OMIM 604391) should also be considered. Adolescence * Friedreich ataxia (FRDA) can be excluded on clinical grounds, as oculomotor apraxia is not observed in FRDA and cerebellar atrophy is not observed on MRI in FRDA early in the disease course. Molecular genetic testing of FRDA can detect pathogenic variants in virtually 100% of affected individuals. * Ataxia with vitamin E deficiency (AVED) and primary coenzyme Q10 deficiency should be considered because they are treatable disorders. Adulthood. In simplex cases (i.e., a single occurrence in a family), the possibility of spinocerebellar ataxia type 2 (SCA2) (a dominant form of ataxia which also associates cerebellar ataxia with slow eye movements) can be excluded by molecular genetic testing of SCA2. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with oculomotor apraxia type 2 (AOA2), the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended: * Neurologic examination including assessment of cranial nerve function, gait and limb ataxia, coordination, tone, strength, reflexes, and sensory perception * Ophthalmologic examination * Physical therapy and occupational therapy assessment of strength and balance * Assessment of cognitive function * Serum cholesterol * Consultation with a clinical geneticist and/or genetic counselor * Serum alpha-fetoprotein (AFP) concentration, if not evaluated previously ### Treatment of Manifestations Physical therapy may be helpful, particularly for disabilities resulting from peripheral neuropathy. A wheelchair is usually necessary for mobility by age 30 years. Educational support (e.g., use of a computer with speech recognition and special keyboard for typing) should be provided to compensate for difficulties in reading (caused by oculomotor apraxia) and in writing (caused by upper-limb ataxia). ### Prevention of Secondary Complications A low-cholesterol diet is advised to reduce the risk of adverse health effects of hypercholesterolemia ### Surveillance Routine visits to the attending neurologist are indicated. Ophthalmologic surveillance is recommended. Cholesterol level should be monitored regularly. ### 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Ataxia with Oculomotor Apraxia Type 2	c1853761	27,024	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1154/	2021-01-18T21:41:57	{"mesh": ["C537308"], "synonyms": ["AOA2"]}
Chanarin-Dorfman syndrome is a condition in which fats (lipids) are stored abnormally in the body. Affected individuals cannot break down certain fats called triglycerides, and these fats accumulate in organs and tissues, including skin, liver, muscles, intestine, eyes, and ears. People with this condition also have dry, scaly skin (ichthyosis), which is usually present at birth. Additional features of this condition include an enlarged liver (hepatomegaly), clouding of the lens of the eyes (cataracts), difficulty with coordinating movements (ataxia), hearing loss, short stature, muscle weakness (myopathy), involuntary movement of the eyes (nystagmus), and mild intellectual disability. The signs and symptoms vary greatly among individuals with Chanarin-Dorfman syndrome. Some people may have ichthyosis only, while others may have problems affecting many areas of the body. ## Frequency Chanarin-Dorfman syndrome is a rare condition; its incidence is unknown. ## Causes Mutations in the ABHD5 gene cause Chanarin-Dorfman syndrome. The ABHD5 gene provides instructions for making a protein that turns on (activates) the ATGL enzyme, which breaks down triglycerides. Triglycerides are the main source of stored energy in cells. These fats must be broken down into simpler molecules called fatty acids before they can be used for energy. ABHD5 gene mutations impair the protein's ability to activate the ATGL enzyme. An inactive enzyme makes the breakdown of triglycerides impossible, causing them to accumulate in tissues throughout the body. The buildup of triglycerides results in the signs and symptoms of Chanarin-Dorfman syndrome. ### Learn more about the gene associated with Chanarin-Dorfman syndrome * ABHD5 ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Chanarin-Dorfman syndrome	c0268238	27,025	medlineplus	https://medlineplus.gov/genetics/condition/chanarin-dorfman-syndrome/	2021-01-27T08:25:31	{"gard": ["3979"], "mesh": ["C536560"], "omim": ["275630"], "synonyms": []}
For the similar condition but where the eyes deviate inward, see esotropia. For the similar condition but where the eyes deviate outward, see exotropia. This article may be too technical for most readers to understand. Please help improve it to make it understandable to non-experts, without removing the technical details. (January 2017) (Learn how and when to remove this template message) Cyclotropia SpecialtyOphthalmology Cyclotropia is a form of strabismus in which, compared to the correct positioning of the eyes, there is a torsion of one eye (or both) about the eye's visual axis. Consequently, the visual fields of the two eyes appear tilted relative to each other. The corresponding latent condition – a condition in which torsion occurs only in the absence of appropriate visual stimuli – is called cyclophoria. Cyclotropia is often associated with other disorders of strabism, can result in double vision, and can cause other symptoms, in particular head tilt.[1] In some cases, subjective and objective cyclodeviation may result from surgery for oblique muscle disorders; if the visual system cannot compensate for it, cyclotropia and rotational double vision (cyclodiplopia) may result.[2][3] The role of cyclotropia in vision disorders is not always correctly identified. In several cases of double vision, once the underlying cyclotropia was identified, the condition was solved by surgical cyclotropia correction.[4] Conversely, artificially causing cyclotropia in cats leads to reduced vision acuity, resulting in a defect similar to strabismic amblyopia.[5] ## Contents * 1 Diagnosis * 2 Treatment * 3 References * 4 Further reading * 5 External links ## Diagnosis[edit] Cyclotropia can be detected using subjective tests such as the Maddox rod test, the Bagolini striated lens test,[6] the phase difference haploscope of Aulhorn,[6] or the Lancaster red-green test (LRGT). Among these, the LRGT is the most complete.[7] Cyclotropia can also be diagnosed using a combination of subjective and objective tests.[8][9] Before surgery, both subjective and objective torsion should be assessed.[10] Experiments have also been made on whether cyclic deviations can be assessed by purely photographic means.[11] ## Treatment[edit] If only small amounts of torsion are present, cyclotropia may be without symptoms entirely and may not need correction, as the visual system can compensate small degrees of torsion and still achieve binocular vision (see also: cyclodisparity, cyclovergence).[7][10] The compensation can be a motor response (visually evoked cyclovergence) or can take place during signal processing in the brain. In patients with cyclotropia of vascular origin, the condition often improves spontaneously.[7] Cyclotropia cannot be corrected with prism spectacles in the way other eye position disorders are corrected.[12] (Nonetheless two Dove prisms can be employed to rotate the visual field in experimental settings.) For cyclodeviations above 5 degrees, surgery has normally been recommended.[13] Depending on the symptoms, the surgical correction of cyclotropia may involve a correction of an associated vertical deviation (hyper- or hypotropia), or a Harada–Ito procedure[14] or another procedure[15] to rotate the eye inwards, or yet another procedure to rotate it outwards.[16] A cyclodeviation may thus be corrected at the same time with a correction of a vertical deviation (hyper- or hypotropia); cyclodeviations without any vertical deviation can be difficult to manage surgically, as the correction of the cyclodeviation may introduce a vertical deviation.[13] ## References[edit] 1. ^ Michael C. Brodsky (1 January 2010). Pediatric Neuro-Ophthalmology. Springer. p. 445. ISBN 978-0-387-69069-8. Retrieved 10 July 2013. 2. ^ See section "Discussion" in: Pradeep Sharma; S. Thanikachalam; Sachin Kedar; Rahul Bhola (January–February 2008). "Evaluation of subjective and objective cyclodeviation following oblique muscle weakening procedures". Indian Journal of Ophthalmology. 56 (1). pp. 39–43. doi:10.4103/0301-4738.37594. PMC 2636065. PMC 2636065. 3. ^ H. D. Schworm; S. Eithoff; M. Schaumberger; K. P. Boergen (February 1997). "Investigations on subjective and objective cyclorotatory changes after inferior oblique muscle recession". Investigative Ophthalmology & Visual Science. 38 (2). pp. 405–412. 4. ^ Burton J. Kushner (1992). "Unexpected Cyclotropia Simulating Disruption of Fusion". Archives of Ophthalmology. 110 (10). pp. 1415–1418. doi:10.1001/archopht.1992.01080220077025. 5. ^ Brian Timney; Carol K. Peck (November 1981). "Visual acuity in cats following surgically induced cyclotropia". Behavioural Brain Research. 3 (3). pp. 289–302. doi:10.1016/0166-4328(81)90001-2. 6. ^ a b G.K. von Noorden (July–August 1984). "Clinical and theoretical aspects of cyclotropia". J Pediatr Ophthalmol Strabismus. 21 (4). pp. 126–132. PMID 6470908. 7. ^ a b c S.-J. Woo; J.-M. Seo; J.-M. Hwang (2005). "Clinical". Eye (19). pp. 873–878. doi:10.1038/sj.eye.6701675. 8. ^ Zia Chaudhuri; Murugesan Vanathi, M.D. (2012). Postgraduate Ophthalmology. JP Medical Ltd. pp. 1965 ff. ISBN 978-93-5025-270-3. Retrieved 19 July 2013. 9. ^ M. Ruttum; G. K. Von Noorden (August 1984). "The Bagolini striated lens test for cyclotropia". Documenta Ophthalmologica. 58 (1). pp. 131–139. doi:10.1007/bf00140911. 10. ^ a b Phyllis E. Weingarten and David L. Guyton, Volume=6, Chapter 97: Surgery to Correct Cyclotropia Archived 2015-02-10 at the Wayback Machine 11. ^ Joost Felius; Kirsten G. Locke; Mohamed A. Hussein; David R. Stager Jr; David R. Stager Sr (December 2009). "Photographic assessment of changes in torsional strabismus". Journal of American Association for Pediatric Ophthalmology and Strabismus. 13 (6). pp. 593–595. doi:10.1016/j.jaapos.2009.09.008. 12. ^ G.K. von Noorden (July–August 1984). "Clinical and theoretical aspects of cyclotropia". J Pediatr Ophthalmol Strabismus. 21 (4). pp. 126–132. PMID 6470908. As cited by: S.-J. Woo; J.-M. Seo; J.-M. Hwang (2005). "Clinical". Eye (19). pp. 873–878. doi:10.1038/sj.eye.6701675. 13. ^ a b "The patient fixates a vertical line target, and the dove prism is rotated in the direction to increase the action of the insufficient muscle while fusion is maintained." Quoted from: Mitchell Scheiman; Bruce Wick (2008). Clinical Management of Binocular Vision: Heterophoric, Accommodative, and Eye Movement Disorders. Lippincott Williams & Wilkins. p. 432. ISBN 978-0-7817-7784-1. Retrieved 22 July 2013. 14. ^ Ka Hee Park; Jin Hee Shin; So Young Kim (April 2012). "Surgical Results of Modified Harada-Ito Operation for Excyclotorsion". Journal of the Korean Ophthalmological Society. 53 (4). 15. ^ Genjiro Ohmi; Takashi Fujikado; Masahito Ohji; Yoshihiro Saito; Yasuo Tano (January 1997). "Horizontal transposition of vertical rectus muscles for treatment of excyclotropia". Graefe's Archive for Clinical and Experimental Ophthalmology. 235 (1). pp. 1–4. doi:10.1007/bf01007829. 16. ^ 2.22 Cyclotropia: Treatment, ORBIS Telemedicine (downloaded 19 July 2013) ## Further reading[edit] * Lemos, João; Eggenberger, Eric: Clinical utility and assessment of cyclodeviation, Current Opinion in Ophthalmology, November 2013, Volume 24, Issue 6, pp. 558–565 doi:10.1097/ICU.0000000000000003 ## External links[edit] Classification D * ICD-10: H50.4 * ICD-10-CM: H50.41 * ICD-9-CM: 378.33 * SNOMED CT: 70486007 * v * t * e * Diseases of the human eye Adnexa Eyelid Inflammation * Stye * Chalazion * Blepharitis * Entropion * Ectropion * Lagophthalmos * Blepharochalasis * Ptosis * Blepharophimosis * Xanthelasma * Ankyloblepharon Eyelash * Trichiasis * Madarosis Lacrimal apparatus * Dacryoadenitis * Epiphora * Dacryocystitis * Xerophthalmia Orbit * Exophthalmos * Enophthalmos * Orbital cellulitis * Orbital lymphoma * Periorbital cellulitis Conjunctiva * Conjunctivitis * allergic * Pterygium * Pseudopterygium * Pinguecula * Subconjunctival hemorrhage Globe Fibrous tunic Sclera * Scleritis * Episcleritis Cornea * Keratitis * herpetic * acanthamoebic * fungal * Exposure * Photokeratitis * Corneal ulcer * Thygeson's superficial punctate keratopathy * Corneal dystrophy * Fuchs' * Meesmann * Corneal ectasia * Keratoconus * Pellucid marginal degeneration * Keratoglobus * Terrien's marginal degeneration * Post-LASIK ectasia * Keratoconjunctivitis * sicca * Corneal opacity * Corneal neovascularization * Kayser–Fleischer ring * Haab's striae * Arcus senilis * Band keratopathy Vascular tunic * Iris * Ciliary body * Uveitis * Intermediate uveitis * Hyphema * Rubeosis iridis * Persistent pupillary membrane * Iridodialysis * Synechia Choroid * Choroideremia * Choroiditis * Chorioretinitis Lens * Cataract * Congenital cataract * Childhood cataract * Aphakia * Ectopia lentis Retina * Retinitis * Chorioretinitis * Cytomegalovirus retinitis * Retinal detachment * Retinoschisis * Ocular ischemic syndrome / Central retinal vein occlusion * Central retinal artery occlusion * Branch retinal artery occlusion * Retinopathy * diabetic * hypertensive * Purtscher's * of prematurity * Bietti's crystalline dystrophy * Coats' disease * Sickle cell * Macular degeneration * Retinitis pigmentosa * Retinal haemorrhage * Central serous retinopathy * Macular edema * Epiretinal membrane (Macular pucker) * Vitelliform macular dystrophy * Leber's congenital amaurosis * Birdshot chorioretinopathy Other * Glaucoma / Ocular hypertension / Primary juvenile glaucoma * Floater * Leber's hereditary optic neuropathy * Red eye * Globe rupture * Keratomycosis * Phthisis bulbi * Persistent fetal vasculature / Persistent hyperplastic primary vitreous * Persistent tunica vasculosa lentis * Familial exudative vitreoretinopathy Pathways Optic nerve Optic disc * Optic neuritis * optic papillitis * Papilledema * Foster Kennedy syndrome * Optic atrophy * Optic disc drusen Optic neuropathy * Ischemic * anterior (AION) * posterior (PION) * Kjer's * Leber's hereditary * Toxic and nutritional Strabismus Extraocular muscles Binocular vision Accommodation Paralytic strabismus * Ophthalmoparesis * Chronic progressive external ophthalmoplegia * Kearns–Sayre syndrome palsies * Oculomotor (III) * Fourth-nerve (IV) * Sixth-nerve (VI) Other strabismus * Esotropia / Exotropia * Hypertropia * Heterophoria * Esophoria * Exophoria * Cyclotropia * Brown's syndrome * Duane syndrome Other binocular * Conjugate gaze palsy * Convergence insufficiency * Internuclear ophthalmoplegia * One and a half syndrome Refraction * Refractive error * Hyperopia * Myopia * Astigmatism * Anisometropia / Aniseikonia * Presbyopia Vision disorders Blindness * Amblyopia * Leber's congenital amaurosis * Diplopia * Scotoma * Color blindness * Achromatopsia * Dichromacy * Monochromacy * Nyctalopia * Oguchi disease * Blindness / Vision loss / Visual impairment Anopsia * Hemianopsia * binasal * bitemporal * homonymous * Quadrantanopia subjective * Asthenopia * Hemeralopia * Photophobia * Scintillating scotoma Pupil * Anisocoria * Argyll Robertson pupil * Marcus Gunn pupil * Adie syndrome * Miosis * Mydriasis * Cycloplegia * Parinaud's syndrome Other * Nystagmus * Childhood blindness Infections * Trachoma * Onchocerciasis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Cyclotropia	c0152209	27,026	wikipedia	https://en.wikipedia.org/wiki/Cyclotropia	2021-01-18T18:59:04	{"umls": ["C0152209"], "wikidata": ["Q17085142"]}
An extremely rare form of bone dysplasia characterized by the features of osteogenesis imperfecta such as bone fragility associated with multiple fractures, bone deformities (metaphyseal irregularities and bowing of the long bones) and blue sclera, in association with growth failure, craniosynostosis, hydrocephalus, ocular proptosis, and distinctive facial features (e.g. frontal bossing, midface hypoplasia, and micrognathia). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Cole-Carpenter syndrome	c1862178	27,027	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2050	2021-01-23T18:43:52	{"gard": ["1425"], "mesh": ["C535963"], "omim": ["112240", "616294"], "umls": ["C1862178"], "icd-10": ["Q78.0"], "synonyms": ["Bone fragility-craniosynostosis-proptosis-hydrocephalus syndrome"]}
Neuronal intestinal pseudoobstruction is a form of chronic intestinal pseudoobstruction caused by a developmental failure of the enteric neurons to differentiate or migrate properly and manifests as a bowel obstruction. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Neuronal intestinal pseudoobstruction	c1855733	27,028	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99811	2021-01-23T18:02:15	{"mesh": ["C537394"], "omim": ["243185"], "umls": ["C1855733"], "icd-10": ["K59.8"]}
Exercise-induced anaphylaxis (EIAn) is a rare disorder in which anaphylaxis occurs in association with physical activity. Food-dependent exercise-induced anaphylaxis is a subset of this disorder in which symptoms develop if exertion takes place within a few hours of eating a specific food. In the case of food-dependent exercise-induced anaphylaxis, neither the food nor the exercise alone is enough to cause anaphylaxis. Vigorous forms of physical activity, such as jogging, are more commonly associated with exercise-induced anaphylaxis, although lower levels of exertion (eg, walking and yard work) are also capable of triggering attacks. However, the condition can be unpredictable; a given level of exercise may cause an episode on one occasion but not another. Symptoms of exercise-induced anaphylaxis may include itching, hives (urticaria), flushing, extreme fatigue, and wheezing. Affected individuals may also experience nausea, abdominal cramping, and diarrhea. Continuing the physical activity causes the symptoms to become worse. However, if the individual stops the activity when the symptoms first appear, there is usually improvement within minutes. In most cases, these conditions are sporadic , though familial cases have been reported. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Exercise-induced anaphylaxis	c0344183	27,029	gard	https://rarediseases.info.nih.gov/diseases/6392/exercise-induced-anaphylaxis	2021-01-18T18:00:38	{"umls": ["C0344183"], "synonyms": []}
Septic thrombophlebitis Septic thrombophlebitis refers to venous thrombosis and inflammation associated with bacteremia. ## Contents * 1 Causes * 2 Diagnosis * 3 Treatment * 4 See also * 5 References * 6 External links ## Causes[edit] It can occur following throat infections, dental procedures, gingivitis, or central lines.[1] Following pregnancy septic pelvic thrombophlebitis may occur.[2] ## Diagnosis[edit] This section is empty. You can help by adding to it. (September 2017) ## Treatment[edit] Treatment is mainly antibiotic and may involve heparin.[3] ## See also[edit] * Superficial thrombophlebitis * List of cutaneous conditions ## References[edit] 1. ^ Kar, S; Webel, R (2014). "Septic thrombophlebitis: percutaneous mechanical thrombectomy and thrombolytic therapies". American Journal of Therapeutics. 21 (2): 131–6. doi:10.1097/mjt.0b013e31822de6e3. PMID 22198069. 2. ^ Garcia J, Aboujaoude R, Apuzzio J, Alvarez JR (2006). "Septic pelvic thrombophlebitis: diagnosis and management". Infect Dis Obstet Gynecol. 2006: 15614. doi:10.1155/IDOG/2006/15614. PMC 1581461. PMID 17485796. 3. ^ "Thrombophlebitis, Septic: eMedicine Emergency Medicine". Retrieved 2010-03-28. ## External links[edit] Classification D * ICD-10: Xxx.x * ICD-9-CM: xxx External resources * eMedicine: article/786526 This dermatology article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Septic thrombophlebitis	c0740341	27,030	wikipedia	https://en.wikipedia.org/wiki/Septic_thrombophlebitis	2021-01-18T19:05:08	{"umls": ["C0740341"], "wikidata": ["Q16977356"]}
Wartenberg's migratory sensory neuropathy SpecialtyNeurology Wartenberg's migratory sensory neuropathy (also known as Wartenberg's migrant sensory neuritis) affects the cutaneous nerves.[1] A benign, relapsing and remitting condition involving pain, numbness and paresthesias in the sensory and peripheral nerves. ## References[edit] 1. ^ Katirji, Bashar; Kaminski, Henry J.; Ruff, Robert L. (2013). Neuromuscular Disorders in Clinical Practice. Springer Science & Business Media. p. 743. ISBN 9781461465676. 2\. http://www.partialobserver.com/Wartenberg.cfm 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Wartenberg's migratory sensory neuropathy	None	27,031	wikipedia	https://en.wikipedia.org/wiki/Wartenberg%27s_migratory_sensory_neuropathy	2021-01-18T18:48:00	{"wikidata": ["Q3338687"]}
Hyalinizing clear cell carcinoma Micrograph of a hyalinizing clear cell carcinoma showing the characteristic clear cells and surrounding hyalinized stroma. H&E stain. SpecialtyOncology, ENT surgery Hyalinizing clear cell carcinoma (HCCC) is a rare malignant salivary gland tumour, with a good prognosis, that is usually found on the tongue or palate.[1] ## Contents * 1 Signs and symptoms * 2 Diagnosis * 2.1 Pathology * 3 Prognosis * 4 See also * 5 References ## Signs and symptoms[edit] HCCCs typically present as a painless mass in the mouth.[2] ## Diagnosis[edit] HCCCs are diagnosed by examination of tissue, e.g. a biopsy. ### Pathology[edit] HCCC consist of cells with abundant clear cytoplasm, arranged in cords, trabeculae or clusters in a hyalinized stroma.[3] Nuclear pleomorphism is usually minimal and mitoses are infrequently seen.[2] Owing to their glycogen content, which explains the "clear" appearance under the microscope, tumour cells stain with PAS. Immunostains for S100 and smooth muscle actin (SMA) are typically negative, but positive for cytokeratins and epithelial membrane antigen (EMA). HCCCs typically have a recurrent chromosomal translocation, t(12;22), involving the genes EWSR1 and ATF1.[4] The same translocation is seen in clear cell sarcoma. The histologic differential diagnosis includes mucoepidermoid carcinoma (clear cell variant), acinic cell carcinoma (clear cell variant), epithelial-myoepithelial carcinoma and metastatic clear cell carcinoma. * Intermed. mag. * Very high mag. ## Prognosis[edit] They generally have a good prognosis.[5] ## See also[edit] * Clear cell renal cell carcinoma ## References[edit] 1. ^ Kauzman, A.; Tabet, JC.; Stiharu, TI. (Jul 2011). "Hyalinizing clear cell carcinoma: a case report and review of the literature". Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 112 (1): e26–34. doi:10.1016/j.tripleo.2011.02.041. PMID 21669357. 2. ^ a b Milchgrub, S.; Gnepp, DR.; Vuitch, F.; Delgado, R.; Albores-Saavedra, J. (Jan 1994). "Hyalinizing clear cell carcinoma of salivary gland". Am J Surg Pathol. 18 (1): 74–82. doi:10.1097/00000478-199401000-00007. PMID 7506496. 3. ^ O'Sullivan-Mejia, ED.; Massey, HD.; Faquin, WC.; Powers, CN. (Sep 2009). "Hyalinizing clear cell carcinoma: report of eight cases and a review of literature". Head Neck Pathol. 3 (3): 179–85. doi:10.1007/s12105-009-0124-3. PMC 2811632. PMID 20596970. 4. ^ Antonescu, CR.; Katabi, N.; Zhang, L.; Sung, YS.; Seethala, RR.; Jordan, RC.; Perez-Ordoñez, B.; Have, C.; et al. (Jul 2011). "EWSR1-ATF1 fusion is a novel and consistent finding in hyalinizing clear-cell carcinoma of salivary gland". Genes Chromosomes Cancer. 50 (7): 559–70. doi:10.1002/gcc.20881. PMID 21484932. 5. ^ Masilamani, S.; Rao, S.; Chirakkal, P.; Kumar, AR. (2011). "Hyalinizing clear cell carcinoma of the base of tongue: a distinct and rare entity". Indian J Pathol Microbiol. 54 (1): 167–9. doi:10.4103/0377-4929.77393. PMID 21393908. * v * t * e Tumors of lip, oral cavity and pharynx / head and neck cancer Oral cancer Salivary gland malignant epithelial tumors * Acinic cell carcinoma * Mucoepidermoid carcinoma * Adenoid cystic carcinoma * Salivary duct carcinoma * Epithelial-myoepithelial carcinoma * Polymorphous low-grade adenocarcinoma * Hyalinizing clear cell carcinoma benign epithelial tumors * Pleomorphic adenoma * Warthin's tumor ungrouped: * Oncocytoma Tongue * Leukoplakia * Rhabdomyoma * Oropharynx [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Hyalinizing clear cell carcinoma	None	27,032	wikipedia	https://en.wikipedia.org/wiki/Hyalinizing_clear_cell_carcinoma	2021-01-18T18:57:10	{"wikidata": ["Q5952492"]}
A number sign (#) is used with this entry because of evidence that pulmonary alveolar microlithiasis is caused by homozygous mutation in the gene encoding type IIb sodium-phosphate cotransporter (SLC34A2; 604217), which is involved in phosphate homeostasis in several organs, on chromosome 4p15. Description Pulmonary alveolar microlithiasis is a rare disease characterized by the deposition of calcium phosphate microliths throughout the lungs. Most patients are asymptomatic for several years or even for decades, and, generally, the diagnosis is incidental to clinical investigations unrelated to the specific disorder. Cases with early onset or rapid progression are rare. A 'sandstorm-appearing' chest roentgenogram is a typical diagnostic finding. The onset of this potentially lethal disease varies from the neonatal period to old age, and the disease follows a long-term progressive course, resulting in a slow deterioration of lung functions. About one-third of the reported cases are said to be familial (summary by Corut et al., 2006). Clinical Features Pulmonary alveolar microlithiasis is characterized by multiple minute calcifications located in the alveoli that produce a typical radiographic appearance. Castellana et al. (2002) reviewed the over 300 individuals reported with pulmonary alveolar microlithiasis. The age at clinical onset was highly variable (5-41 years), and there was a great discrepancy between radiologic features and clinical symptoms. The age range at diagnosis was wide, but usually occurred between the ages of 20 and 30 years. The condition usually evolved over 10 to 20 years and was sometimes very indolent. Brandenburg and Schubert (2003) presented the radiographic features of a 28-year-old patient with the disorder. Despite the striking radiographic changes with nodular ('sandstorm-like') calcifications in the lungs, the patient had only mild pleuritic chest pain. A hallmark of the disorder is a striking dissociation between the radiologic findings and the mild clinical signs and symptoms. Ritchie et al. (1992) found pulmonary alveolar microlithiasis in a 5-year-old boy being investigated for multiple exostoses (133700). Neither disorder was identified in other members of the immediate family. Senyigit et al. (2001) described this disorder in 6 males in 1 family. Five of the patients were cousins, and the other patient was their uncle. The diagnosis was based on the demonstration of microliths by bronchoalveolar lavage in 5 patients and transbronchial biopsy in 1. Inheritance Family studies are consistent with autosomal recessive inheritance (Castellana et al., 2002). Caffrey and Altman (1965) described the disorder in premature twins who died at age 12 hours and reviewed 66 reported cases. Thirty-four cases, including theirs, were familial, occurring in 13 families. In Spain, Lopez-Areal et al. (1965) described 2 affected sisters in 1 family, and a boy and his 2 sisters in another. O'Neill et al. (1967) observed 3 affected sibs. Affected brother and sister with first-cousin parents were reported by Burguet and Reginster (1967). In Beirut, Balikian et al. (1968) described the disorder in 2 pairs of brothers and an unrelated girl. Population Genetics Ucan et al. (1993) stated that only 173 cases of this disorder had been reported worldwide, and that the condition is unusually common in Turkey. They reported 52 Turkish cases, 49 of which had previously been described only in Turkish publications. A positive family history was noted in 19 of 39 patients. All the familial cases were sibs except for 3 who had a maternal aunt/nephew relationship. Of the 52 cases, 10 were free of symptoms. Ucan et al. (1993) found that the cases reported in the Turkish literature between 1962 and 1993 constituted 23% of all 225 cases published world wide up to that time. In addition, some of the patients reported from other countries in the following years were of Turkish descent. Senyigit et al. (2001) pointed out that a considerable percentage of cases of this disorder have been reported from Turkey. Molecular Genetics Using homozygosity mapping in the family reported by Senyigit et al. (2001), Corut et al. (2006) mapped a locus for pulmonary alveolar microlithiasis to 4p15.31-p15.2. By a candidate gene approach they chose to investigate SLC34A2, which encodes the type IIb sodium-phosphate cotransporter (604217). They identified 6 homozygous exonic mutations in the SLC34A2 gene in 7 unrelated patients with the disorder. Absence of functional protein product of the gene was considered compatible with calcium phosphate deposition in alveolar airspaces. Thus, Corut et al. (2006) demonstrated that impaired activity of the phosphate transporter is presumably responsible for the microliths, and pulmonary alveolar microlithiasis is a recessive monogenic disease with full penetrance. History Castellana et al. (2002) stated that pulmonary alveolar microlithiasis was first described by Puhr (1933). INHERITANCE \- Autosomal recessive RESPIRATORY Lung \- Intraalveolar nodular calcifications ('microliths') \- Diffuse, bilateral medial and basal lung involvement \- Progressive pulmonary function impairment \- Pulmonary function tests show restrictive deficit \- Progressive fibrosis may occur MISCELLANEOUS \- Variable age at onset (usually 20 to 30 years of age) \- Slowly progressive MOLECULAR BASIS \- Caused by mutation in the solute carrier family 34 (sodium/phosphate cotransporter), member 2 gene (SLC34A2, 604217.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	PULMONARY ALVEOLAR MICROLITHIASIS	c0155912	27,033	omim	https://www.omim.org/entry/265100	2019-09-22T16:23:03	{"doid": ["12117"], "mesh": ["C562405"], "omim": ["265100"], "icd-9": ["516.2"], "icd-10": ["J84.02"], "orphanet": ["60025"]}
Lung abscess Computed tomography (CT) scan of chest showing bilateral pneumonia with abscesses, effusions, and caverns. 37-year-old male. SpecialtyInfectious disease, respirology Lung abscess is a type of liquefactive necrosis of the lung tissue and formation of cavities (more than 2 cm)[1] containing necrotic debris or fluid caused by microbial infection. This pus-filled cavity is often caused by aspiration, which may occur during anesthesia, sedation, or unconsciousness from injury. Alcoholism is the most common condition predisposing to lung abscesses. Lung abscess is considered primary (60%[2]) when it results from existing lung parenchymal process and is termed secondary when it complicates another process e.g. vascular emboli or follows rupture of extrapulmonary abscess into lung. ## Contents * 1 Signs and symptoms * 1.1 Complications * 2 Causes * 3 Diagnosis * 3.1 Imaging studies * 3.2 Laboratory studies * 4 Management * 5 Prognosis * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] Onset of symptoms is often gradual, but in necrotizing staphylococcal or gram-negative bacillary pneumonias patients can be acutely ill. Cough, fever with shivering, and night sweats are often present. Cough can be productive of foul smelling purulent mucus (≈70%) or less frequently with blood in one third of cases).[3] Affected individuals may also complain of chest pain, shortness of breath, lethargy and other features of chronic illness.[citation needed] Those with a lung abscess are generally cachectic at presentation. Finger clubbing is present in one third of patients.[3] Dental decay is common especially in alcoholics and children. On examination of the chest there will be features of consolidation such as localized dullness on percussion and bronchial breath sounds. ### Complications[edit] This section needs expansion. You can help by adding to it. (June 2018) Although rare in modern times, can include spread of infection to other lung segments, bronchiectasis, empyema, and bacteremia with metastatic infection such as brain abscess.[2] ## Causes[edit] Conditions contributing to lung abscess * Aspiration of oropharyngeal or gastric secretion * Septic emboli * Necrotizing pneumonia[4] * Vasculitis: Granulomatosis with polyangiitis * Necrotizing tumors: 8% to 18% are due to neoplasms across all age groups, higher in older people; primary squamous carcinoma of the lung is the most common. Organisms In the post-antibiotic era pattern of frequency is changing. In older studies anaerobes were found in up to 90% cases but they are much less frequent now.[5] * Anaerobic bacteria: Actinomyces, Peptostreptococcus, Bacteroides, Fusobacterium species, * Microaerophilic streptococcus : Streptococcus milleri * Aerobic bacteria: Staphylococcus, Klebsiella, Haemophilus, Pseudomonas, Nocardia, Escherichia coli, Streptococcus, Mycobacteria[6] * * Fungi: Candida, Aspergillus * Parasites: Entamoeba histolytica ## Diagnosis[edit] ### Imaging studies[edit] Lung abscesses are often on one side and single involving posterior segments of the upper lobes and the apical segments of the lower lobes as these areas are gravity dependent when lying down. Presence of air-fluid levels implies rupture into the bronchial tree or rarely growth of gas forming organism.[citation needed] ### Laboratory studies[edit] Raised inflammatory markers (high ESR, CRP) are common but nonspecific. Examination of the coughed up mucus is important in any lung infection and often reveals mixed bacterial flora. Transtracheal or transbronchial (via bronchoscopy) aspirates can also be cultured. Fiber optic bronchoscopy is often performed to exclude obstructive lesion; it also helps in bronchial drainage of pus.[citation needed] * Pulmonary abscess on CT scan * Pulmonary abscess on CXR * Pathology image of a lung abscess. * A subpleural abscess. ## Management[edit] Broad spectrum antibiotic to cover mixed flora is the mainstay of treatment. Pulmonary physiotherapy and postural drainage are also important. Surgical procedures are required in selective patients for drainage or pulmonary resection. The treatment is divided according to the type of abscess acute or chronic if it's acute the treatment is a- antibiotics: if anaerobic -> metronidazole or clindamycin if aerobic-> B-lactams, cephalosporins if MRSA or Staph infection -> vancomycin or linezolide b- postural drainage and chest physiotherapy c- bronchoscopy: is used for the following cases: 1-aspiration or instillation of antibiotics 2- patients with atypical presentation suspected of having underlying foreign body or malignancy[citation needed] ## Prognosis[edit] Most cases respond to antibiotics and prognosis is usually excellent unless there is a debilitating underlying condition. Mortality from lung abscess alone is around 5% and is improving.[citation needed] ## See also[edit] * Empyema * Bronchiectasis * Abscess * Pleural effusion ## References[edit] 1. ^ Bartlett JG, Finegold SM (1972). "Anaerobic pleuropulmonary infections". Medicine (Baltimore). 51 (6): 413–50. doi:10.1097/00005792-197211000-00001. PMID 4564416. 2. ^ a b "Pneumonia and Other Pulmonary Infections: Lung Abscess, Medscape". Archived from the original on 2008-03-21. Retrieved 2007-06-20. 3. ^ a b Moreira Jda S, Camargo Jde J, Felicetti JC, Goldenfun PR, Moreira AL, Porto Nda S (2006). "Lung abscess: analysis of 252 consecutive cases diagnosed between 1968 and 2004". Jornal Brasileiro de Pneumologia. 32 (2): 136–43. doi:10.1590/S1806-37132006000200009. PMID 17273583. 4. ^ Tamparo, Carol (2011). Fifth Edition: Diseases of the Human Body. Philadelphia, PA: F. A. Davis Company. p. 367. ISBN 978-0-8036-2505-1. 5. ^ Bartlett JG (2005). "The role of anaerobic bacteria in lung abscess". Clin. Infect. Dis. 40 (7): 923–5. doi:10.1086/428586. PMID 15824980. 6. ^ Hirshberg B, Sklair-Levi M, Nir-Paz R, Ben-Sira L, Krivoruk V, Kramer MR (1999). "Factors predicting mortality of patients with lung abscess". Chest. 115 (3): 746–50. doi:10.1378/chest.115.3.746. PMID 10084487. ## External links[edit] Classification D * ICD-10: J85 * ICD-9-CM: 513.x * MeSH: D008169 * DiseasesDB: 7607 External resources * eMedicine: med/1332 * v * t * e Diseases of the respiratory system Upper RT (including URTIs, common cold) Head sinuses Sinusitis nose Rhinitis Vasomotor rhinitis Atrophic rhinitis Hay fever Nasal polyp Rhinorrhea nasal septum Nasal septum deviation Nasal septum perforation Nasal septal hematoma tonsil Tonsillitis Adenoid hypertrophy Peritonsillar abscess Neck pharynx Pharyngitis Strep throat Laryngopharyngeal reflux (LPR) Retropharyngeal abscess larynx Croup Laryngomalacia Laryngeal cyst Laryngitis Laryngopharyngeal reflux (LPR) Laryngospasm vocal cords Laryngopharyngeal reflux (LPR) Vocal fold nodule Vocal fold paresis Vocal cord dysfunction epiglottis Epiglottitis trachea Tracheitis Laryngotracheal stenosis Lower RT/lung disease (including LRTIs) Bronchial/ obstructive acute Acute bronchitis chronic COPD Chronic bronchitis Acute exacerbation of COPD) Asthma (Status asthmaticus Aspirin-induced Exercise-induced Bronchiectasis Cystic fibrosis unspecified Bronchitis Bronchiolitis Bronchiolitis obliterans Diffuse panbronchiolitis Interstitial/ restrictive (fibrosis) External agents/ occupational lung disease Pneumoconiosis Aluminosis Asbestosis Baritosis Bauxite fibrosis Berylliosis Caplan's syndrome Chalicosis Coalworker's pneumoconiosis Siderosis Silicosis Talcosis Byssinosis Hypersensitivity pneumonitis Bagassosis Bird fancier's lung Farmer's lung Lycoperdonosis Other * ARDS * Combined pulmonary fibrosis and emphysema * Pulmonary edema * Löffler's syndrome/Eosinophilic pneumonia * Respiratory hypersensitivity * Allergic bronchopulmonary aspergillosis * Hamman-Rich syndrome * Idiopathic pulmonary fibrosis * Sarcoidosis * Vaping-associated pulmonary injury Obstructive / Restrictive Pneumonia/ pneumonitis By pathogen * Viral * Bacterial * Pneumococcal * Klebsiella * Atypical bacterial * Mycoplasma * Legionnaires' disease * Chlamydiae * Fungal * Pneumocystis * Parasitic * noninfectious * Chemical/Mendelson's syndrome * Aspiration/Lipid By vector/route * Community-acquired * Healthcare-associated * Hospital-acquired By distribution * Broncho- * Lobar IIP * UIP * DIP * BOOP-COP * NSIP * RB Other * Atelectasis * circulatory * Pulmonary hypertension * Pulmonary embolism * Lung abscess Pleural cavity/ mediastinum Pleural disease * Pleuritis/pleurisy * Pneumothorax/Hemopneumothorax Pleural effusion Hemothorax Hydrothorax Chylothorax Empyema/pyothorax Malignant Fibrothorax Mediastinal disease * Mediastinitis * Mediastinal emphysema Other/general * Respiratory failure * Influenza * Common cold * SARS * Coronavirus disease 2019 * Idiopathic pulmonary haemosiderosis * Pulmonary alveolar proteinosis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Lung abscess	c0024110	27,034	wikipedia	https://en.wikipedia.org/wiki/Lung_abscess	2021-01-18T19:09:29	{"mesh": ["D008169"], "wikidata": ["Q1877550"]}
Pores in one of the structures of the glomerular filtration barrier Shrunken pore syndrome (SPS) is a kidney disorder described in 2015 in which the pores in the glomerular filtration barrier are hypothesized to have shrunken so that the glomerular filtration rate (GFR) of 5–30 kDa proteins, for example cystatin C, is selectively reduced compared to that of small molecules (less than 5 kDa) such as water and creatinine.[1] The syndrome is associated with premature death.[1][2] SPS has been identified in children.[1] ## Contents * 1 Mechanism * 2 Diagnosis * 3 Prognosis * 4 References ## Mechanism[edit] Glomerulus and Bowman's capsule. The blood filtered through the glomerular filtration barrier corresponds to the primary urine collected in the Bowman's capsule. The figure compares the glomerular barrier in kidneys with and without shrunken pore syndrome It has been speculated that SPS is both caused by, and exacerbates, cardiovascular disease.[1] It was stated in 2014 that the kidneys have a role in maintaining the equilibrium between production and catabolism of most proteins between about 5 and 30 kDa in molecular mass and that failure to do so results in serious disease and strongly increased mortality, when the kidney disorder shrunken pore syndrome was identified.[1][2] Proteins less than 30 kDa comprise about 36% of the total human proteome.[1] A hypothesis concerning the pathophysiology of SPS is that several 5–30 kDa proteins with signalling functions, for example cytokines, are increased in concentration and promote development of serious disorders like cancer and cardiovascular disorders.[1] ## Diagnosis[edit] An eGFRcystatin C/eGFRcreatinine-ratio <0.60, or <0.70, in the absence of non-renal influences on eGFRcystatin C or eGFRcreatinine, identifies a condition as SPS.[1] Optimal classification and stratification of chronic kidney disease requires not only analysis of GFR (estimated or measured) and albuminuria, but also determination of the eGFRcystatin C/eGFRcreatinine-ratio to assess the presence of SPS.[1] ## Prognosis[edit] The mortality of SPS is higher than that of cancer, diabetes mellitus, cardiovascular disease or chronic kidney disease.[1] ## References[edit] 1. ^ a b c d e f g h i j Grubb A (Sep 2020). "Shrunken pore syndrome – a common kidney disorder with high mortality. Diagnosis, prevalence, pathophysiology and treatment options". Clinical Biochemistry (Review). 83: 12–20. doi:10.1016/j.clinbiochem.2020.06.002. PMID 32544475. 2. ^ a b Zhou H, Yang M, He X, Xu N (Nov 2019). "eGFR, cystatin C and creatinine in shrunken pore syndrome". Clinica Chimica Acta (Review). 498: 1–5. doi:10.1016/j.cca.2019.08.001. PMID 31398310. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Shrunken pore syndrome	None	27,035	wikipedia	https://en.wikipedia.org/wiki/Shrunken_pore_syndrome	2021-01-18T18:40:21	{"wikidata": ["Q98266891"]}
A rare congenital knee dislocation characterized by hyperextension of the knee greater than 0° associated with limited flexion, with prominence of the femoral condyles in the popliteal fossa and increased transverse skin folds over the anterior surface of the knee. It can be unilateral or bilateral and may occur as an isolated malformation, be associated with other orthopedic abnormalities (like developmental dysplasia of the hip or clubfoot) or be part of a syndrome (e. g. Larsen's syndrome). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Congenital genu recurvatum	c0152235	27,036	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=295229	2021-01-23T17:05:21	{"umls": ["C0152235"], "icd-10": ["Q68.2"]}
For a phenotypic description and a discussion of genetic heterogeneity of infantile hypertrophic pyloric stenosis (IHPS), see 179010. Inheritance Despite well-documented evidence of multifactorial inheritance of IHPS, multigenerational families consistent with autosomal dominant transmission of the disease have also been described (Finsen, 1979; Fried et al., 1981). Capon et al. (2006) analyzed a 3-generation family with IHPS including 10 affected individuals (5 males and 5 females) in 3 generations and 4 sibships in a pattern consistent with autosomal dominant inheritance. Mapping By means of an SNP-based genomewide scan in a family segregating infantile hypertrophic pyloric stenosis, Capon et al. (2006) mapped the underlying disease locus to 16p13-p12 (lod score = 3.23). The analysis of 10 additional multiplex pedigrees yielded negative or nonsignificant lod scores, indicating locus heterogeneity. Sequence analysis for candidate genes from the chromosome 16 disease interval excluded the presence of pathogenic mutations in the GRIN2A (138253) and MYH11 (160745) genes. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	PYLORIC STENOSIS, INFANTILE HYPERTROPHIC, 2	c1853228	27,037	omim	https://www.omim.org/entry/610260	2019-09-22T16:04:46	{"mesh": ["C565208"], "omim": ["610260"]}
## Clinical Features Schmid et al. (2006) reported a 7-generation family segregating X-linked endothelial corneal dystrophy. Thirty-five trait carriers were identified in 4 generations. Nine male patients demonstrated severe corneal opacifications: 2 had congenital corneal clouding in the form of a ground glass, milky appearance, and 7 had subepithelial band keratopathies combined with endothelial changes resembling moon craters. Twenty-two female and 4 male patients had only moon crater-like endothelial alterations. No male-to-male transmission was observed. Light and electron microscopy showed focal discontinuities, degeneration of the endothelial cell layer, and marked thickening of the Descemet membrane. Mapping By multipoint linkage analysis in a large family segregating endothelial corneal dystrophy, Schmid et al. (2006) found linkage of the disorder to Xq25, between markers DXS8057 and DXS1047 (maximum lod score of 10.90). INHERITANCE \- X-linked dominant HEAD & NECK Eyes \- Corneal clouding, congenital \- Late subepithelial band keratopathy \- Endothelial changes resembling lunar craters (in carrier females and some affected males) \- Discontinuity and degeneration of the endothelial cell layer \- Marked thickening of Descemet membrane ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	CORNEAL DYSTROPHY, ENDOTHELIAL, X-LINKED	c2749049	27,038	omim	https://www.omim.org/entry/300779	2019-09-22T16:19:35	{"doid": ["0060446"], "mesh": ["C567587"], "omim": ["300779"], "orphanet": ["293621"], "synonyms": ["Alternative titles", "ENDOTHELIAL CORNEAL DYSTROPHY, X-LINKED"]}
Papillitis SpecialtyOphthalmology Optic papillitis is a specific type of optic neuritis. Inflammation of the optic nerve head is called "papillitis" or "intraocular optic neuritis"; inflammation of the orbital portion of the nerve is called "retrobulbar optic neuritis" or "orbital optic neuritis".[1] It is often associated with substantial losses in visual fields, pain on moving the globe, and sensitivity to light pressure on the globe. It is often an early sign of multiple sclerosis.[2] Papillitis may have the same appearance as papilledema. However, papillitis may be unilateral, whereas papilledema is almost always bilateral. Papillitis can be differentiated from papilledema by an afferent pupillary defect (Marcus Gunn pupil), by its greater effect in decreasing visual acuity and color vision, and by the presence of a central scotoma. Papilledema that is not yet chronic will not have as dramatic an effect on vision. Because increased intracranial pressure can cause both papilledema and a sixth (abducens) nerve palsy, papilledema can be differentiated from papillitis if esotropia and loss of abduction are also present. However, esotropia may also develop secondarily in an eye that has lost vision from papillitis. Retrobulbar neuritis, an inflamed optic nerve, but with a normal-appearing nerve head, is associated with pain and the other findings of papillitis. Pseudopapilledema is a normal variant of the optic disk, in which the disk appears elevated, with indistinct margins and a normal vascular pattern. Pseudopapilledema sometimes occurs in hyperopic individuals. Workup of the patient with papillitis includes lumbar puncture and cerebrospinal fluid analysis. B henselae infection can be detected by serology. MRI is the preferred imaging study. An abnormal MRI is associated with a worse visual outcome.[3] ## References[edit] 1. ^ "papillitis". Millodot: Dictionary of Optometry and Visual Science, 7th edition. Butterworth-Heinemann. 2009. 2. ^ Pretest Neurology (6th ed.). p. 259. 3. ^ CURRENT Diagnosis & Treatment: Pediatrics, 21e Chapter 16. Eye > Diseases of the Optic Nerve ## External links[edit] Classification D * ICD-10: H46 * ICD-9-CM: 377.31 * DiseasesDB: 9579 This article about the eye is a stub. You can help Wikipedia by expanding it. * v * t * e * v * t * e * Diseases of the human eye Adnexa Eyelid Inflammation * Stye * Chalazion * Blepharitis * Entropion * Ectropion * Lagophthalmos * Blepharochalasis * Ptosis * Blepharophimosis * Xanthelasma * Ankyloblepharon Eyelash * Trichiasis * Madarosis Lacrimal apparatus * Dacryoadenitis * Epiphora * Dacryocystitis * Xerophthalmia Orbit * Exophthalmos * Enophthalmos * Orbital cellulitis * Orbital lymphoma * Periorbital cellulitis Conjunctiva * Conjunctivitis * allergic * Pterygium * Pseudopterygium * Pinguecula * Subconjunctival hemorrhage Globe Fibrous tunic Sclera * Scleritis * Episcleritis Cornea * Keratitis * herpetic * acanthamoebic * fungal * Exposure * Photokeratitis * Corneal ulcer * Thygeson's superficial punctate keratopathy * Corneal dystrophy * Fuchs' * Meesmann * Corneal ectasia * Keratoconus * Pellucid marginal degeneration * Keratoglobus * Terrien's marginal degeneration * Post-LASIK ectasia * Keratoconjunctivitis * sicca * Corneal opacity * Corneal neovascularization * Kayser–Fleischer ring * Haab's striae * Arcus senilis * Band keratopathy Vascular tunic * Iris * Ciliary body * Uveitis * Intermediate uveitis * Hyphema * Rubeosis iridis * Persistent pupillary membrane * Iridodialysis * Synechia Choroid * Choroideremia * Choroiditis * Chorioretinitis Lens * Cataract * Congenital cataract * Childhood cataract * Aphakia * Ectopia lentis Retina * Retinitis * Chorioretinitis * Cytomegalovirus retinitis * Retinal detachment * Retinoschisis * Ocular ischemic syndrome / Central retinal vein occlusion * Central retinal artery occlusion * Branch retinal artery occlusion * Retinopathy * diabetic * hypertensive * Purtscher's * of prematurity * Bietti's crystalline dystrophy * Coats' disease * Sickle cell * Macular degeneration * Retinitis pigmentosa * Retinal haemorrhage * Central serous retinopathy * Macular edema * Epiretinal membrane (Macular pucker) * Vitelliform macular dystrophy * Leber's congenital amaurosis * Birdshot chorioretinopathy Other * Glaucoma / Ocular hypertension / Primary juvenile glaucoma * Floater * Leber's hereditary optic neuropathy * Red eye * Globe rupture * Keratomycosis * Phthisis bulbi * Persistent fetal vasculature / Persistent hyperplastic primary vitreous * Persistent tunica vasculosa lentis * Familial exudative vitreoretinopathy Pathways Optic nerve Optic disc * Optic neuritis * optic papillitis * Papilledema * Foster Kennedy syndrome * Optic atrophy * Optic disc drusen Optic neuropathy * Ischemic * anterior (AION) * posterior (PION) * Kjer's * Leber's hereditary * Toxic and nutritional Strabismus Extraocular muscles Binocular vision Accommodation Paralytic strabismus * Ophthalmoparesis * Chronic progressive external ophthalmoplegia * Kearns–Sayre syndrome palsies * Oculomotor (III) * Fourth-nerve (IV) * Sixth-nerve (VI) Other strabismus * Esotropia / Exotropia * Hypertropia * Heterophoria * Esophoria * Exophoria * Cyclotropia * Brown's syndrome * Duane syndrome Other binocular * Conjugate gaze palsy * Convergence insufficiency * Internuclear ophthalmoplegia * One and a half syndrome Refraction * Refractive error * Hyperopia * Myopia * Astigmatism * Anisometropia / Aniseikonia * Presbyopia Vision disorders Blindness * Amblyopia * Leber's congenital amaurosis * Diplopia * Scotoma * Color blindness * Achromatopsia * Dichromacy * Monochromacy * Nyctalopia * Oguchi disease * Blindness / Vision loss / Visual impairment Anopsia * Hemianopsia * binasal * bitemporal * homonymous * Quadrantanopia subjective * Asthenopia * Hemeralopia * Photophobia * Scintillating scotoma Pupil * Anisocoria * Argyll Robertson pupil * Marcus Gunn pupil * Adie syndrome * Miosis * Mydriasis * Cycloplegia * Parinaud's syndrome Other * Nystagmus * Childhood blindness Infections * Trachoma * Onchocerciasis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Optic papillitis	c0030353	27,039	wikipedia	https://en.wikipedia.org/wiki/Optic_papillitis	2021-01-18T18:54:13	{"mesh": ["D010211"], "umls": ["C0155288", "C0919308", "C0242420", "C0030353"], "wikidata": ["Q7098800"]}
## Summary ### Clinical characteristics. Poikiloderma with neutropenia (PN) is characterized by an inflammatory eczematous rash (ages 6-12 months) followed by post-inflammatory poikiloderma (age >2 years) and chronic noncyclic neutropenia typically associated with recurrent sinopulmonary infections in the first two years of life and (often) bronchiectasis. There is increased risk for myelodysplastic syndrome and, rarely, acute myelogenous leukemia. Other ectodermal findings include nail dystrophy and palmar/plantar hyperkeratosis. Most affected individuals also have reactive airway disease and some have short stature, hypogonadotropic hypogonadism, midfacial retrusion, calcinosis cutis, and non-healing skin ulcers. ### Diagnosis/testing. Often the diagnosis of PN can be established in a proband based on clinical findings (post-inflammatory poikiloderma and congenital chronic neutropenia). Unequivocal confirmation of the diagnosis of PN relies on detection of biallelic USB1 pathogenic variants on molecular genetic testing. ### Management. Treatment of manifestations: Dermatologic manifestations are treated with gentle skin care using bland emollients and diligent sun protection; very pruritic palmar/plantar hyperkeratosis can be treated with a strong topical steroid or a topical keratolytic if secondary dermatophyte infection has been ruled out. Although use of granulocyte-colony stimulating factor (G-CSF) increases the absolute neutrophil count, there is little evidence of its clinical effect (such as decreased frequency of infections). Myelodysplastic syndrome and acute myelogenous leukemia are treated in the usual manner. Sinopulmonary, middle ear, and skin infections require aggressive treatment with antibiotics. Reactive airway disease and hypogonadotropic hypogonadism are treated in the usual manner. Prevention of secondary complications: Annual influenza vaccine; dental cleaning and evaluation for gingivitis/caries every three to six months; liberal use of sunscreens with both UVA and UVB protection to reduce the risk of skin cancer. Surveillance: Annual evaluation: * By a physician familiar with PN of CBC with differential and platelet count (for evidence of anemia and/or thrombocytopenia ‒ signs of possible myelodysplastic syndrome); * By a pulmonologist for those with bronchiectasis, chronic cough, and/or reactive airway disease; * By a dermatologist (starting at age 10 years) for skin cancer screening. In children: routine monitoring of growth, developmental milestones, school progress, and pubertal development. Agents/circumstances to avoid: Excessive sun exposure (to decrease risk of skin cancer); exposure to second-hand cigarette or wood smoke and persons with respiratory illnesses (to decrease the risk of respiratory infections). Evaluation of relatives at risk: It is appropriate to evaluate apparently asymptomatic older and younger sibs of a proband in order to identify as early as possible those who would benefit from prompt initiation of treatment and surveillance for potential complications. ### Genetic counseling. PN is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the USB1 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal and preimplantation genetic testing are possible. ## Diagnosis ### Suggestive Findings Poikiloderma with neutropenia (PN) should be suspected in individuals with the following clinical findings and laboratory findings. #### Clinical Skin * Between ages six and 12 months, inflammatory eczematous rash appearing first on the limbs and progressing to the trunk, face, and on occasion the pinnae * After age two years, post-inflammatory poikiloderma (areas of hyper- and hypopigmentation, atrophy, and telangiectasias) (Figure 1). Note: The telangiectasia may be subclinical and seen only on skin biopsy (which is not necessary for diagnosis). #### Figure 1. Post-inflammatory poikiloderma in a boy age ten years; note hypo- and hyperpigmentation. Recurrent infections (as evidence of neutropenia) * In the first two years of life, recurrent sinopulmonary infections ‒ often complicated by bronchiectasis * Adolescent- and adult-onset non-healing skin ulcers #### Laboratory Congenital chronic noncyclic neutropenia that is moderate to severe: * Moderate neutropenia: absolute neutrophil count (ANC)* 500-1000/µL * Severe neutropenia: ANC <500/ µL * ANC = white blood cell count (WBC) x % neutrophils ### Establishing the Diagnosis In many instances, the diagnosis of poikiloderma with neutropenia (PN) is established clinically in a proband with post-inflammatory poikiloderma and congenital chronic neutropenia. Unequivocal confirmation of the diagnosis of PN in individuals with a suspected clinical diagnosis or findings consistent with PN relies on molecular genetic testing demonstrating biallelic USB1 pathogenic variants (Table 1) [Colombo et al 2012, Piard et al 2012, Larizza et al 2013]. Molecular genetic testing approaches depend on the phenotype and can include a combination of gene-targeted testing (single-gene testing or a multigene panel) and genomic testing (exome or genome sequencing). Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Persons with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing, whereas those in whom a specific diagnosis has been elusive are more likely to be diagnosed using genomic testing. Gene-targeted testing * Single-gene testing. Sequence analysis of USB1 (formerly C16orf57) is performed first. To date sequence analysis has detected biallelic pathogenic variants in all tested individuals with a clinical diagnosis of poikiloderma with neutropenia. To date, no USB1 exon or whole-gene deletions have been reported. * A multigene panel that includes USB1 and other genes of interest (see Differential Diagnosis) may also be considered. 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; thus, clinicians need to determine which multigene panel provides the best opportunity to identify the genetic cause of the condition at the most reasonable cost while limiting identification of pathogenic variants in genes that do not explain the underlying phenotype. Of note, given the rarity of poikiloderma with neutropenia many custom panels for pigmentary skin disorders and neutropenia may not include USB1. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. Genomic testing * Comprehensive genomic testing includes exome sequencing and genome sequencing. 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 Poikiloderma with Neutropenia View in own window Gene 1MethodProportion of Probands with Pathogenic Variants 2 Detectable by Method USB1Sequence analysis 3All probands reported to date 4 Gene-targeted deletion/duplication analysis 5Unknown 6 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on allelic variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. Arnold et al [2010], Tanaka et al [2010], Volpi et al [2010], Walne et al [2010], Clericuzio et al [2011], Colombo et al [2012], Piard et al [2012], Farruggia et al [2014], Koparir et al [2014], Patiroglu & Akar [2015], Kilic & Cekic [2016], Suter et al [2016], Walne et al [2016], Aglaguel et al [2017] 5\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 6\. To date, no USB1 exon or whole-gene deletions have been reported. ## Clinical Characteristics ### Clinical Description Poikiloderma with neutropenia (PN) is characterized by post-inflammatory poikiloderma and chronic noncyclic neutropenia typically associated with recurrent sinopulmonary infections and (often) bronchiectasis. There is increased risk for myelodysplastic syndrome and, rarely, acute myelogenous leukemia. Other ectodermal findings include nail dystrophy (typically, thickened nails) and palmar/plantar hyperkeratosis. Most affected individuals also have reactive airway disease and some have short stature, hypogonadotropic hypogonadism, midfacial retrusion, calcinosis cutis, and non-healing skin ulcers [Colombo et al 2012]. Intrafamilial clinical variability of findings of midfacial hypoplasia, poikiloderma, and neutropenia [Concolino et al 2010] and pulmonary involvement [Patiroglu & Akar 2015] has been observed ‒ the most significant instance being acute myelogenous leukemia observed in one of two sibs [Porter et al 1999]. The clinical information that follows is based on more than 70 individuals (published and unpublished to date) with a clinical diagnosis of PN. #### Ectodermal Features Skin. The skin is normal at birth. At age six to 12 months, a nonpruritic acral eczematous-like rash develops which progresses to the trunk and face. Over the next year or so the inflammatory rash resolves, the skin becomes dry, and poikiloderma becomes evident as areas of hyper- and hypopigmentation, atrophy, and telangiectasias (Figure 1). Poikiloderma persists throughout life and may be more noticeable in individuals who have constitutionally darker skin. Palmar/plantar hyperkeratosis is common. Calcinosis cutis – small nodules that may be localized to the elbows, knees, and pinnae or more diffuse – may develop in childhood [Chantorn & Shwayder 2012]. Children and adults are prone to cellulitis (a manifestation of neutropenia) that may progress to non-healing skin ulcers. Photosensitivity has been reported in some. Squamous cell carcinoma of the skin was reported in two individuals: one age 14 years [Rodgers et al 2013] and the other "at a young age" [Walne et al 2010]. Nails. Thickened, hyperkeratotic toenails are common; dystrophic nails which can slough may also be seen (Figure 2). #### Figure 2 A. Nail dystrophy in a girl age five years B. Dysplastic toenails and squamous cell carcinoma (blue arrow) in a girl age 14 years Hair. Eyebrows and eyelashes can be sparse; hair can be dry and thin. Teeth. Delayed dental eruption and abscesses have been observed. Gingivitis and dental caries leading to tooth loss are common. #### Hematologic Findings Neutropenia. Neutropenia is usually identified in early infancy associated with recurrent sinopulmonary infections, often complicated by bronchiectasis. Most individuals with PN who are not acutely ill have moderate neutropenia; although some have severe neutropenia [Van Hove et al 2005, Farruggia et al 2014]. While the absolute neutrophil count (ANC) may rise to the low-normal range during acute infection, it is always inappropriately low and with resolution of the infection reverts to baseline neutropenia. Transient thrombocytopenia and variable anemia have been reported [Van Hove et al 2005, Walne et al 2010, Clericuzio et al 2011, Farruggia et al 2014]. #### Myelodysplasia and Hematologic Malignancies Of 26 persons with PN without a known malignancy, bone marrow studies showed: * 24 with premyelodysplastic changes (often defined as <10% abnormal cells) including increased number of immature cells and myeloid maturation defects [Van Hove et al 2005, Mostefai et al 2008, Concolino et al 2010, Tanaka et al 2010, Walne et al 2010, Clericuzio et al 2011, Farruggia et al 2014, Patiroglu & Akar 2015, Walne et al 2016]; * Two with a normal pattern. In five additional persons with PN: * Three had myelodysplastic syndrome [Pianigiani et al 2001, Colombo et al 2012, Walne et al 2016]; * Two had acute myelogenous leukemia [Porter et al 1999, Walne et al 2010]. #### Infection Almost 90% of individuals with PN have recurrent pulmonary infections including bronchiectasis, lung abscesses, and lung granulomas. Chronic recurrent otitis media and sinusitis are common in childhood. After age five to ten years, the frequency of acute sinopulmonary infections decreases, but most individuals continue to have bronchiectasis, chronic non-productive cough, and reactive airway disease. Quantitative immunoglobulins and lymphocyte subset panels are normal. #### Facial Features Facial features are normal at birth; however, over time characteristic craniofacial features of prominent forehead, depressed nasal bridge, and midface retrusion usually develop (Figure 3) [Concolino et al 2010, Colombo et al 2012, Koparir et al 2014]. #### Figure 3. Three Italian sibs with typical midfacial hypoplasia #### Other Findings Common. Birth length and weight are usually normal; however, intrauterine growth restriction (IUGR) can be seen. Postnatal-onset short stature not associated with growth hormone deficiency is common. One individual was reported to be unresponsive to growth hormone therapy [Koparir et al 2014]. Virtually all individuals have elevated serum lactate dehydrogenase of unknown etiology; some have nonspecific mild elevation of aminotransferases, aspartate aminotransferase, ferritin, and creatine phosphokinase. Hypogonadotropic hypogonadism causing delayed puberty is common. Both osteopenia and increased bone density have been reported [Migliaccio et al 1999, Porter et al 1999, Wang et al 2003, Walne et al 2010, Colombo et al 2012, Koparir et al 2014]. Associated features include increased bone fragility and osteoporosis. Two individuals who are older than age 30 years have been followed long term for poorly healing long bone fractures [Volpi et al 2010, Colombo et al 2012]. Although early developmental delays (possibly related to chronic illness) have been reported, intellectual disability has not been reported. Several patients with muscle weakness had normal muscle biopsies. Rare * Epiphora due to lacrimal duct obstruction and vocal cord nodules with hyperkeratinization, resulting in high-pitched voice [Koparir et al 2014] * Macrocephaly and microcephaly * Hepatosplenomegaly * Hypermobile fingers with "swan neck deformity" ### Genotype-Phenotype Correlations Genotype-phenotype correlations have not been established to date. ### Nomenclature Poikiloderma with neutropenia was termed "immune-deficient poikiloderma" in the publication by Clericuzio et al [1991], who first described the condition in the Navajo population. When it was subsequently reported in non-Navajo individuals, the condition was renamed poikiloderma with neutropenia [Wang et al 2003]. In 2005 Van Hove proposed renaming the disorder Clericuzio-type poikiloderma with neutropenia [Van Hove et al 2005]. ### Prevalence First described in the Navajo native American population [Clericuzio et al 1991], poikiloderma with neutropenia has since been identified in non-Navajos worldwide, including a substantial number of individuals of Turkish ancestry. ## Differential Diagnosis Table 2 summarizes inherited disorders with either poikiloderma or neutropenia in the differential diagnosis of poikiloderma with neutropenia (PN). While there is clinical overlap between PN and dyskeratosis congenita (DC) and Rothmund-Thomson syndrome (RTS), PN is clinically distinguishable from these two disorders (Table 2). Of note, several individuals who were clinically misdiagnosed as either DC or RTS in the past have been correctly diagnosed as having PN following identification of biallelic USB1 variants on molecular genetic testing [Volpi et al 2010, Walne et al 2010, Walne et al 2016]. ### Table 2. Disorders to Consider in the Differential Diagnosis of Poikiloderma with Neutropenia View in own window DisorderGene(s)MOIFeatures Overlapping with PNDistinguishing In this disorderIn PN Dyskeratosis congenitaACD CTC1 DKC1 NHP2 NOP10 PARN RTEL1 TERC TERT TINF2 WRAP53XL AD AR * Poikiloderma * Nail dystrophy * Myelodysplasia * AML * Poikiloderma upper chest/neck * Oral leukoplakia * Pulmonary fibrosis * Short telomeres (on lab testing) * Generalized (extremities & central body) post-inflammatory poikiloderma in infancy/early childhood * Nail dystrophy * Congenital chronic moderate neutropenia * Recurrent upper-respiratory infections Rothmund-Thomson syndromeRECQL4AR * Early-onset poikiloderma at extremities * Palmar/plantar hyperkeratosis * Nail dystrophy * Sparse hair & eyebrows/lashes * Dental abnormalities * Short stature * SCC skin * Early-onset facial poikiloderma * Skeletal defects (incl radial ray defects) * Gastrointestinal disturbance * Osteosarcoma Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP)FAM111BAD * Short stature * Sparse/absent eyelashes and/or eyebrows * Poikiloderma * Nail dysplasia * Palmar/plantar hyperkeratosis * Recurrent bronchitis * Thrombocytopenia, marrow hypocellularity * Poikiloderma localized to face * Hypohidrosis * Muscle contractures * Lymphedema of the extremities * Myopathy * Exocrine pancreatic insufficiency * Pulmonary fibrosis ELANE-related neutropeniaELANEAD * Congenital neutropenia * Cyclic neutropenia * Severe neutropenia * Absence of poikiloderma AD = autosomal dominant; AML = acute myelogenous leukemia; AR = autosomal recessive; MOI = mode of inheritance; SCC = squamous cell carcinoma; XL = X-linked ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with poikiloderma with neutropenia, the following evaluations are recommended: * Dermatologic evaluation to confirm poikiloderma, assess calcinosis cutis and palmar/plantar hyperkeratosis, and screen for skin cancer * Baseline complete blood count with differential and platelet count, if not done at the time of diagnosis * Hematology/oncology consultation to evaluate need for bone marrow examination (e.g., if more than one cell line is involved) * Baseline pulmonary evaluation to include evaluation for bronchiectasis and granulomas and to manage reactive airway disease * Otolaryngology evaluation to evaluate complications of chronic otitis media * For children, pediatric endocrinology evaluation to assess growth and pubertal development * Gastrointestinal evaluation if hepatosplenomegaly and/or elevated liver transaminases are present * Dental evaluation for evidence of gingivitis and/or caries * Consideration of dual-energy x-ray absorptiometry (DXA) to evaluate for low bone density in adults * Developmental evaluation for children younger than age five years * Consultation with a clinical geneticist familiar with poikiloderma with neutropenia ### Treatment of Manifestations Palmar/plantar hyperkeratosis if very pruritic ‒ and if there is no evidence of secondary dermatophyte infection ‒ can be treated for short periods with a strong topical steroid such as fluocinonide or clobetasol ointment two or three times a day. Other possible treatments include a topical keratolytic such as 40% urea, compounded salicylic acid mixed in cream, or propylene glycol. Sinopulmonary, middle ear, and skin infections should be treated aggressively with antibiotics until clinical resolution and normalization of inflammatory markers. For individuals with recurrent sinopulmonary infections, use of prophylactic antibiotics during the winter may decrease frequency of infections [Author, personal observation]. There is no rationale for immunoglobulin therapy in the absence of low immunoglobulin levels. Neutropenia. Although administration of granulocyte-colony stimulating factor (G-CSF) to patients with PN increases the absolute neutrophil count (ANC), no reports to date have indicated definitive benefit [Migliaccio et al 1999, Van Hove et al 2005, Colombo et al 2012, Rodgers et al 2013]. Based on lack of evidence of definitive benefit, G-CSF use may be considered only in patients with severe infections associated to very low neutrophil count. Bone marrow abnormalities (e.g., premyelodysplastic changes) should be followed and managed by the consulting hematologist/oncologist. Management of myelodysplastic syndrome and acute myelogenous leukemia is per routine. Delayed puberty caused by hypogonadotropic hypogonadism should be managed by an endocrinologist specialized in this condition and may include hormone replacement therapy. Growth. There is no evidence that growth hormone therapy increases linear growth. ### Prevention of Secondary Complications The following are appropriate: * Annual influenza vaccine as per standard of care * Dental cleaning and evaluation for gingivitis/caries every 3-6 months * Use of sunscreens with both UVA and UVB protection to reduce the risk of skin cancer ### Surveillance The following are appropriate: * Annual evaluation * By a physician familiar with poikiloderma with neutropenia * Of CBC with differential and platelet count for evidence of anemia and/or thrombocytopenia (signs of possible myelodysplastic syndrome) which would prompt a referral to a hematologist/oncologist for consideration of bone marrow examination * By a pulmonologist for patients with bronchiectasis, chronic cough, and/or reactive airway disease * By a dermatologist (starting at age 10 years) for skin cancer screening * Routine monitoring in children. Growth, developmental milestones, school progress, and pubertal development ### Agents/Circumstances to Avoid Avoid the following: * Excessive sun exposure (to decrease the risk for skin cancer) * Exposure to second-hand cigarette or wood smoke and persons with respiratory illnesses (to decrease the risk of respiratory infections) ### Evaluation of Relatives at Risk It is appropriate to evaluate apparently asymptomatic older and younger sibs of a proband in order to identify as early as possible those who would benefit from prompt initiation of treatment and surveillance for potential complications. Evaluations can include: * Molecular genetic testing if the USB1 pathogenic variants in the family are known; * The following if the pathogenic variants in the family are not known: * Examination by a clinician familiar with poikiloderma with neutropenia to evaluate for the characteristic skin changes * CBC with differential and platelet count especially in newborn sibs who have not manifested a skin rash 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Poikiloderma with Neutropenia	c1858723	27,040	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK459118/	2021-01-18T21:03:37	{"mesh": ["C565820"], "synonyms": ["Clericuzio-Type Poikiloderma with Neutropenia"]}
Acropustulosis SpecialtyDermatology Acropustulosis refers to acrodermatitis with pustular involvement. Types include: * Pustulosis palmaris et plantaris * Infantile acropustulosis ## References[edit] ## External links[edit] Classification D * ICD-10: L40.2 (ILDS L40.200) * v * t * e Papulosquamous disorders Psoriasis Pustular * Generalized pustular psoriasis (Impetigo herpetiformis) * Acropustulosis/Pustulosis palmaris et plantaris (Pustular bacterid) * Annular pustular psoriasis * Localized pustular psoriasis Other * Guttate psoriasis * Psoriatic arthritis * Psoriatic erythroderma * Drug-induced psoriasis * Inverse psoriasis * Napkin psoriasis * Seborrheic-like psoriasis Parapsoriasis * Pityriasis lichenoides (Pityriasis lichenoides et varioliformis acuta, Pityriasis lichenoides chronica) * Lymphomatoid papulosis * Small plaque parapsoriasis (Digitate dermatosis, Xanthoerythrodermia perstans) * Large plaque parapsoriasis (Retiform parapsoriasis) Other pityriasis * Pityriasis rosea * Pityriasis rubra pilaris * Pityriasis rotunda * Pityriasis amiantacea Other lichenoid Lichen planus * configuration * Annular * Linear * morphology * Hypertrophic * Atrophic * Bullous * Ulcerative * Actinic * Pigmented * site * Mucosal * Nails * Peno-ginival * Vulvovaginal * overlap synromes * with lichen sclerosus * with lupus erythematosis * other: * Hepatitis-associated lichen planus * Lichen planus pemphigoides Other * Lichen nitidus * Lichen striatus * Lichen ruber moniliformis * Gianotti–Crosti syndrome * Erythema dyschromicum perstans * Idiopathic eruptive macular pigmentation * Keratosis lichenoides chronica * Kraurosis vulvae * Lichen sclerosus * Lichenoid dermatitis * Lichenoid reaction of graft-versus-host disease This dermatology article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Acropustulosis	c0030246	27,041	wikipedia	https://en.wikipedia.org/wiki/Acropustulosis	2021-01-18T19:08:32	{"mesh": ["D011565"], "umls": ["C0030246"], "orphanet": ["163927"], "wikidata": ["Q4676432"]}
## Summary ### Clinical characteristics. Rhabdoid tumor predisposition syndrome (RTPS) is characterized by a markedly increased risk of developing rhabdoid tumors – rare and highly aggressive malignant tumors occurring predominantly in infants and children younger than age three years. Rhabdoid tumors can occur in almost any anatomic location, commonly in the central nervous system (i.e., atypical teratoid/rhabdoid tumor [AT/RT]); more than 50% occur in the cerebellum. Other common locations include extracranial extrarenal malignant rhabdoid tumors (e.g., rhabdoid tumors of the head and neck, paravertebral muscles, liver, bladder, mediastinum, retroperitoneum, pelvis, and heart) (eMRT), rhabdoid tumor of the kidney (RTK), and possibly small-cell carcinoma of the ovary (hypercalcemic type). Individuals with RTPS typically present before age 12 months with synchronous tumors that exhibit aggressive clinical behavior. ### Diagnosis/testing. The diagnosis of RTPS is established in a proband with a rhabdoid tumor and/or a family history of rhabdoid tumor and/or multiple SMARCA4- or SMARCB1-deficient tumors (synchronous or metachronous) and identification of a germline heterozygous pathogenic variant in SMARCA4 or SMARCB1 by molecular genetic testing. ### Management. Treatment of manifestations: Due to the rarity of RTPS, standards for management are evolving. Most individuals are treated by intensive multimodal therapeutic strategies, according to institutional preference combining surgery, radiotherapy, and chemotherapy. Prevention of primary manifestations: Prophylactic bilateral oophorectomy may be discussed after childbearing. Prevention of secondary manifestations: Consider risk-reducing treatment strategies (e.g., postpone or replace radiotherapy with high-dose chemotherapy or proton beam therapy; targeted therapy used concomitantly with, or before, standard chemotherapy). Surveillance: From birth to age one year: * Monthly physical and neurologic examination, head ultrasound, and abdominal and pelvic ultrasound recommended. * If not feasible for patients with AT/RT, monthly head ultrasound plus abdominal and pelvic ultrasound every two to three months is a minimum requirement. If fontanelle closes prematurely consider head MRI every two to three months. * For patients with eMRT, RTK: monthly head, abdominal, and pelvic ultrasound examination. * If ultrasound is not sufficient consider MRI at least every two to three months for affected site and ultrasound for all other sites. Whole-body MRI is desirable but not universally available. From age one year to age four to five years: * For patients with AT/RT: brain and total spine MRI every three months * If available, consider whole-body MRI. (Note: Whole-body MRI resolution may not be sufficent for brain MRI, which would then need to be performed separately). * For patients with eMRT, RTK: abdominal and pelvic ultrasound or MRI (or whole-body MRI) every three months. After age four years: * Twice-yearly physical examination in a tumor predisposition clinic with targeted imaging for symptomatic areas. * For patients with SMARCA4-related SCCOHT: abdominal and pelvic ultrasound every six months. 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 prompt initiation of screening, treatment, and preventive measures. ### Genetic counseling. RTPS is inherited in an autosomal dominant manner. The vast majority of individuals diagnosed with RTPS have the disorder as the result of a de novo germline SMARCB1 pathogenic variant. Most reported individuals diagnosed with SMARCA4-related RTPS inherited a pathogenic variant from an unaffected parent. Each child of an individual with a germline SMARCA4 or SMARCB1 pathogenic variant has a 50% chance of inheriting the pathogenic variant. However, penetrance appears to be incomplete and the types of RTPS-related tumors can vary among different members of the same family. Prenatal testing and preimplantation genetic testing are possible if the pathogenic variant in the family is known. ## Diagnosis ### Suggestive Findings Rhabdoid tumor predisposition syndrome (RTPS) should be suspected in an individual with any of the following clinical or laboratory features. Clinical features. Any rhabdoid tumor with the following features is particularly suspicious: * Congenital presentation (i.e., prenatal diagnosis or symptoms within the first 28 days of life) * Early-onset rhabdoid tumor (age <12 months) * Advanced stage of rhabdoid tumor (RT) at diagnosis (e.g., >M1 by Chang classification; Stage ≥II in extracranial RT [Harisiadis & Chang 1977]) * Synchronous rhabdoid tumors (>1 primary rhabdoid tumor) * Family history of rhabdoid tumor, small-cell carcinoma of the ovary hypercalcemic type, or other malignant entities such as cribriform neuroepithelial tumor, malignant peripheral nerve sheath tumor, and non-malignant schwannoma or meningioma * Family history of RTPS Given the limited patient data available, germline molecular genetic testing for RTPS is recommended in any individual with: * A rhabdoid tumor (at any age), familial rhabdoid tumors, multifocal tumors, or congenital-onset tumors; * A SMARCB1-deficient tumor (as defined by histology, rhabdoid and non-rhabdoid) with a familial history of rhabdoid tumor OR non-specified cancer in early childhood (age <5 years); * A SMARCA4-deficient tumor (as defined by histology, rhabdoid and non-rhabdoid) with a familial history of rhabdoid tumor OR non-specified cancer in early childhood (age <5 years). Note: (1) It remains to be determined whether adult-onset rhabdoid tumors are caused by germline pathogenic variants in SMARCA4 or SMARCB1. (2) As morphologic rhabdoid features may not be present in all rhabdoid tumor biopsies because of inter- and intratumoral heterogeneity, any small blue round cell tumors in infants and young children should be evaluated for absence of nuclear SMARCA4 or SMARCB1 staining. Laboratory features on tumor tissue * Immunohistochemistry. Absence of SMARCA4 (formerly BRG-1) or SMARCB1 (formerly INI-1) staining in tumor tissue * Molecular genetic testing. Somatic SMARCA4 or SMARCB1 pathogenic variants identified in a rhabdoid tumor. Note: Fresh-frozen tumor is preferable; formalin-fixed, paraffin-embedded samples may also be suitable. ### Establishing the Diagnosis There is currently no consensus regarding formal diagnostic criteria for rhabdoid tumor predisposition syndrome (RTPS). The diagnosis of RTPS is established in a proband with both of the following: * A rhabdoid tumor and/or a family history of rhabdoid tumor and/or multiple SMARCA4- or SMARCB1-deficient tumors (synchronous or metachronous) * Identification of a germline pathogenic variant in SMARCA4 or SMARCB1 by molecular genetic testing (see Table 1). Molecular genetic testing approaches can include serial single-gene testing and use of a multigene panel. Serial single-gene testing may be considered in individuals with absence of SMARCA4 or SMARCB1 identified on tumor immunohistochemistry: * Absence of SMARCA4. Sequence analysis and gene-targeted deletion/duplication analysis of SMARCA4 may be performed first. * Absence of SMARCB1. Sequence analysis and gene-targeted deletion/duplication analysis of SMARCB1 may be performed first. A multigene panel that includes SMARCA4, SMARCB1, 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 vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel provides the best opportunity to identify the genetic cause of the condition at the most reasonable cost while limiting identification of 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. ### Table 1. Molecular Genetic Testing Used in Rhabdoid Tumor Predisposition Syndrome View in own window Gene 1Proportion of RTPS Attributed to Pathogenic Variants in GeneProportion of Pathogenic Variants 2 Detectable by Method Sequence analysis 3Gene-targeted deletion/duplication analysis 4 SMARCA4~5%-15% 54/9 individuals 6, 75/9 individuals 6, 7 SMARCB1~85%-95% 8~46% 6, 9~54% 6, 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. 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\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include multiplex ligation-dependent probe amplification (MLPA) designed to detect single-exon deletions or duplications. 5\. In individuals with RTPS confirmed by germline molecular testing, a germline SMARCA4 pathogenic variant was identified in 3/50 individuals [EU-RHAB ‒ Author, personal communication], 6/35 individuals [Authors, personal communication], and 8/192 individuals [T Holsten, unpublished]. 6\. EU-RHAB ‒ Author, personal communication 7\. Hasselblatt et al [2014] 8\. In individuals with RTPS confirmed by germline molecular testing, a germline SMARCB1 pathogenic variant was identified in 47/50 individuals [EU-RHAB ‒ Author, personal communication], 29/35 individuals [Author, personal communication], and 184/192 individuals [Holsten et al 2017]. 9\. Bourdeaut et al [2011], Biegel et al [2014] ## Clinical Characteristics ### Clinical Description Rhabdoid tumor predisposition syndrome (RTPS) is characterized by a markedly increased risk of developing rhabdoid tumors. Rhabdoid tumors are rare and highly aggressive malignant tumors occurring predominantly in infants and children younger than age three years. The term rhabdoid is derived from the histologic resemblance of tumor cells to rhabdomyoblast. Rhabdoid tumors are characterized by heaps of cells with an eccentric nucleus and prominent nucleolus, abundant cytoplasm with eosinophilic inclusion bodies, and distinct cellular membranes. Immunohistochemically rhabdoid tumor cells are characterized by increased expression of vimentin (a nonspecific marker), epithelial membrane antigen (EMA), cytokeratins, and loss of SMARCB1 protein (a strong indicator for rhabdoid tumor). As morphologic rhabdoid features may not be present in all rhabdoid tumor biopsies because of inter- and intratumoral heterogeneity, any small blue round cell tumor in infants and young children should be evaluated for absence of nuclear SMARCB1 staining. Primary rhabdoid tumor locations include the following: * Central nervous system (atypical teratoid/rhabdoid tumor [AT/RT]; >50% are cerebellar) * Head and neck, paravertebral muscles, liver, bladder, mediastinum, retroperitoneum, pelvis, and heart (extracranial malignant rhabdoid tumor [eMRT]) * Kidney (rhabdoid tumor of the kidney [RTK]) * Ovary (small-cell carcinoma of the ovary [SCCOHT] ‒ hypercalcemic type) Rhabdoid tumors have been reported in nearly all anatomic locations [Brennan et al 2013, Sredni & Tomita 2015, Frühwald et al 2016a]. Individuals with RTPS typically present before age 12 months with synchronous tumors that exhibit aggressive clinical behavior, often in one of the following clinical settings: * Prenatally detected synchronous rhabdoid tumors * Infantile-onset or congenital rhabdoid tumor, presentingat median age of four to seven months (range: prenatally – 60 months) (compared to individuals with sporadic rhabdoid tumor: median age 13-30 months; range: age 1 day - 228 months) [Bruggers et al 2011, Geller et al 2015, Frühwald et al 2016b]. Note: A bias toward increased molecular testing in younger individuals may confound the data. * Synchronous (multiple primary) rhabdoid tumors. Individuals with RTPS have a higher incidence of multiple rhabdoid tumors [Eaton et al 2011]. 28% of patients with RTPS in the EU-RHAB Registry had synchronous tumors; eight individuals had AT/RT and eMRT, four individuals had AT/RT and RTK, and two individuals with congenital synchronous tumors had AT/RT, multiple eMRT, and RTK [Frühwald et al 2016b]. * Family history of rhabdoid tumor, cribriform neuroepithelial tumor (CRINET), and/or distinct combinations of rhabdoid tumor with one of the following: schwannoma, malignant peripheral nerve sheath tumor, meningioma, or CRINET [van den Munckhof et al 2012] * Family history of small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT) for SMARCA4-related RTPS (germline SMARCB1 pathogenic variants have not been reported in individuals with SCCOHT) [Moes-Sosnowska et al 2015, Witkowski et al 2017] * Clinically aggressive rhabdoid tumor. Tumor progression at the time of follow up was identified in 91% of individuals with RTPS. Progression occurred while on chemotherapy in 58% of individuals with RTPS [Sredni & Tomita 2015, EU-RHAB ‒ Author, personal communication]. * Rhabdoid tumor and syndromic features suggestive of 22q11.2 distal deletion syndrome (OMIM 611867) Prognosis. Individuals with RTPS potentially have a worse prognosis than those with a sporadic rhabdoid tumor; although long-term survival has been reported in some [Ammerlaan et al 2008, Modena et al 2013, Kordes et al 2014, Seeringer et al 2014b]. ### Phenotype Correlations by Gene SMARCA4. Small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT) has been reported in individuals with SMARCA4-related RTPS and has not been reported in individuals with germline SMARCB1 pathogenic variants. ### Genotype-Phenotype Correlations No genotype-phenotype correlations have been identified. ### Penetrance SMARCA4. Most individuals with SMARCA4-related RTPS have inherited the pathogenic variant from an unaffected, healthy parent. In SMARCA4-related RTPS the penetrance for rhabdoid tumor in the preceding generation of seven informative families was zero. However, in one family, two sibs with a SMARCA4 pathogenic variant were both affected [Schneppenheim et al 2010, Hasselblatt et al 2014]. SMARCB1. There are reports of reduced penetrance. Rarely a SMARCB1 pathogenic variant is inherited from an unaffected parent or a parent with late-onset or undiagnosed RTPS [Ammerlaan et al 2008]. Germline mosaicism accounts for at least half of the families with sibs affected by RTPS. ### Nomenclature Rhabdoid tumor predisposition syndrome may also be referred to as familial posterior fossa brain tumor syndrome. Current data suggest the value of subgroup determination for diagnostic and therapeutic decision making [Torchia et al 2015, Johann et al 2016]: * ATRT-TYR is characterized by infratentorial location, younger age at diagnosis (<1year), and overexpression of the genes TYR and MITF. * In the subgroup ATRT-MYC tumors are mostly supratentorial, affected individuals are older (age 4-5 years) at diagnosis, and the genes MYC, HOTAIR, and HOX are overexpressed. * The subgroup ATRT-SHH tumor location may be infratentorial or supratentorial, diagnosis is between ages two and five years, and sonic hedgehog pathway genes are overexpressed. Note: Torchia et al [2016] presented data on three subgroups that was similar to the subgroups described by Johann et al [2016]. A consensus on simplifying subgroup nomenclature is currently being sought. ### Prevalence Among newly diagnosed individuals with rhabdoid tumors, 25%-35% will have a germline pathogenic variant in SMARCB1 [Bourdeaut et al 2011, Eaton et al 2011, Hasselblatt et al 2014]. The incidence of rhabdoid tumors may be estimated according to the following data: * The age-standardized annual incidence rate is between five (extracranial rhabdoid tumors) and 8.1 per million (atypical teratoid/rhabdoid tumor) in children younger than age one year, and decreases to between 0.6 and 2.2 per million at ages one to four years [Brennan et al 2013, Frühwald et al 2016a]. * In the US, annual incidence among children younger than age 15 is 0.89 per million for AT/RT, 0.32 per million for eMRT, and 0.19 per million for RTK [Heck et al 2013]. ## Differential Diagnosis Sporadic tumors. Demonstration of loss of the SMARCA4 or SMARCB1 protein (in tumor tissue) due to inactivation or loss of one allele of SMARCB1 or SMARCA4 (tumor tissue and constitutional samples) may suggest the diagnosis of RTPS. For example, one individual with a constitutional deletion of SMARCB1 and an epithelioid sarcoma was reported by Le Loarer et al [2014]. The absence of a clinical and family history of rhabdoid tumor(s) distinguishes these individuals from those with RTPS. Several other malignant tumors with somatic pathogenic variants of SMARCA4 or SMARCB1 have not yet been associated with germline pathogenic variants in SMARCA4 or SMARCB1 (see Molecular Genetics, SMARCA4 and SMARCB1, Cancer and benign tumors). ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs of an individual diagnosed with rhabdoid tumor predisposition syndrome (RTPS), the following are recommended: * Refer individuals with RTPS who have not yet developed a rhabdoid tumor to a pediatric oncologist or tumor surveillance program. * Consider consulting a radiologist, prior to the planning of therapy, to assist in the selection and review of subsequent imaging, to evaluate the size and location of the primary tumor, and to evaluate for the presence of synchronous tumors and/or metastases (whole-body MRI). * For individuals with atypical teratoid/rhabdoid tumor (AT/RT), examine cerebrospinal fluid (CSF) and determine classification according to Chang staging [Harisiadis & Chang 1977]. * Refer for genetic counseling. ### Treatment of Manifestations Current data suggest the value of subgroup determination for diagnostic and therapeutic decision making [Torchia et al 2015, Johann et al 2016]: * ATRT-TYR is characterized by infratentorial location, younger age at diagnosis (<1year), and overexpression of the genes TYR and MITF. * In the subgroup ATRT-MYC tumors are mostly supratentorial, affected individuals are older (age 4-5 years) at diagnosis, and the genes MYC, HOTAIR, and HOX are overexpressed. * The subgroup ATRT-SHH tumor location may be infratentorial or supratentorial, diagnosis is between ages two and five years, and sonic hedgehog pathway genes are overexpressed. Note: Torchia et al [2016] presented data on three subgroups that was similar to the subgroups described by Johann et al [2016]. A consensus on simplifying subgroup nomenclature is currently being sought. Due to the rarity of RTPS, standards for management are evolving. Most individuals are treated by intensive multimodal therapeutic strategies, combining surgery, radiotherapy, and chemotherapy according to institutional preference: * The Children's Oncology Group has employed a combination of surgery, two cycles of induction chemotherapy (cisplatinum, cyclophosphamide, etoposide, vincristine, methotrexate), three cycles of high-dose chemotherapy with stem cell rescue (thiotepa, carboplatinum) as consolidation therapy, and radiotherapy according to age and stage [protocol ACNS0333 clinicaltrials.gov, Reddy et al 2016]. * The Dana Faber Consortium has tested combination therapy with surgery, radiotherapy, and chemotherapy (vincristine, dactinomycin, cyclophosphamide, cisplatinum, doxorubicin, temozolomide and intrathecal methotrexate, cytarabine, and hydrocortisone) [clinicaltrials.gov, Chi et al 2009]. * The EU-RHAB Registry recommends using combination therapy for rhabdoid tumors of any location (e.g., AT/RT, rhabdoid tumor of the kidney [RTK], extracranial malignant RT [eMRT]) including gross total resection, conventional chemotherapy (vincristine, dactinomycin, cyclophosphamide, doxorubicin, ifosfamide, carboplatinum, etoposide), intrathecal methotrexate, and permissive use of high-dose chemotherapy with stem cell rescue (carboplatinum, thiotepa) and radiotherapy (in individuals age >18 months). The feasibility of intensive multimodal regimen even in the youngest individuals including those affected by RTPS has been demonstrated [Seeringer et al 2014a, Bartelheim et al 2016]. * The Canadian Brain Tumour Consortium retrospectively evaluated children diagnosed with rhabdoid tumors between 1995 and 2007. Among 40 individuals, 22 received conventional chemotherapy and 18 received high-dose chemotherapy (HDCT) regimens; 15 received adjuvant radiation. Notably, six of 12 long-term survivors never received any radiotherapy [Lafay-Cousin et al 2012]. * Zaky et al evaluated the Head Start III experience for newly diagnosed patients with AT/RT. Between 2003 and 2009, 19 patients were treated with a combination of surgery and five courses of induction chemotherapy followed by consolidation with myeloablative chemotherapy and autologous hematopoietic progenitor cell rescue and radiotherapy according to age and stage. In five patients toxicity-related deaths occurred; ten patients died due to disease progression. The three-year overall survivial (OS) and event-free survival rates were 26±10% and 21±9%, respectively [Zaky et al 2014]. * Schrey et al summarized HDCT data by an individual pooled data analysis of 12 manuscripts and 389 publications including prospective and retrospective studies focused on the treatment of children diagnosed with AT/RT. Data of 332 patients demonstrated an improved outcome in those treated with HDCT-SCR and radiotherapy [Schrey et al 2016]. * Fischer-Valuck evaluated data of 361 children diagnosed with AT/RT between 2004 and 2012. The five-year OS rate was 29.9%, and it was significantly higher for patients with localized disease treated with multimodal therapy (surgery, chemotherapy, and radiotherapy) with a five-year OS of 46.8%. Patients younger than age three years at diagnosis showed significantly worse OS (5-year OS 27.7%) compared to older patients (5-year OS 37.5%) and were also significantly less likely to receive multimodal therapy (specifically, the radiotherapy component). The authors suggest early radiotherapy as an important factor for long-term cure [Fischer-Valuck et al 2017]. Note: RTPS most commonly affects infants; therapy presents a rather complex challenge due to the vulnerability of infants. The use of aggressive multimodal treatment on the developing nervous system and other organ systems of a young individual may profoundly affect developmental (e.g., neurodevelopmental) outcome, and entail significant short- and long-term side effects. Intensive induction chemotherapy may often achieve good responses and individuals may proceed with radiotherapy or (tandem) high-dose chemotherapy (HDCT) followed by autologous stem cell support. It remains to be determined whether a subgroup of children may be cured by surgery and chemotherapy alone, thus avoiding the potential severe side effects of radiotherapy to the developing brain. ### Prevention of Primary Manifestations Prophylactic bilateral oophorectomy may be discussed with women with SMARCA4-related RTPS after childbearing because of the high risk of developing small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT). ### Prevention of Secondary Complications The intensive multimodal treatment strategies required for clinically aggressive tumors in children with RTPS lead to a higher rate of secondary complications. Therapies and interventions which may prevent secondary complications include the following: * Consideration of risk-reducing treatment strategies (e.g., postpone or replace radiotherapy with HDCT or proton beam therapy; targeted therapy used concomitant with – or before – standard chemotherapy) * Long-term or lifelong surveillance in RTPS survivors (see Surveillance) ### Surveillance Surveillance guidelines for patients with RTPS have been provided by Teplick et al [2011] and Foulkes et al [2017]. Birth to age one year. Monthly physical and neurologic examination, head ultrasound, and abdominal and pelvic ultrasound are desirable. If not feasible, alternate guidelines for patients with: * AT/RT are physical and neurologic examination, including head ultrasound monthly plus every two to three months abdominal and pelvic ultrasound as a minimum requirement. If fontanelle closes prematurely consider head MRI every two to three months. * eMRT or RTK are abdominal and pelvic plus head ultrasound examination monthly. If ultrasound is not sufficient consider MRI at least every two to three months for affected site and ultrasound for all other sites. Whole-body MRI is desirable but not universally available. Age one year to age four to five years * AT/RT. Brain and total spine MRI examination every three months. If available whole-body MRI may be considered. Note: Whole-body MRI resolution may not be sufficent for brain MRI, which would then need to be performed separately. * eMRT or RTK. Abdominal and pelvic ultrasound examination or MRI every three months; alternatively, whole-body MRI After age four years the risk of developing a new rhabdoid tumor dramatically decreases [Eaton et al 2011]. It remains worthwhile, however, to screen individuals with RTPS for other manifestations (e.g., schwannomas, SCCOHT). A practical approach would include annual physical examination with targeted imaging for symptomatic areas (e.g., neurologic deficit, change in physical features, menstrual disturbances) and referral to a tumor predisposition clinic. Note: Individuals diagnosed with SMARCA4-related SCCOHT should be screened by abdominal and pelvic ultrasound examination every six months. ### Table 3. Surveillance Used in Individuals with Rhabdoid Tumor, Including Individuals with Rhabdoid Tumor Predisposition Syndrome View in own window DisorderOrganScreening According to Type of Germline Alteration and Age Predicted inactivating variantMissense variant SMARCB1-related RTPSBrainAge <1 yrAge 1 to 4-5 yrsNo screening / very low risk Head ultrasound monthly & abdominal, pelvic ultrasound every 1 (2-3) mosBrain, spine, & whole-body MRI every 3 mos AbdomenAge <1 yrAge 1 to 4-5 yrsNo screening / very low risk Abdominal, pelvic, & head ultrasound monthly, alternatively MRI every 2-3 mos 1Abdominal & pelvic ultrasound or MRI every 3 mos SMARCA4-related RTPSBrainInsufficient data 2 AbdomenInsufficient data Teplick et al [2011], Foulkes et al [2017] 1\. If ultrasound is not sufficient consider MRI at least every two to three months. 2\. One in ten individuals with AT/RT had a SMARCA4 missense germline pathogenic variant detected ### Agents/Circumstances to Avoid Limit exposure to DNA-damaging agents including radiation (e.g., x-ray, CT, external beam radiotherapy), tobacco, UV light, and chemotherapy to minimize the lifetime risk of developing late-onset secondary cancers. Imaging tests utilizing radioactive compounds should only be used if absolutely necessary for essential health care. ### Evaluation of Relatives at Risk If a germline pathogenic variant in SMARCA4 or SMARCB1 has been identified in an affected individual, molecular genetic testing of apparently asymptomatic older and younger sibs and other at-risk relatives is appropriate. Early detection of individuals who are heterozygous for an SMARCA4 or SMARCB1 pathogenic variant allows prompt initiation of surveillance, treatment, and preventative measures. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation The following clinical trials are currently recruiting unless indicated otherwise: * NCT02114229: Phase I/II trial of Alisertib as a Single Agent in Recurrent or Progressive Central Nervous System (CNS) Atypical Teratoid Rhabdoid Tumors (AT/RT) and Extra-CNS Malignant Rhabdoid Tumors (MRT) and in Combination Therapy in Newly Diagnosed AT/RT * NCT02601937: Phase I trial of the EZH2 Inhibitor Tazemetostat in Pediatric Subjects with Relapsed or Refractory INI1-Negative Tumors or Synovial Sarcoma * NCT02601950: Phase II trial Multicenter Study of the EZH2 Inhibitor Tazemetostat in Adult Subjects With INI1-Negative Tumors or Relapsed/Refractory Synovial Sarcoma * NCT03213665: Phase II trial Pediatric MATCH: Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (not recruiting) * NCT01747876: Phase I, Multi-center, Open-label Study of LEE011 in Patients with Malignant Rhabdoid Tumors and Neuroblastoma [Geoerger et al 2017] (not recruiting) * NCT02644460: Phase I trial, Abemaciclib in Children With DIPG or Recurrent/Refractory Solid Tumors (AflacST1501) Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Rhabdoid Tumor Predisposition Syndrome	c2985524	27,042	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK469816/	2021-01-18T21:00:08	{"synonyms": ["Rhabdoid Predisposition Syndrome", "RTPS"]}
Cushing ulcer SpecialtyGeneral surgery A Cushing ulcer, named after Harvey Cushing,[1][2] is a gastric ulcer associated with elevated intracranial pressure. It is also called von Rokitansky–Cushing syndrome.[2] Apart from the stomach, ulcers may also develop in the proximal duodenum and distal esophagus. ## Contents * 1 Causes * 2 Diagnosis * 3 Treatment * 4 See also * 5 References * 6 External links ## Causes[edit] The mechanism of development of Cushing ulcers is thought to be due to direct stimulation of vagal nuclei as a result of increased intracranial pressure. Brain tumors, traumatic head injury, and other intracranial processes including infections, can cause increased intracranial pressure and lead to overstimulation of the vagus nerve.Efferent fibers of the vagus nerve then release acetylcholine onto gastric parietal cell M3 receptors, causing insertion of hydrogen potassium ATPase vesicles into the apical plasma membrane. The end result is increased secretion of gastric acid with eventual ulceration of the gastric mucosa.[citation needed] ## Diagnosis[edit] As Cushing ulcers have a higher incidence of developing after shock, sepsis or trauma, diagnosis should include recent medical history evaluation. Both endoscopy and angiography can be used to locate the lesion or ulcer, though endoscopy is more commonly used as a first-line diagnosis procedure.[3] ## Treatment[edit] Most episodes of Cushing ulceration resolve on medical intervention, consisting primarily of rinsing the area with saline and the administration of antacids.[4] Patients should also be put on proton pump inhibitors during the course of treatment until their intracranial pressure lowers to a normal level. As it is caused due to vagal stimulation, vagotomy is considered as last treatment resort.[citation needed]. ## See also[edit] * Curling ulcer ## References[edit] 1. ^ synd/982 at Who Named It? 2. ^ a b Wijdicks, Eelco F.M. (2011-06-01). "Cushing's Ulcer: The Eponym and His Own". Neurosurgery. 68 (6): 1695–1698. doi:10.1227/neu.0b013e318212babf. ISSN 0148-396X. PMID 21346647. 3. ^ Moody, F. G.; Cheung, L. Y. (Dec 1976). "Stress ulcers: their pathogenesis, diagnosis, and treatment". The Surgical Clinics of North America. 56 (6): 1469–1478. doi:10.1016/s0039-6109(16)41099-6. ISSN 0039-6109. PMID 793064. 4. ^ Marrone, GC; Silen, W (May 1984). "Pathogenesis, diagnosis and treatment of acute gastric mucosal lesions". Clinics in Gastroenterology. 13 (2): 635–50. ISSN 0300-5089. PMID 6430609. ## External links[edit] Classification D * DiseasesDB: 3259 * 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 This article about a disease, disorder, or medical condition is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Cushing ulcer	c0267113	27,043	wikipedia	https://en.wikipedia.org/wiki/Cushing_ulcer	2021-01-18T18:43:34	{"umls": ["C0267113"], "wikidata": ["Q5196200"]}
Enteric neuropathy Gastro Intestinal system SpecialtyGastroenterology, Neurology Enteric neuropathy is a degenerative neuromuscular condition of the digestive system.[1] In simple terms the gut stops functioning, due to degradation of the nerves and muscles. The condition affects all parts of the digestive tract. There is no known cure or treatment for enteric neuropathy at this time; it is only possible to work on symptom management. The name enteric neuropathy only seems to be used for diagnosis within the UK. The most common name worldwide for this condition is Intestinal pseudoobstruction. ## Contents * 1 Symptoms and signs * 2 Diagnosis * 3 Treatment * 4 References * 5 External links ## Symptoms and signs[edit] The main symptom of enteric neuropathy is severe and constant pain. Other symptoms include nausea, vomiting, diarrhoea, constipation, bloating and abdominal abnormalities. In addition malabsorption and poor nutrition are common, as the digestive system begins to fail. Symptom management is very important and the main priority is usually to get on top of the pain. However, as most people may have been waiting for years for a diagnosis they are often already addicted to painkillers (such as tramadol and oramorph) and these have adverse effects on the primary condition.[citation needed] ## Diagnosis[edit] The diagnosis of enteric neuropathy is rather difficult, in that many symptoms present in ways that are common to many other bowel- and gut-related diseases. It is common that many people undergo many surgeries, sometimes over several years, to attempt to combat other possible diseases. The diagnosis itself is conducted by a physician based on multiple tests and is subjective rather than definitive, which for those who have enteric neuropathy will show signs of severe abnormalities in the movement of the gut. An operation to take a section of muscle for biopsy which, if it shows signs of nerve degradation, assists in the diagnosis.[citation needed] ## Treatment[edit] This section is empty. You can help by adding to it. (October 2017) ## References[edit] 1. ^ Reference, Genetics Home. "intestinal pseudo-obstruction". Genetics Home Reference. Retrieved 2017-10-04. ## External links[edit] Classification D * OMIM: 609629 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Enteric neuropathy	c0021847	27,044	wikipedia	https://en.wikipedia.org/wiki/Enteric_neuropathy	2021-01-18T18:34:06	{"mesh": ["D007418"], "wikidata": ["Q5380205"]}
Primary progressive aphasia (PPA) affects a person's ability to use language to communicate. This includes difficulty making or understanding speech (aphasia). PPA is a specific type of a more general disease called frontotemporal dementia. PPA can be classified into three distinct types which include: * Progressive non-fluent aphasia (PNFA) * Semantic dementia (SD) * Logopenic progressive aphasia (LPA) PPA is caused by a loss of tissue (atrophy) in the area of the brain that is responsible for producing language. In some cases, this loss of tissue is caused by genetic changes (mutations or pathogenic variants) in the GRN gene. In these cases, the disease is inherited in an autosomal dominant manner. Diagnosis of PPA is suspected when a doctor observes signs and symptoms such as progressive loss of language abilities. Imaging of the brain with a CT scan or MRI can confirm the diagnosis. Although there is no cure for the disease, treatment options include speech therapy and medication to manage behavioral changes. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Primary progressive aphasia	c0282513	27,045	gard	https://rarediseases.info.nih.gov/diseases/8541/primary-progressive-aphasia	2021-01-18T17:58:10	{"mesh": ["D018888"], "omim": ["607485"], "umls": ["C0282513"], "orphanet": ["95432"], "synonyms": ["Aphasia, primary progressive", "Primary progressive aphasia syndrome", "PPA"]}
Osteoblastoma Micrograph of an osteoblastoma. H&E stain. SpecialtyOncology Osteoblastoma is an uncommon osteoid tissue-forming[1] primary neoplasm of the bone. It has clinical and histologic manifestations similar to those of osteoid osteoma; therefore, some consider the two tumors to be variants of the same disease,[2] with osteoblastoma representing a giant osteoid osteoma. However, an aggressive type of osteoblastoma has been recognized, making the relationship less clear. Although similar to osteoid osteoma, it is larger (between 2 and 6 cm).[3] ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 3 Diagnosis * 4 Treatment * 5 Frequency * 6 References * 7 External links ## Signs and symptoms[edit] Patients with osteoblastoma usually present with pain of several months' duration. In contrast to the pain associated with osteoid osteoma, the pain of osteoblastoma usually is less intense, usually not worse at night, and not relieved readily with salicylates (aspirin and related compounds). If the lesion is superficial, the patient may have localized swelling and tenderness. Spinal lesions can cause painful scoliosis, although this is less common with osteoblastoma than with osteoid osteoma. In addition, lesions may mechanically interfere with the spinal cord or nerve roots, producing neurologic deficits. Pain and general weakness are common complaints.[citation needed] ## Pathophysiology[edit] The cause of osteoblastoma is unknown. Histologically, osteoblastomas are similar to osteoid osteomas, producing both osteoid and primitive woven bone amidst fibrovascular connective tissue, the difference being that osteoblastoma can grow larger than 2.0 cm in diameter while osteoid osteomas cannot. Although the tumor is usually considered benign, a controversial aggressive variant has been described in the literature, with histologic features similar to those of malignant tumors such as an osteosarcoma.[citation needed] ## Diagnosis[edit] When diagnosing osteoblastoma, the preliminary radiologic workup should consist of radiography of the site of the patient's pain. However, computed tomography (CT) is often necessary to support clinical and plain radiographic findings suggestive of osteoblastoma and to better define the margins of the lesion for potential surgery. CT scans are best used for the further characterization of the lesion with regard to the presence of a nidus and matrix mineralization. MRI aids in detection of nonspecific reactive marrow and soft tissue edema, and MRI best defines soft tissue extension, although this finding is not typical of osteoblastoma. Bone scintigraphy (bone scan) demonstrates abnormal radiotracer accumulation at the affected site, substantiating clinical suspicion, but this finding is not specific for osteoblastoma. In many patients, biopsy is necessary for confirmation.[citation needed] ## Treatment[edit] The first route of treatment in Osteoblastoma is via medical means. Although necessary, radiation therapy (or chemotherapy) is controversial in the treatment of osteoblastoma. Cases of postirradiation sarcoma have been reported after use of these modalities. However, it is possible that the original histologic diagnosis was incorrect and the initial lesion was an osteosarcoma, since histologic differentiation of these two entities can be very difficult.[citation needed] The alternative means of treatment consists of surgical therapy. The treatment goal is complete surgical excision of the lesion.[4] The type of excision depends on the location of the tumor. * For stage 1 and 2 lesions, the recommended treatment is extensive intralesional excision, using a high-speed burr. Extensive intralesional resections ideally consist of removal of gross and microscopic tumor and a margin of normal tissue. * For stage 3 lesions, wide resection is recommended because of the need to remove all tumor-bearing tissue. Wide excision is defined here as the excision of tumor and a circumferential cuff of normal tissue around the entity. This type of complete excision is usually curative for osteoblastoma. In most patients, radiographic findings are not diagnostic of osteoblastoma; therefore, further imaging is warranted. CT examination performed with the intravenous administration of contrast agent poses a risk of an allergic reaction to contrast material. The lengthy duration of an MRI examination and a history of claustrophobia in some patients are limiting the use of MRI. Although osteoblastoma demonstrates increased radiotracer accumulation, its appearance is nonspecific, and differentiating these lesions from those due to other causes involving increased radiotracer accumulation in the bone is difficult. Therefore, bone scans are useful only in conjunction with other radiologic studies and are not best used alone.[citation needed] ## Frequency[edit] In the US, osteoblastomas account for only 0.5-2% of all primary bone tumors and only 14% of benign bone tumors making it a relatively rare form of bone tumor.[citation needed] In regards to morbidity and mortality, conventional osteoblastoma is a benign lesion with little associated morbidity. However, the tumor may be painful, and spinal lesions may be associated with scoliosis and neurologic manifestations. Metastases and even death have been reported with the controversial aggressive variant, which can behave in a fashion similar to that of osteosarcoma. This variant is also more likely to recur after surgery than is conventional osteoblastoma.[citation needed] Osteoblastoma affects more males than it does females, with a ratio of 2–3:1 respectively. Osteoblastoma can occur in persons of any age, although the tumors predominantly affect the younger population (around 80% of these tumors occurs in persons under the age of 30). No racial predilection is recognized. It usually presents in the vertebral column or long bones.[5][6] Approximately 40% of all osteoblastomas are located in the spine. The tumors usually involve the posterior elements, and 17% of spinal osteoblastomas are found in the sacrum. The long tubular bones are another common site of involvement, with a lower extremity preponderance. Osteoblastoma of the long tubular bones is often diaphyseal, and fewer are located in the metaphysis. Epiphyseal involvement is extremely rare. Although other sites are rarely affected, several bones in the abdomen and extremities have been reported as sites of osteoblastoma tumors.[citation needed] ## References[edit] 1. ^ "osteoblastoma" at Dorland's Medical Dictionary 2. ^ George, Timothy; Daniel H. Kim; Kaufman, Bruce E.; Sean Lew; Narayan Yogananda; Patrick Barnes; Andy Herlich; Deletis, Vedran; Francesco Sala; Frederick Boop; Sigurd Berven; Menezes, Arnold H.; William C. Oakes; Keith Aronyk; Vaccaro, Alexander R. (2007). Surgery of the Pediatric Spine. Thieme New York. p. 312. ISBN 978-1-58890-342-6. 3. ^ Rubash, Harry E.; Callaghan, John; Rosenberg, Aaron (2007). The adult hip. Hagerstwon, MD: Lippincott Williams & Wilkins. p. 542. ISBN 978-0-7817-5092-9. 4. ^ Max Aebi; Gunzburg, Robert; Szpalski, Marek (2007). Vertebral Tumors. Hagerstwon, MD: Lippincott Williams & Wilkins. p. 172. ISBN 978-0-7817-8867-0. 5. ^ Tugcu B, Gunaldi O, Gunes M, Tanriverdi O, Bilgic B (October 2008). "Osteoblastoma of the temporal bone: a case report". Minim Invasive Neurosurg. 51 (5): 310–2. doi:10.1055/s-0028-1083816. PMID 18855299. 6. ^ Mortazavi SM, Wenger D, Asadollahi S, Shariat Torbaghan S, Unni KK, Saberi S (March 2007). "Periosteal osteoblastoma: report of a case with a rare histopathologic presentation and review of the literature". Skeletal Radiol. 36 (3): 259–64. doi:10.1007/s00256-006-0169-2. PMID 16868789. ## External links[edit] Classification D * ICD-O: 9200/0 * MeSH: D018215 * DiseasesDB: 31488 * SNOMED CT: 55333008 External resources * Orphanet: 58040 * v * t * e Tumours of bone and cartilage Diaphysis * Multiple myeloma * Epithelia * Adamantinoma * Primitive neuroectodermal tumor * Ewing family * Ewing's sarcoma Metaphysis Osteoblast * Osteoid osteoma * Osteoblastoma * Osteoma/osteosarcoma Chondroblast * Chondroma/ecchondroma/enchondroma * Enchondromatosis * Extraskeletal chondroma * Chondrosarcoma * Mesenchymal chondrosarcoma * Myxoid chondrosarcoma * Osteochondroma * Osteochondromatosis * Chondromyxoid fibroma Fibrous * Ossifying fibroma * Fibrosarcoma Epiphysis Chondroblast * Chondroblastoma Myeloid * Giant-cell tumor of bone Other Notochord * Chordoma [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Osteoblastoma	c0029417	27,046	wikipedia	https://en.wikipedia.org/wiki/Osteoblastoma	2021-01-18T18:54:20	{"mesh": ["D018215"], "umls": ["C0029417"], "orphanet": ["58040"], "wikidata": ["Q1807280"]}
## Clinical Features Abboy et al. (2008) described a brother and sister, both of whom died at less than 1 hour of age, with recurrent nonimmune hydrops fetalis of unknown etiology (see 236750). At birth, both individuals were noted to have marked edema of the entire body, slightly low set ears, small nose, mild micrognathia, small chest, camptodactyly, single transverse palmar creases, rhizomelic shortening of the upper extremities, slight ankle varus deformity bilaterally, and bilateral humeral fractures. Radiographs and autopsies on both patients showed diffuse soft tissue edema, gracile bones (with poor columnization of chondrocytes), especially in the upper extremities and ribs, and bilateral humeral fractures. Both sibs also had extreme pulmonary hypoplasia, hypoplastic adrenal glands, absence of germ cells, polyhydramnios, and normal or near normal fetal movements. Inheritance The occurrence of this condition in male and female sibs led Abboy et al. (2008) to suggest autosomal recessive inheritance. INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Anteriorly displaced ears Nose \- Upturned nose RESPIRATORY Lung \- Pulmonary hypoplasia CHEST External Features \- Small chest GENITOURINARY Internal Genitalia (Male) \- Absence of germ cells Internal Genitalia (Female) \- Absence of germ cells SKELETAL Limbs \- Short arms \- Slight ankle varus deformity \- Frog-leg positioning of the legs \- Bilateral humeral fractures \- Gracile bones MUSCLE, SOFT TISSUES \- Edema at birth ENDOCRINE FEATURES \- Hypoplastic adrenal glands PRENATAL MANIFESTATIONS \- Hydrops fetalis Movement \- Normal or near normal fetal movements Amniotic Fluid \- Polyhydramnios MISCELLANEOUS \- Based on report of 2 sibs in 2008 ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	HYDROPS FETALIS, NONIMMUNE, WITH GRACILE BONES AND DYSMORPHISM	c2751073	27,047	omim	https://www.omim.org/entry/613124	2019-09-22T15:59:34	{"mesh": ["C567731"], "omim": ["613124"]}
Malignant migrating partial seizures of infancy (MMPSI) is a severe form of epilepsy that begins very early in life. Recurrent seizures begin before the age of 6 months but commonly start within a few weeks of birth. The seizures do not respond well to treatment. Although affected individuals may develop normally at first, progression stalls and skills decline when seizures begin; as a result, affected individuals have profound developmental delay. The seizures in MMPSI are described as partial (or focal) because the seizure activity occurs in regions of the brain rather than affecting the entire brain. Seizure activity can appear in multiple locations in the brain or move (migrate) from one region to another during an episode. Depending on the region affected, seizures can involve sudden redness and warmth (flushing) of the face; drooling; short pauses in breathing (apnea); movement of the head or eyes to one side; twitches in the eyelids or tongue; chewing motions; or jerking of an arm, leg, or both on one side of the body. If seizure activity spreads to affect the entire brain, it causes a loss of consciousness, muscle stiffening, and rhythmic jerking (tonic-clonic seizure). Episodes that begin as partial seizures and spread throughout the brain are known as secondarily generalized seizures. Initially, the seizures associated with MMPSI are relatively infrequent, occurring every few weeks. Within a few months of the seizures starting, though, the frequency increases. Affected individuals can have clusters of five to 30 seizures several times a day. Each seizure typically lasts seconds to a couple of minutes, but they can be prolonged (classified as status epilepticus). In some cases, the seizure activity may be almost continuous for several days. After a year or more of persistent seizures, the episodes become less frequent. Seizures can affect growth of the brain and lead to a small head size (microcephaly). The problems with brain development can also cause profound developmental delay and intellectual impairment. Affected babies often lose the mental and motor skills they developed after birth, such as the ability to make eye contact and control their head movement. Many have weak muscle tone (hypotonia) and become "floppy." If seizures can be controlled for a short period, development may improve. Some affected children learn to reach for objects or walk. However, most children with this condition do not develop language skills. Because of the serious health problems caused by MMPSI, many affected individuals do not survive past infancy or early childhood. ## Frequency MMPSI is a rare condition. Although its prevalence is unknown, approximately 100 cases have been described in the medical literature. ## Causes The genetic cause of MMPSI is not fully known. Mutations in the KCNT1 gene have been found in several individuals with this condition and are the most common known cause of MMPSI. Mutations in other genes are also thought to be involved in the condition. The KCNT1 gene provides instructions for making a protein that forms potassium channels. Potassium channels, which transport positively charged atoms (ions) of potassium into and out of cells, play a key role in a cell's ability to generate and transmit electrical signals. Channels made with the KCNT1 protein are active in nerve cells (neurons) in the brain, where they transport potassium ions out of cells. This flow of ions is involved in generating currents to activate (excite) neurons and send signals in the brain. KCNT1 gene mutations alter the KCNT1 protein. Electrical currents generated by potassium channels made with the altered KCNT1 protein are abnormally increased, which allows unregulated excitation of neurons in the brain. Seizures develop when neurons in the brain are abnormally excited. It is unclear why seizure activity can migrate in MMPSI. Repeated seizures in affected individuals contribute to the developmental delay that is characteristic of this condition. ### Learn more about the genes associated with Malignant migrating partial seizures of infancy * KCNT1 * SCN1A * TBC1D24 ## Inheritance Pattern MMPSI is not inherited from a parent and does not run in families. This condition is caused by a new mutation that occurs very early in embryonic development (called a de novo mutation). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Malignant migrating partial seizures of infancy	c3554195	27,048	medlineplus	https://medlineplus.gov/genetics/condition/malignant-migrating-partial-seizures-of-infancy/	2021-01-27T08:25:53	{"gard": ["12919"], "omim": ["614959"], "synonyms": []}
Hypobetalipoproteinemia (HBL) constitutes a group of lipoprotein metabolism disorders that are characterized by permanently low levels (below the 5th percentile) of apolipoprotein B and LDL cholesterol. ## Epidemiology HBL affects around 1/1,000 individuals. ## Clinical description There are two types of HBL: familial hypobetalipoproteinemia and chylomicron retention disease (CMRD; see these terms). The familial form can be severe with early onset (abetalipoproteinemia/homozygous familial hypobetalipoproteinemia; see this term) or benign (benign familial hypobetalipoproteinemia; see this term). Severe familial HBL and CMRD appear in infancy or childhood. As a result they are often associated with growth delay, diarrhea with steatorrhea, and fat malabsorption. Infants with severe familial hypobetalipoproteinemia have hepatomegaly with steatosis, spastic ataxia, atypical retinitis pigmentosa, acanthocytosis, low levels of liposoluble vitamins (A, E and K), and major cytolysis and even cirrhosis. Benign familial hypobetalipoproteinemia is generally asymptomatic, but in adults is occasionally associated with dietary intolerance to fat, steatorrhea after oral intake of lipids, moderate cytolysis, cholelithiasis, moderately low levels of liposoluble vitamins and acanthocytosis. Moderate hepatic steatosis and paresthesia of the extremities are sometimes observed. ## Etiology HBL disorders are caused by mutations in proteins involved in the synthesis, secretion and catabolism of lipoproteins containing apolipoprotein B (LDL, VLDL and chylomicrons). Abetalipoproteinemia is inherited in a recessive manner and is a result of mutations of two alleles of the MTTP gene (MTP; 4q24). Other severe early familial hypobetalipoproteinemias are inherited in a codominant manner and are a result of mutations of two alleles of the APOB gene (2p24-p23). Benign familial hypobetalipoproteinemia, which is also inherited in a codominant manner, can be caused by heterozygous mutations of the APOB gene or the PCSK9 gene (1p34.1-p32). CMRD, which is inherited in an autosomal recessive manner, is caused by mutations of two alleles of the SAR1B gene (SARA2; 5q31.1). ## Diagnostic methods Diagnosis of familial hypobetalipoproteinemia is based on lipid analysis, after 12 hours of fasting, carried out on the patient and their parents to measure serum levels of LDL (<0.10g/L for the severe form; <0.80g/L for the moderate form), triglycerides (<0.20 g/L for the severe form; <0.50g/L for the moderate form), and apolipoprotein B (<0.10g/L for the severe form; <0.50g/L for the moderate form). Evaluation of steatorrhea and truncated apolipoprotein B after oral lipid intake, measurement of liposoluble vitamins (A, E, K), testing for acanthocytosis (on blood smears), complete neurological examination, hepatic ultrasound and eye examination can also be carried out. Diagnosis of CMRD is based on the absence in serum, after oral lipid intake, of intestinal apolipoprotein B (ApoB-48) and the appearance of `white intestine' seen endoscopically. ## Differential diagnosis Differential diagnoses of HBL include metabolic diseases with hepatic overload, with steatosis and/or hepatomegaly, atypical diseases of the central and peripheral nervous system, and secondary causes of hypocholesterolemia (iatrogenic or systemic). ## Antenatal diagnosis Prenatal diagnosis is feasible when the causal mutations in both parents are known. ## Management and treatment Management of the moderate forms of HBL includes reduction of the proportion of fat in the patient's diet and vitamin E supplementation. Management of the severe forms of HBL and CMRD should take place in specialized centers. ## Prognosis The prognosis of HBL is severe when the disease manifests in early childhood, and is excellent for the moderate form without cytolysis and steatosis. A familial syndrome of longevity has been observed in the benign forms of HBL (many patients live over the age of 85). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Hypobetalipoproteinemia	c0020597	27,049	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=31154	2021-01-23T17:17:05	{"mesh": ["D006995"], "umls": ["C0020597"], "icd-10": ["E78.6"]}
Carotid artery stenosis Other namesTIA - carotid artery[1] Carotid Artery Disease SpecialtyVascular surgery Carotid artery stenosis is a narrowing or constriction of any part of the carotid arteries, usually caused by atherosclerosis. ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 3 Diagnosis * 4 Screening * 5 Treatment * 5.1 Medication * 5.2 Revascularization * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] The common carotid artery is the large artery whose pulse can be felt on both sides of the neck under the jaw. On the right side it starts from the brachiocephalic artery (a branch of the aorta), and on the left side the artery comes directly off the aortic arch. At the throat it forks into the internal carotid artery and the external carotid artery. The internal carotid artery supplies the brain, and the external carotid artery supplies the face. This fork is a common site for atherosclerosis, an inflammatory build-up of atheromatous plaque inside the common carotid artery, or the internal carotid arteries that causes them to narrow. The plaque can be stable and asymptomatic, or it can be a source of embolization. Emboli break off from the plaque and travel through the circulation to blood vessels in the brain. As the vessels get smaller, an embolus can lodge in the vessel wall and restrict the blood flow to parts of the brain. This ischemia can either be temporary, yielding a transient ischemic attack, or permanent resulting in a thromboembolic stroke. Clinically, risk of stroke from carotid artery stenosis is evaluated by the presence or absence of symptoms and the degree of stenosis on imaging. Transient ischemic attacks (TIAs) are a warning sign, and may be followed by severe permanent strokes, particularly within the first two days. TIAs by definition last less than 24 hours and frequently take the form of a weakness or loss of sensation of a limb or the trunk on one side of the body, or the loss of sight (amaurosis fugax) in one eye. Less common symptoms are artery sounds (bruits), or ringing in the ears (tinnitus). ## Pathophysiology[edit] Atherosclerosis causes plaque to form within the carotid artery walls, usually at the fork where the common carotid artery divides into the internal and external carotid artery. The plaque build up can narrow or constrict the artery lumen, a condition called stenosis. Rupture of the plaque can cause the formation of a blood clot in the artery. A piece of the formed blood clot often breaks off and travels (embolizes) up through the internal carotid artery into the brain, where it blocks circulation, and can cause death of the brain tissue, a condition referred to as ischemic stroke. Sometimes the stenosis causes temporary symptoms first, known as TIAs, where temporary ischemia occurs in the brain, spinal cord, or retina without causing an infarction.[2] Symptomatic stenosis has a high risk of stroke within the next 2 days. National Institute for Health and Clinical Excellence (NICE) guidelines recommend that people with moderate to severe (50–99% blockage) stenosis, and symptoms, should have "urgent" endarterectomy within 2 weeks.[3] When the plaque does not cause symptoms, people are still at higher risk of stroke than the general population, but not as high as people with symptomatic stenosis. The incidence of stroke, including fatal stroke, is 1–2% per year. The surgical mortality of endarterectomy ranges from 1–2% to as much as 10%. Two large randomized clinical trials have demonstrated that carotid surgery done with a 30-day stroke and death risk of 3% or less will benefit asymptomatic people with ≥60% stenosis who are expected to live at least 5 years after surgery.[4][5] Surgeons are divided over whether asymptomatic people should be treated with medication alone or should have surgery.[6][7] The common carotid artery is the large vertical artery in red. The blood supply to the carotid artery starts at the arch of the aorta (bottom). The carotid artery divides into the internal carotid artery and the external carotid artery. The internal carotid artery supplies the brain. Plaque often builds up at that division, and causes a narrowing (stenosis). Pieces of plaque can break off and block the small arteries above in the brain, which causes a stroke. Plaque can also build up at the origin of the carotid artery at the aorta. * Carotid arteries * Section of carotid artery with plaque. Blood flows from the common carotid artery(bottom), and divides into the internal carotid artery (left) and external carotid artery (right). The atherosclerotic plaque is the dark mass on the left ## Diagnosis[edit] 70 percent stenosis of the right internal carotid artery as seen by ultrasound. Arrow marks the lumen of the artery. CT image of a 70 percent stenosis of the right internal carotid artery Carotid artery stenosis is usually diagnosed by color flow duplex ultrasound scan of the carotid arteries in the neck. This involves no radiation, no needles and no contrast agents that may cause allergic reactions. This test has good sensitivity and specificity.[8] Typically duplex ultrasound scan is the only investigation required for decision making in carotid stenosis as it is widely available and rapidly performed. However, further imaging can be required if the stenosis is not near the bifurcation of the carotid artery. One of several different imaging modalities, such as a computed tomography angiogram (CTA)[9][10][11] or magnetic resonance angiogram (MRA) may be useful. Each imaging modality has its advantages and disadvantages - Magnetic resonance angiography and CT angiography with contrast is contraindicated in patients with chronic kidney disease, catheter angiography has a 0.5% to 1.0% risk of stroke, MI, arterial injury or retroperitoneal bleeding. The investigation chosen will depend on the clinical question and the imaging expertise, experience and equipment available.[12] For purposed of treatment, the degree of carotid stenosis is defined as: percent stenosis = ( 1 − ( minimum diameter within stenosis) / ( poststenotic diameter ) ) × 100%. ## Screening[edit] The need for screening for carotid artery stenosis depends on whether someone is experiencing symptoms arising from the stenosis or has risk factors for the development of carotid artery disease. The U.S. Preventive Services Task Force (USPSTF) recommends against routine screening for carotid artery stenosis in those without symptoms.[13] While routine population screening is not advised, the American Heart Association recommends screening for people who don’t have symptoms of carotid stenosis but have been diagnosed with related medical conditions or have risk factors for carotid artery disease.[14] Screening is recommended for people who have: * Vascular disease elsewhere in the body, including: * Peripheral artery disease (PAD) * Coronary artery disease (CAD) * Atherosclerotic aortic aneurysm (AAA) * Two or more of the following risk factors: * High blood pressure (hypertension) * High cholesterol (hyperlipidemia) * Tobacco smoking * Family history – First degree relative diagnosed with atherosclerosis before age 60 or who suffered an ischemic stroke The American Heart Association also recommends screening if a physician detects a carotid bruit, or murmur, over the carotid artery by listening through a stethoscope during a physical exam. For people with symptoms, the American Heart Association recommends initial screening using ultrasound (see diagnosis below). ## Treatment[edit] The goal of treating carotid artery stenosis is to reduce the risk of stroke. The type of treatment depends on the severity of the disease and includes: * Lifestyle modifications including smoking cessation, eating a healthy diet and reducing sodium intake, losing weight, and exercising regularly. * Medications to control high blood pressure and high levels of lipids in the blood. * Surgical intervention for carotid artery revascularization. ### Medication[edit] Clinical guidelines (such as those of the American Heart Association (AHA)[15] and National Institute for Clinical Excellence (NICE)[16]) recommend that all patients with carotid stenosis be given medication, usually blood pressure lowering medications, anti-clotting medications, anti-platelet medications (such as aspirin or clopidogrel), and especially statins (which were originally prescribed for their cholesterol-lowering effects but were also found to reduce inflammation and stabilize plaque). ### Revascularization[edit] According to the American Heart Association, interventions beyond medical management is based upon whether patients have symptoms: * Asymptomatic patients: assessment of other medical conditions, life expectancy, and other individual factors; evaluation of the risks versus benefits; and patient preference are considered when determining whether surgical intervention should be performed. * Symptomatic patients: it is recommended that patients who have experienced a transient ischemic attack or non-severely disabling acute ischemic stroke undergo surgical intervention, if possible. All interventions for carotid revascularization (carotid endarterectomy, carotid stenting, and transcarotid artery revascularization) carry some risk of stroke; however, where the risk of stroke over time from medical management alone is high, intervention may be beneficial. ## See also[edit] Ocular ischemic syndrome ## References[edit] 1. ^ "Carotid artery disease: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 29 May 2019. 2. ^ Easton, J. D.; Saver, J. L.; Albers, G. W.; Alberts, M. J.; Chaturvedi, S.; Feldmann, E.; et al. (2009). "Definition and Evaluation of Transient Ischemic Attack: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease: The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists". Stroke. 40 (6): 2276–2293. doi:10.1161/STROKEAHA.108.192218. ISSN 0039-2499. PMID 19423857. 3. ^ Swain S, Turner C, Tyrrell P, Rudd A (July 2008). "Diagnosis and initial management of acute stroke and transient ischaemic attack: summary of NICE guidance". BMJ. 337: a786. doi:10.1136/bmj.a786. PMID 18653633. 4. ^ Executive Committee for the Asymptomatic Carotid Atherosclerosis Study (ACAS) (1995). "Endarterectomy for asymptomatic carotid artery stenosis". JAMA. 273 (18): 1421–1428. doi:10.1001/jama.273.18.1421. 5. ^ Halliday A, Mansfield A, Marro J, Peto C, Peto R, Potter J, Thomas D (2004). "Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial". Lancet. 363 (9420): 1491–1502. doi:10.1016/s0140-6736(04)16146-1. PMID 15135594. 6. ^ Sila CA, Higashida RT, Clagett GP (April 2008). "Clinical decisions. Management of carotid stenosis". N. Engl. J. Med. 358 (15): 1617–21. doi:10.1056/NEJMclde0800741. PMID 18403770. 7. ^ Drug Therapy Gains Favor to Avert Stroke, By THOMAS M. BURTON, Wall Street Journal, MARCH 3, 2009. Layman's summary of surgery vs. medication-only debate. 8. ^ Jahromi, AS; Cinà, CS; Liu, Y; Clase, CM (June 2005). "Sensitivity and specificity of color duplex ultrasound measurement in the estimation of internal carotid artery stenosis: a systematic review and meta-analysis". Journal of Vascular Surgery. 41 (6): 962–72. doi:10.1016/j.jvs.2005.02.044. PMID 15944595. 9. ^ Bartlett ES, Walters TD, Symons SP, Fox AJ (January 2006). "Quantification of carotid stenosis on CT angiography". AJNR. American Journal of Neuroradiology. 27 (1): 13–19. PMID 16418349. 10. ^ White JH, Bartlett ES, Bharatha A, Aviv RI, Fox AJ, Thompson AL, Bitar R, Symons SP (July 2010). "Reproducibility of semi-automated measurement of carotid stenosis on CTA". The Canadian Journal of Neurological Sciences. 37 (4): 498–503. doi:10.1017/s0317167100010532. PMID 20724259. 11. ^ Lian K, White JH, Bartlett ES, Bharatha A, Aviv RI, Fox AJ, Symons SP (May 2012). "NASCET percent stenosis semi-automated versus manual measurement on CTA". The Canadian Journal of Neurological Sciences. 39 (3): 343–6. doi:10.1017/s0317167100013482. PMID 22547515. 12. ^ Solomon, Caren G.; Grotta, James C. (19 September 2013). "Carotid Stenosis". New England Journal of Medicine. 369 (12): 1143–1150. doi:10.1056/NEJMcp1214999. PMID 24047063. 13. ^ Jonas, DE; Feltner, C; Amick, HR; Sheridan, S; Zheng, ZJ; Watford, DJ; Carter, JL; Rowe, CJ; Harris, R (Jul 8, 2014). "Screening for Asymptomatic Carotid Artery Stenosis: A Systematic Review and Meta-analysis for the U.S. Preventive Services Task Force". Annals of Internal Medicine. 161 (5): 336–46. doi:10.7326/M14-0530. PMID 25004169. 14. ^ "Guideline on the Management of Patients With Extracranial Carotid and Vertebral Artery Disease" (PDF). American Heart Association. 15. ^ http://my.americanheart.org/idc/groups/ahamah-public/@wcm/@sop/@spub/documents/downloadable/ucm_430166.pdf 16. ^ "Carotid Artery Stenosis information. Internal carotis occlusion". patient.info. Retrieved 2018-10-08. ## External links[edit] Classification D * ICD-10: I65.2 * ICD-9-CM: 433.1 * MeSH: D016893 * DiseasesDB: 31178 External resources * MedlinePlus: 007427 * v * t * e Cerebrovascular diseases including stroke Ischaemic stroke Brain * Anterior cerebral artery syndrome * Middle cerebral artery syndrome * Posterior cerebral artery syndrome * Amaurosis fugax * Moyamoya disease * Dejerine–Roussy syndrome * Watershed stroke * Lacunar stroke Brain stem * Brainstem stroke syndrome * Medulla * Medial medullary syndrome * Lateral medullary syndrome * Pons * Medial pontine syndrome / Foville's * Lateral pontine syndrome / Millard-Gubler * Midbrain * Weber's syndrome * Benedikt syndrome * Claude's syndrome Cerebellum * Cerebellar stroke syndrome Extracranial arteries * Carotid artery stenosis * precerebral * Anterior spinal artery syndrome * Vertebrobasilar insufficiency * Subclavian steal syndrome Classification * Brain ischemia * Cerebral infarction * Classification * Transient ischemic attack * Total anterior circulation infarct * Partial anterior circulation infarct Other * CADASIL * Binswanger's disease * Transient global amnesia Haemorrhagic stroke Extra-axial * Epidural * Subdural * Subarachnoid Cerebral/Intra-axial * Intraventricular Brainstem * Duret haemorrhages General * Intracranial hemorrhage Aneurysm * Intracranial aneurysm * Charcot–Bouchard aneurysm Other * Cerebral vasculitis * Cerebral venous sinus thrombosis * v * t * e Cardiovascular disease (vessels) Arteries, arterioles and capillaries Inflammation * Arteritis * Aortitis * Buerger's disease Peripheral artery disease Arteriosclerosis * Atherosclerosis * Foam cell * Fatty streak * Atheroma * Intermittent claudication * Critical limb ischemia * Monckeberg's arteriosclerosis * Arteriolosclerosis * Hyaline * Hyperplastic * Cholesterol * LDL * Oxycholesterol * Trans fat Stenosis * Carotid artery stenosis * Renal artery stenosis Other * Aortoiliac occlusive disease * Degos disease * Erythromelalgia * Fibromuscular dysplasia * Raynaud's phenomenon Aneurysm / dissection / pseudoaneurysm * torso: Aortic aneurysm * Abdominal aortic aneurysm * Thoracic aortic aneurysm * Aneurysm of sinus of Valsalva * Aortic dissection * Aortic rupture * Coronary artery aneurysm * head / neck * Intracranial aneurysm * Intracranial berry aneurysm * Carotid artery dissection * Vertebral artery dissection * Familial aortic dissection Vascular malformation * Arteriovenous fistula * Arteriovenous malformation * Telangiectasia * Hereditary hemorrhagic telangiectasia Vascular nevus * Cherry hemangioma * Halo nevus * Spider angioma Veins Inflammation * Phlebitis Venous thrombosis / Thrombophlebitis * primarily lower limb * Deep vein thrombosis * abdomen * Hepatic veno-occlusive disease * Budd–Chiari syndrome * May–Thurner syndrome * Portal vein thrombosis * Renal vein thrombosis * upper limb / torso * Mondor's disease * Paget–Schroetter disease * head * Cerebral venous sinus thrombosis * Post-thrombotic syndrome Varicose veins * Gastric varices * Portacaval anastomosis * Caput medusae * Esophageal varices * Hemorrhoid * Varicocele Other * Chronic venous insufficiency * Chronic cerebrospinal venous insufficiency * Superior vena cava syndrome * Inferior vena cava syndrome * Venous ulcer Arteries or veins * Angiopathy * Macroangiopathy * Microangiopathy * Embolism * Pulmonary embolism * Cholesterol embolism * Paradoxical embolism * Thrombosis * Vasculitis Blood pressure Hypertension * Hypertensive heart disease * Hypertensive emergency * Hypertensive nephropathy * Essential hypertension * Secondary hypertension * Renovascular hypertension * Benign hypertension * Pulmonary hypertension * Systolic hypertension * White coat hypertension Hypotension * Orthostatic hypotension [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Carotid artery stenosis	c0007282	27,050	wikipedia	https://en.wikipedia.org/wiki/Carotid_artery_stenosis	2021-01-18T19:07:06	{"mesh": ["D016893"], "umls": ["C0007282"], "icd-10": ["I65.2"], "wikidata": ["Q1576205"]}
A rare, benign, primary bone dysplasia characterized by progressive replacement of normal bone and marrow with fibrous connective tissue in either one (monostotic) or multiple (polyostotic) bones. Clinical manifestations depend on the anatomic location of the replacement and may include bone pain, deformities, pathological fractures, and cranial nerve deficits. ## Epidemiology The prevalence is unknown and is difficult to estimate due to the frequent asymptomatic lesions. ## Clinical description FD can involve the craniofacial, axial, and/or appendicular skeleton separately or simultaneously, and ranges from isolated asymptomatic monostotic lesions to severely incapacitating polyostotic lesions leading to pain, fracture, deformity or loss of vision and hearing. The monostotic form represents approximately 70% of cases, may present with pain or a pathologic fracture, and is usually diagnosed between 10 to 30 years of age. The polyostotic form represents 20-30% of cases with the majority of patients becoming symptomatic before 10 years of age. The most common sites of involvement include the femur, tibia, skull and facial bones, pelvis, rib, humerus, radius and ulna, lumbar spine, clavicle, and cervical spine. Lesions may be unilateral or, less commonly, bilateral. Initial symptoms are usually pain in the involved limb(s), associated with a limp if the lower extremity is involved, and spontaneous fracture. Weakened structural integrity frequently leads to significant bowing and leg-length discrepancies in patients with limb involvement. Sphenoidal bone involvement is variably associated with cranial nerve deficits, essentially loss of vison (affecting less than 10% of individuals with optic nerve compression). Many patients with polyostotic forms also present with renal phosphate wasting, which accounts for an increased risk of fracture. At the extreme end of the spectrum, a small proportion of patients also have endocrine manifestations, the most common being a peripheral precocious puberty. Hyperthyroidism and growth hormone hypersecretion are also quite frequently observed, while Cushing syndrome is exceptional. These patients also have café-au-lait cutaneous spots. These endocrine or cutaneous features represent the McCune-Albright syndrome. Pancreatic intraductal papillary mucinous neoplasms have been described in patients with extended forms. ## Etiology Activating somatic mutations in the GNAS gene (20q13.32), which encodes the alpha-subunit of the Gs protein receptor (Gsalpha) in target cells, is responsible for bone cell alterations as well as for the involvement of other cells/tissues bearing the same molecular defect (melanocytes, endocrine cells). ## Diagnostic methods Imaging and, when necessary, histology are the cornerstones of diagnosis. The pathognomonic radiological picture includes radiolucency and a ''ground glass'' appearance (with no visible trabecular pattern in affected areas), variable presence of endosteal scalloping of the inner cortex (but with a smooth nonreactive periosteal surface), curvature of the femoral neck and proximal shaft (often causing a coxa vara deformity of the knee), and shepherd's crook deformity. ## Differential diagnosis Differential diagnoses includes osteofibrous dysplasia, osteochondroma, exostosis, osteosarcoma, chondrosarcoma, osteofibroma, skull meningioma, osteoma ## Genetic counseling Mutations affect only somatic cells and are therefore not hereditary, thus genetic counseling may provide reassurance but is not strictly necessary. ## Management and treatment The conventional therapeutic approach is essentially symptomatic (analgesics) and orthopedic (prevention and treatment of bone complications). Treatment is typically with intravenous pamidronate, which rapidly relieves bone pain in most patients, and progressively increases bone mineralization in osteolytic areas in about half of patients. In contrast, placebo controlled randomized trials have shown that oral bisphosphonates are no more efficacious than placebo to reduce bone pain. Tubular phosphate wasting is common and should be treated with phosphate supplementation and calcitriol. ## Prognosis Prognosis is generally good in patients with the monostotic form. Polyostotic patients need to be monitored more closely, but as disease has a tendency to stabilize after adolescence, outcomes are often good in adults. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Fibrous dysplasia of bone	c0016063	27,051	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=249	2021-01-23T18:20:51	{"gard": ["6444"], "mesh": ["D005357"], "umls": ["C0016063"], "icd-10": ["Q78.1"]}
In psychology, disinhibition is a lack of restraint manifested in disregard of social conventions, impulsivity, and poor risk assessment. Disinhibition affects motor, instinctual, emotional, cognitive, and perceptual aspects with signs and symptoms similar to the diagnostic criteria for mania. Hypersexuality, hyperphagia, and aggressive outbursts are indicative of disinhibited instinctual drives.[1] ## Contents * 1 Clinical concept * 2 Treatment approaches * 2.1 Reactive * 2.2 Proactive * 3 See also * 4 References * 5 External links ## Clinical concept[edit] According to Grafman, et al.,[1] "disinhibition" is a lack of restraint manifested in several ways, affecting motor, instinctual, emotional, cognitive, and perceptual aspects with signs and symptoms, e.g., impulsivity, disregard for others and social norms, aggressive outbursts, misconduct and oppositional behaviours, disinhibited instinctual drives including risk taking behaviours and hypersexuality. Disinhibition is a common symptom following brain injury, or lesions, particularly to the frontal lobe and primarily to the orbitofrontal cortex.[2] The neuropsychiatric sequelae following brain injuries could include diffuse cognitive impairment, with more prominent deficits in the rate of information processing, attention, memory, cognitive flexibility, and problem solving. Prominent impulsivity, affective instability, and disinhibition are seen frequently, secondary to injury to frontal, temporal, and limbic areas. In association with the typical cognitive deficits, these sequelae characterise the frequently noted "personality changes" in TBI (Traumatic Brain Injury) patients. Disinhibition syndromes, in brain injuries and insults including brain tumors, strokes and epilepsy range from mildly inappropriate social behaviour, lack of control over one's behaviour to the full-blown mania, depending on the lesions to specific brain regions. Several studies in brain traumas and insults have demonstrated significant associations between disinhibition syndromes and dysfunction of orbitofrontal and basotemporal cortices, affecting visuospatial functions, somatosensation, and spatial memory, motoric, instinctive, affective, and intellectual behaviours.[2] Disinhibition syndromes have also been reported with mania-like manifestations in old age with lesions to the orbito-frontal and basotemporal cortex involving limbic and frontal connections (orbitofrontal circuit), especially in the right hemisphere.[3] Behavioural disinhibition as a result of damage to frontal lobe could be seen as a result of consumption of alcohol and central nervous system depressants drugs, e.g., benzodiazepines that disinhibit the frontal cortex from self-regulation and control.[4][5] It has also been argued that ADHD, hyperactive/impulsive subtype have a general behavioural disinhibition beyond impulsivity and many morbidities or complications of ADHD, e.g., conduct disorder, anti-social personality disorder, substance abuse, and risk taking behaviours are all consequences of untreated behavioural disinhibition.[6] ## Treatment approaches[edit] This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (June 2020) (Learn how and when to remove this template message) Positive Behaviour Support (PBS) is a treatment approach that looks at the best way to work with each individual with disabilities. A behavioural therapist conducts a functional analysis of behaviour which helps to determine ways to improve the quality of life for the person and does not just deal with problem behaviour. PBS also acknowledges the needs of support staff and includes strategies to manage crises when they arise. The following model is a brief guide to staff to remind them of key things to think about when planning support for a person with disabilities. There are two main objectives: reacting situationally when the behaviour occurs, and then acting proactively to prevent the behaviour from occurring. ### Reactive[edit] Reactive strategies include:[7] * Redirection: distracting the person by offering another activity, or changing the topic of conversation. Offer the person a choice of 2 or 3 things, but no more than 3, because this can be overwhelming. In offering a choice, make sure to pause to allow the person time to process the information and give a response. * Talking to the person and finding out what the problem is * Working out what the person's behaviour is trying to communicate * Crisis management ### Proactive[edit] Proactive strategies to prevent problems can include:[7] * Change the environment: This can include increasing opportunities for access to a variety of activities, balancing cognitively and physically demanding activities with periods of rest, providing a predictable environment in order to reduce the level of cognitive demands on the person, trying to provide consistent routines (be mindful of events that may not occur, try not to make promises that cannot be kept, if unable to go out at a particular time then say so), checking for safety in the home environment (e.g., changing/moving furniture). * Teach a skill: These can include general skills development of useful communication strategies, coping skills (e.g. teach the person what to do when feeling angry, anxious) * Individual behaviour support plans: These involve reinforcing specific desirable behavior and ignoring the specific undesirable behavior (unless it is dangerous, the priority is to keep both people safe through a crisis plan which might involve removing sharp objects or weapons, escaping to a safe place, giving the person time to calm down), avoiding things you know upsets the person, strategies to increase engagement in activities. Broadly speaking, when the behavior occurs, assertively in a nonjudgmental, clear, unambiguous way provide feedback that the behavior is inappropriate, and say what you prefer instead. For example, "Jane, you're standing too close when you are speaking to me, I feel uncomfortable, please take a step back", or "I don't like it when you say I look hot in front of your wife, I feel uncomfortable, I am your Attendant Carer/Support Worker, I am here to help you with your shopping" Also in non-verbal communication, communication can appear in other forms, one could say "I don't like it when you dart your eyes at me in that way". Then re-direct to the next activity. Any subsequent behavior ignore. Then generally, as almost all behavior is communication, understand what the behavior is trying to communicate and look at ways to have the need met in more appropriate ways. ## See also[edit] * Boldness * Frontotemporal dementia * Online disinhibition effect * Orbitofrontal cortex ## References[edit] 1. ^ a b Grafman, Jordan; François Boller; Rita Sloan Berndt; Ian H. Robertson; Giacomo Rizzolatti (2002). Handbook of Neuropsychology. Elsevier Health Sciences. p. 103. ISBN 978-0-444-50365-7. 2. ^ a b Starkstein SE, Robinson RG (1997). "Mechanism of disinhibition after brain lesions". J Nerv Ment Dis. 185 (2): 108–14. doi:10.1097/00005053-199702000-00007. PMID 9048703. 3. ^ Shulman KI (1997). "Disinhibition syndromes, secondary mania and bipolar disorder in old age". J Affect Disord. 46 (3): 175–82. doi:10.1016/S0165-0327(97)00156-0. PMID 9547115. 4. ^ Silveri MM, Rogowska J, McCaffrey A, Yurgelun-Todd DA (2011). "Adolescents at risk for alcohol abuse demonstrate altered frontal lobe activation during Stroop performance". Alcohol Clin Exp Res. 35 (2): 218–28. doi:10.1111/j.1530-0277.2010.01337.x. PMC 3058318. PMID 21073483. 5. ^ Cservenka A, Herting MM, Nagel BJ (2012). "Atypical frontal lobe activity during verbal working memory in youth with a family history of alcoholism". Drug Alcohol Depend. 123 (1–3): 98–104. doi:10.1016/j.drugalcdep.2011.10.021. PMC 3294260. PMID 22088655. 6. ^ Showraki, Mostafa (2013). ADHD: Revisited. Kindle Books, Amazon. 7. ^ a b Willis, T.; La Vigna, G.W. (2004). "Tip Sheet – Positive Behaviour Support Model" (PDF). Disability WA. Retrieved 2009-01-30. ## External links[edit] * The Online Disinhibition Effect * Social Behaviour In Cyberspace * External Inhibition & Disinhibition * v * t * e Psychopathy Contexts * In fiction * In the workplace Characteristics * Anti-social behaviour * Bold * Callous * Diminished empathy * Disinhibited * Grandiose * Impulsive * Lack of guilt * Manipulative * Pathological lying * Remorseless * Shallow affect * Superficially charming Related topics * Antisocial personality disorder * Conduct disorder * Dark triad * Flying monkeys * History of psychopathy * Juvenile delinquency * Machiavellianism * Macdonald triad * Narcissism * Psychopathic Personality Inventory * Psychopathy Checklist * Sadistic personality disorder * Sexual sadism disorder * Sociopathy Notable theorists * Hervey M. Cleckley * George E. Partridge * Robert D. Hare [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Disinhibition	c0424296	27,052	wikipedia	https://en.wikipedia.org/wiki/Disinhibition	2021-01-18T18:51:40	{"wikidata": ["Q5282244"]}
Human disease Saint Louis encephalitis virus Electron micrograph of Saint Louis encephalitis virus seen in a mosquito salivary gland Virus classification (unranked): Virus Realm: Riboviria Kingdom: Orthornavirae Phylum: Kitrinoviricota Class: Flasuviricetes Order: Amarillovirales Family: Flaviviridae Genus: Flavivirus Species: Saint Louis encephalitis virus Synonyms * St. Louis encephalitis virus[1] * St. Louis virus[2] Saint Louis encephalitis SpecialtyInfectious disease Saint Louis encephalitis is a disease caused by the mosquito-borne Saint Louis encephalitis virus. Saint Louis encephalitis virus is related to Japanese encephalitis virus and is a member of the family Flaviviridae. This disease mainly affects the United States, including Hawaii.[3] Occasional cases have been reported from Canada, Mexico and the Caribbean, including the Greater Antilles, Trinidad and Tobago, and Jamaica.[3] ## Contents * 1 Signs and symptoms * 2 Transmission * 3 Genetics * 4 Treatment * 5 Epidemiology * 6 History * 7 References * 8 External links ## Signs and symptoms[edit] The majority of infections result in mild illness, including fever and headache. When infection is more severe the person may experience headache, high fever, neck stiffness, stupor, disorientation, coma, tremors, occasional convulsions and spastic paralysis. Fatality ranges from 3–30%. Elderly people are more likely to have a fatal infection. ## Transmission[edit] Mosquitoes, primarily from the genus Culex, become infected by feeding on birds infected with the Saint Louis encephalitis virus. The most common vector of this disease within the genus Culex is Culex pipiens, also known as the common house mosquito. [4] Infected mosquitoes then transmit the Saint Louis encephalitis virus to humans and animals during the feeding process. The Saint Louis encephalitis virus grows both in the infected mosquito and the infected bird, but does not make either one sick. Only infected mosquitoes can transmit Saint Louis encephalitis virus. Once a human has been infected with the virus it is not transmissible from that individual to other humans. ## Genetics[edit] Five evolutionary genetic studies of SLE virus have been published of which four[5][6][7][8] focused on phylogeny, genetic variation, and recombination dynamics by sequencing the envelope protein gene and parts of other genes. A recent evolutionary study[9] based on 23 new full open reading frame sequences (near-complete genomes) found that the North American strains belonged to a single clade. Strains were isolated at different points in time (from 1933 to 2001) which allowed for the estimation of divergence times of SLE virus clades and the overall evolutionary rate. Furthermore, this study found an increase in the effective population size of the SLE virus around the end of the 19th century that corresponds to the split of the latest North American clade, suggesting a northwards colonization of SLE virus in the Americas, and a split from the ancestral South American strains around 1892.[10] Scans for natural selection showed that most codons of the SLE virus ORF were evolving neutrally or under negative selection. Positive selection was statistically detected only at one single codon coding for amino acids belonging to the hypothesized N-linked glycosylation site of the envelope protein. Nevertheless, the latter can be due to selection in vitro (laboratory) rather than in vivo (host). In an independent study[8] 14 out of 106 examined envelope gene sequences were found not to contain a specific codon at position 156 coding for this glycosylation site (Ser→Phe/Tyr). Another study estimated the evolutionary rate to be 4.1 × 10−4 substitutions/site/year (95% confidence internal 2.5-5.7 × 10−4 substitutions/site/year).[11] The virus seems to have evolved in northern Mexico and then spread northwards with migrating birds. ## Treatment[edit] There are no vaccines or any other treatments specifically for Saint Louis encephalitis virus, although one study showed that early use of interferon alfa-2b may decrease the severity of complications.[12] ## Epidemiology[edit] Human incidence of Saint Louis encephalitis in the United States, 1964-1998. In the United States an average of 128 cases of Saint Louis encephalitis are recorded annually. In temperate areas of the United States, Saint Louis encephalitis cases occur primarily in the late summer or early fall. In the southern United States where the climate is milder Saint Louis encephalitis can occur year-round. ## History[edit] The name of the virus goes back to 1933 when within five weeks in autumn an encephalitis epidemic of explosive proportions broke out in the vicinity of St. Louis, Missouri, and the neighboring St. Louis County.[13][14] Over 1,000 cases were reported to the local health departments and the newly constituted National Institutes of Health of the United States was appealed to for epidemiological and investigative expertise.[15] The previously unknown virus that caused the epidemic was isolated by the NIH team first in monkeys and then in white mice.[16] ## References[edit] 1. ^ Siddell, Stuart (April 2017). "Change the names of 43 virus species to accord with ICVCN Code, Section 3-II, Rule 3.13 regarding the use of ligatures, diacritical marks, punctuation marks (excluding hyphens), subscripts, superscripts, oblique bars and non-Latin letters in taxon names" (ZIP). International Committee on Taxonomy of Viruses (ICTV). Retrieved 29 April 2019. 2. ^ ICTV 5th Report Francki, R. I. B., Fauquet, C. M., Knudson, D. L. & Brown, F. (eds)(1991). Classification and nomenclature of viruses. Fifthreport of the International Committee on Taxonomy of Viruses. Archives of Virology Supplementum 2, p226 https://talk.ictvonline.org/ictv/proposals/ICTV%205th%20Report.pdf 3. ^ a b Mavian, Carla; Dulcey, Melissa; Munoz, Olga; Salemi, Marco; Vittor, Amy; Capua, Ilaria (25 December 2018). "Islands as Hotspots for Emerging Mosquito-Borne Viruses: A One-Health Perspective". Viruses. 11 (1): 11. doi:10.3390/v11010011. PMC 6356932. PMID 30585228. 4. ^ "Saint Louis Encephalitis". Centers for Disease Control and Prevention. November 20, 2009. Retrieved July 14, 2017. 5. ^ Kramer LD, Presser SB, Hardy JL, Jackson AO (1997). "Genotypic and phenotypic variation of selected Saint Louis encephalitis viral strains isolated in California". Am. J. Trop. Med. Hyg. 57 (2): 222–9. doi:10.4269/ajtmh.1997.57.222. PMID 9288820. 6. ^ Kramer LD, Chandler LJ (2001). "Phylogenetic analysis of the envelope gene of St. Louis encephalitis virus". Arch. Virol. 146 (12): 2341–55. doi:10.1007/s007050170007. PMID 11811684. S2CID 24755534. 7. ^ Twiddy SS, Holmes EC (2003). "The extent of homologous recombination in members of the genus Flavivirus". J. Gen. Virol. 84 (Pt 2): 429–40. doi:10.1099/vir.0.18660-0. PMID 12560576. 8. ^ a b May FJ, Li L, Zhang S, Guzman H, Beasley DW, Tesh RB, Higgs S, Raj P, Bueno R, Randle Y, Chandler L, Barrett AD (2008). "Genetic variation of St. Louis encephalitis virus". J. Gen. Virol. 89 (Pt 8): 1901–10. doi:10.1099/vir.0.2008/000190-0. PMC 2696384. PMID 18632961. 9. ^ Baillie GJ, Kolokotronis SO, Waltari E, Maffei JG, Kramer LD, Perkins SL (2008). "Phylogenetic and evolutionary analyses of St. Louis encephalitis virus genomes". Mol. Phylogenet. Evol. 47 (2): 717–28. doi:10.1016/j.ympev.2008.02.015. PMID 18374605. 10. ^ "Solving The Mystery Of St. Louis Encephalitis". American Museum of Natural History. 30 July 2008. Retrieved 28 July 2019. 11. ^ Auguste AJ, Pybus OG, Carrington CV (2009). "Evolution and dispersal of St. Louis encephalitis virus in the Americas". Infect. Genet. Evol. 9 (4): 709–15. doi:10.1016/j.meegid.2008.07.006. PMID 18708161. 12. ^ Rahal JJ, Anderson J, Rosenberg C, Reagan T, Thompson LL (2004). "Effect of interferon-alpha2b therapy on St. Louis viral meningoencephalitis: clinical and laboratory results of a pilot study". J. Infect. Dis. 190 (6): 1084–7. doi:10.1086/423325. PMID 15319857. 13. ^ "Encephalitis in St. Louis". American Journal of Public Health and the Nation's Health. 23 (10): 1058–60. October 1933. doi:10.2105/ajph.23.10.1058. PMC 1558319. PMID 18013846. 14. ^ Washington Post Magazine, October 8, 1933 15. ^ Bredeck JF (November 1933). "The Story of the Epidemic of Encephalitis in St. Louis". American Journal of Public Health and the Nation's Health. 23 (11): 1135–40. doi:10.2105/AJPH.23.11.1135. PMC 1558406. PMID 18013860. 16. ^ Edward A. Beeman: Charles Armstrong, M.D.: A Biography; 2007; p. 305; also online here (PDF). ## External links[edit] Classification D * ICD-10: A83.3 * ICD-9-CM: 062.3 * MeSH: D004674 * DiseasesDB: 29860 * United States Centers for Disease Control and Prevention. Saint Louis encephalitis. * St. Louis Encephalitis at eMedicine * The Encephalitis Society - A Global resource on Encephalitis * "St. Louis encephalitis virus". NCBI Taxonomy Browser. 11080. * v * t * e Zoonotic viral diseases (A80–B34, 042–079) Arthropod -borne Mosquito -borne Bunyavirales * Arbovirus encephalitides: La Crosse encephalitis * LACV * Batai virus * BATV * Bwamba Fever * BWAV * California encephalitis * CEV * Jamestown Canyon encephalitis * Tete virus * Tahyna virus * TAHV * Viral hemorrhagic fevers: Rift Valley fever * RVFV * Bunyamwera fever * BUNV * Ngari virus * NRIV Flaviviridae * Arbovirus encephalitides: Japanese encephalitis * JEV * Australian encephalitis * MVEV * KUNV * Saint Louis encephalitis * SLEV * Usutu virus * West Nile fever * WNV * Viral hemorrhagic fevers: Dengue fever * DENV-1-4 * Yellow fever * YFV * Zika fever * Zika virus Togaviridae * Arbovirus encephalitides: Eastern equine encephalomyelitis * EEEV * Western equine encephalomyelitis * WEEV * Venezuelan equine encephalomyelitis * VEEV * Chikungunya * CHIKV * O'nyong'nyong fever * ONNV * Pogosta disease * Sindbis virus * Ross River fever * RRV * Semliki Forest virus Reoviridae * Banna virus encephalitis Tick -borne Bunyavirales * Viral hemorrhagic fevers: Bhanja virus * Crimean–Congo hemorrhagic fever (CCHFV) * Heartland virus * Severe fever with thrombocytopenia syndrome (Huaiyangshan banyangvirus) * Tete virus Flaviviridae * Arbovirus encephalitides: Tick-borne encephalitis * TBEV * Powassan encephalitis * POWV * Viral hemorrhagic fevers: Omsk hemorrhagic fever * OHFV * Kyasanur Forest disease * KFDV * AHFV * Langat virus * LGTV Orthomyxoviridae * Bourbon virus Reoviridae * Colorado tick fever * CTFV * Kemerovo tickborne viral fever Sandfly -borne Bunyavirales * Adria virus (ADRV) * Oropouche fever * Oropouche virus * Pappataci fever * Toscana virus * Sandfly fever Naples virus Rhabdoviridae * Chandipura virus Mammal -borne Rodent -borne Arenaviridae * Viral hemorrhagic fevers: Lassa fever * LASV * Venezuelan hemorrhagic fever * GTOV * Argentine hemorrhagic fever * JUNV * Brazilian hemorrhagic fever * SABV * Bolivian hemorrhagic fever * MACV * LUJV * CHPV Bunyavirales * Hemorrhagic fever with renal syndrome * DOBV * HTNV * PUUV * SEOV * AMRV * THAIV * Hantavirus pulmonary syndrome * ANDV * SNV Herpesviridae * Murid gammaherpesvirus 4 Bat -borne Filoviridae * BDBV * SUDV * TAFV * Marburg virus disease * MARV * RAVV Rhabdoviridae * Rabies * ABLV * MOKV * DUVV * LBV * CHPV Paramyxoviridae * Henipavirus encephalitis * HeV * NiV Coronaviridae * SARS-related coronavirus * SARS-CoV * MERS-CoV * SARS-CoV-2 Primate -borne Herpesviridae * Macacine alphaherpesvirus 1 Retroviridae * Simian foamy virus * HTLV-1 * HTLV-2 Poxviridae * Tanapox * Yaba monkey tumor virus Multiple vectors Rhabdoviridae * Rabies * RABV * Mokola virus Poxviridae * Monkeypox Taxon identifiers * Wikidata: Q19838321 * IRMNG: 11460864 * Biology portal * Medicine 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Saint Louis encephalitis	c0014060	27,053	wikipedia	https://en.wikipedia.org/wiki/Saint_Louis_encephalitis	2021-01-18T19:06:20	{"mesh": ["D004674"], "umls": ["C0014060"], "orphanet": ["83484"], "wikidata": ["Q567660"]}
Familial periodic paralysis is a disease characterized by sudden attacks of weakness and paralysis. Weakness is recurrent, affecting mainly the limbs, and is often brought on by exercising or eating too many or too few carbohydrates. There are 4 forms of familial periodic paralysis: hypokalemic, hyperkalemic, thyrotoxic, and Andersen-Tawil syndrome. In the hypokalemic form, the paralysis is caused by low levels of potassium. In the hyperkalemic form, the paralysis is caused by high levels of potassium in the blood. In the thyrotoxic form, the paralysis is caused by low levels of potassium in the blood and an overactive thyroid gland (hyperthyroidism). In Andersen-Tawil syndrome, potassium levels can be high, low, or normal. Mutations in the CACNA1S and SCN4A genes cause hypokalemic periodic paralysis. The hyperkalemic form is due to mutations in SCN4A gene. The underlying cause of the thyrotoxic form is unknown. Mutations in the KCNJ2 gene cause Andersen-Tawil syndrome. Treatment is focused on correcting the levels of potassium in the blood and preventing episodes with lifestyle changes. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Familial periodic paralysis	c0030443	27,054	gard	https://rarediseases.info.nih.gov/diseases/6422/familial-periodic-paralysis	2021-01-18T18:00:32	{"mesh": ["D010245"], "orphanet": ["371433"], "synonyms": ["Genetic periodic paralysis"]}
## Description Poland syndrome consists of unilateral absence or hypoplasia of the pectoralis muscle, most frequently involving the sternocostal portion of the pectoralis major muscle, and a variable degree of ipsilateral hand and digit anomalies, including symbrachydactyly. Sometimes called Poland sequence, it was first described by Poland (1841). Poland syndrome is most commonly a sporadic condition (David, 1982; Opitz, 1982), but familial cases have been reported. Clinical Features McGillivray and Lowry (1977) ascertained 44 cases of Poland syndrome in British Columbia. There were no familial cases. There was a male predominance (27:17). All had absence of the sternal portion of the pectoralis major muscle with variable changes in the breasts and nipples. There was variable involvement of the hand and arm, with 4 patients having normal hands. Paternal age was elevated, but all 24 children of 8 affected adults were unaffected. David and Winter (1985) reported a family in which males in 3 successive generations had unilateral absence of the pectoralis major, serratus anterior, and latissimus dorsi muscles. The authors pointed out that association of absence of other muscles around the shoulder girdle is frequent with pectoralis absence, that the associated abnormality may limit the use of the latissimus muscle in reconstructive surgery (Hester and Bostwick, 1982), and that computerized tomography may be useful in determining the presence of other abnormalities (Suzuki et al., 1983). Gross-Kieselstein and Shalev (1987) reported a Poland-like abnormality in 2 brothers. The features were congenital absence of the trapezius, pectoralis, supraspinatus, and serratus anterior muscles bilaterally. Fraser et al. (1989) suggested that isolated pectoralis major muscle defects should be included in the spectrum of anomalies characterized as the Poland sequence. Riccardi (1978) described unilateral gluteal hypoplasia and brachysyndactyly and proposed that it was the lower limb equivalent of the Poland anomaly. In support of Riccardi's view, Parano et al. (1995) reported on an extended family in which 3 individuals, all women, had unilateral gluteal hypoplasia and the propositus in addition had unilateral hypoplasia of a pectoral muscle. Another relative in this family had unilateral symbrachydactyly of the distal phalanges of one foot. Corona-Rivera et al. (1997) reported another instance of a possible lower extremity counterpart of Poland sequence. Gluteal and lower extremity hypoplasia with ipsilateral toe brachysyndactyly was noted in a 23-year-old woman. Since no neurologic deficit was found, and electromyographic and nerve conduction studies in the affected limb were normal, they proposed a vascular origin which would involve the external iliac artery supply analogous to the disruption of the subclavian artery supply in the upper extremity Poland sequence. Czeizel et al. (1990) reported 18 typical cases of Poland sequence; 1 case was familial. The father had absence of the left pectoralis major muscle and severe hypoplasia of the left thumb with partial syndactyly between fingers 2 and 3, while the son had mild hypoplasia of the left pectoralis major muscle, severe hypoplasia of the left thumb, and mild hypoplasia of the right thumb. Czeizel et al. (1990) suggested that the disorder in this family may represent a separate pectoralis-radial defect with dominant inheritance such as that described by Konig and Lenz (1983). Karnak et al. (1998) described what they believed to be the first known case of bilateral Poland anomaly. A 6-year-old girl had bilateral absence of pectoralis major muscles, hypoplasia of the breasts and nipples, symmetric chest wall deformity, and bilateral hand anomaly. Shipkov and Anastassov (2003) questioned the existence of 'bilateral Poland anomaly.' They noted that 'classic Poland syndrome' is defined as a unilateral entity and that their clinical observations supported the idea that Poland syndrome is only unilateral. Shipkov and Anastassov (2003) agreed with Maroteaux and Le Merrer (1998) who had suggested the term 'thoracic dysplasia' for cases of supposed 'bilateral Poland anomaly.' ### Associated Syndromes Gadoth et al. (1979) reported a patient with Moebius syndrome (157900) and Poland anomaly. They suggested a common fetal mesodermal defect. Parker et al. (1981) reported at least 12 well-documented cases of association of Poland and Moebius syndromes. They concluded that the association represented a formal genesis malformation syndrome. Verzijl et al. (2003) found that 4 of 37 (11%) Dutch patients with Moebius syndrome also had Poland syndrome. Features included dextrocardia, agenesis of the pectoralis muscle, aplasia of the abdominal muscles, mammary hypoplasia, agenesis of the nipple, and various hand and finger anomalies. Der Kaloustian et al. (1991) described 2 families in which the Poland anomaly and the Adams-Oliver syndrome (100300) were coexistent. They hypothesized that the Poland anomaly and the Adams-Oliver syndrome result from the interruption of early embryonic blood supply in the subclavian arteries, and that the gene predisposing to this interruption follows an autosomal dominant pattern of inheritance. Cobben et al. (1992) described a 3-year-old boy with features of both Poland anomaly and Goldenhar syndrome (164210). Erol et al. (2004) reported a 7-year-old girl of Turkish origin with Klippel-Feil syndrome (KFS; see 118100) and Poland anomaly. She had the typical triad of KFS, including very short neck, low occipital hairline, and reduced bilateral neck movements. Radiographic examination showed fusion of C1 and C2 vertebrae. She also had absence of the right pectoralis muscle, hypoplastic right breast, hypoplastic costochondral junctions, and hypoplastic sternum consistent with Poland anomaly. She had no cardiac, vascular, or renal anomalies. Erol et al. (2004) noted that a child with features of KFS, Poland anomaly, and Mobius syndrome (157900) had been reported by Issaivanan et al. (2002), who postulated a disruption in the subclavian artery supply. Baban et al. (2009) reported a 3.5-year-old girl who had bilateral asymmetric pectoral muscle defects, with complete agenesis on the left side and agenesis of the sternocostal head on the right side, nipple hypoplasia, left rib defect, and right hand symbrachydactyly. The authors reviewed previously reported cases with bilateral features and discussed etiologic hypotheses. Inheritance Trier (1965) found 2 instances of parent and child with Poland syndrome. Fuhrmann et al. (1971) reported a family with father-to-son transmission and referred to other cases. Later information suggested that the grandfather may also have been affected (Fuhrmann, 1972). David (1982) described 2 second cousins with typical left-sided Poland anomaly. Discounting for one or another reason the previously reported familial cases, he claimed that this was the first recorded instance of familial occurrence. Soltan and Holmes (1986) and Bartoshesky et al. (1986) observed Poland anomaly in one or more family members and unilateral terminal transverse hemimelia in others. They suggested that some 'inherited liability to a common predisposing event' was likely. Cobben et al. (1989) described affected mother and daughter. The mother had absence of the sternocostal portion of the pectoralis major muscle, and slightly hypoplastic ipsilateral breast and areola; the daughter had symbrachydactyly as well. Fraser et al. (1989) reported a family in which a boy had unilateral absence of the pectoralis major, and his male second cousin had full Poland sequence on the left. The authors suggested autosomal dominant inheritance with reduced penetrance. Pathogenesis David (1972) observed a high frequency of 'potentially noxious social and physical ante-natal influence.' Of 10 patients with Poland syndrome, he found that 5 were adopted and the mothers of the other 5 had attempted abortion in early pregnancy. Bouwes Bavinck and Weaver (1986) hypothesized that Poland syndrome, Klippel-Feil anomaly (118100), Moebius syndrome, isolated absence of pectoralis major with breast hypoplasia, isolated transverse limb defects, and Sprengel anomaly (184400) are each the result of interruption of the early embryonic blood supply in the subclavian arteries, the vertebral arteries and/or their branches. The term subclavian artery supply disruption sequence (SASDS) was suggested for this group of birth defects. They discussed causative mechanisms such as pressure on the vessel by edema. Fraser et al. (1989) suggested that isolated pectoralis major muscle defects should be included in the spectrum of anomalies postulated to result from disruption of blood supply in the embryonic subclavian and vertebral arteries, the site and degree of obstruction determining the sites and severity of the resulting anomalies. Hennekam and Hofstee (1990) reported a family in which the proband had Poland syndrome. An earlier pregnancy of the mother had produced a baby girl with a large lumbar neural tube defect and congenital hydrocephaly leading to death shortly after birth, and a first cousin of the mother had hemifacial microsomia. Hennekam and Hofstee (1990) proposed that this constellation supports the hypothesis of Stevenson et al. (1987) that neural tube defects may be produced by inadequate nutrient supply to the growing neural folds due to primary vascular abnormalities. Population Genetics In British Columbia, McGillivray and Lowry (1977) found an incidence of Poland syndrome of 1 per 32,000 live births. Czeizel et al. (1990) reported that in Hungary for the period 1975 to 1984 there was 1 case of full-blown Poland sequence in 87,550 births, including 12 cases with Poland sequence-type symbrachydactyly but without pectoralis major defect. The frequency came to 1 in 52,530. INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Dextrocardia (in left-sided Poland sequence) CHEST External Features \- Unilateral hypoplasia or absence of pectoralis major muscle \- Absence of pectoralis minor muscle Ribs Sternum Clavicles & Scapulae \- Sprengel anomaly \- Hypoplastic ribs \- Fused ribs Breasts \- Unilateral hypoplasia or absence of nipple \- Unilateral hypoplasia or absence of areola \- Unilateral absence of breast SKELETAL Spine \- Hemivertebrae Hands \- Unilateral syndactyly \- Unilateral brachydactyly \- Unilateral oligodactyly MUSCLE, SOFT TISSUES \- Hypoplasia of latissimus dorsi muscle \- Hypoplasia of serratus anterior muscle \- Hypoplasia of infraspinatus muscle \- Hypoplasia of supraspinatus muscle \- Hypoplasia of deltoid muscle MISCELLANEOUS \- All features are unilateral \- Occurs on right side in 75% of cases \- Three times more common in males \- Majority of cases are sporadic \- Pedigrees compatible with autosomal dominant inheritance have been reported \- Poland syndrome can be associated with Moebius syndrome ( 157900 ) \- Subclavian artery supply disruption in embryogenesis has been suggested as etiology ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	POLAND SYNDROME	c0032357	27,055	omim	https://www.omim.org/entry/173800	2019-09-22T16:36:13	{"doid": ["12961"], "mesh": ["D011045"], "omim": ["173800"], "icd-10": ["Q79.8"], "orphanet": ["2911"], "synonyms": ["Alternative titles", "POLAND SYNDACTYLY", "POLAND ANOMALY", "POLAND SEQUENCE"]}
Thiemann disease is a very rare genetic necrotic bone disorder characterized clinically by painless swelling of the proximal interphalangeal joints associated with osteonecrosis of epiphyses followed by osteoarthritic changes, with onset before 25 years of age and often a benign course. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Thiemann disease, familial form	c0264081	27,056	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3314	2021-01-23T17:52:04	{"gard": ["4131"], "mesh": ["C537144"], "omim": ["165700"], "icd-10": ["M93.2"], "synonyms": ["Aseptic necrosis of phalangeal epiphyses", "Osteochondrosis of phalangeal epiphyses"]}
XK aprosencephaly syndrome is a very rare syndromic type of cerebral malformation characterized by aprosencephaly (absence of telencephalon and diencephalon), oculo-facial anomalies (i.e. ocular hypotelorism or cyclopia, malformation/absence of nasal structures, cleft lip), preaxial limb defects (i.e. hypoplastic hands, absent halluces) and various other anomalies including ambiguous genitalia, imperforate anus, and vertebral anomalies. The syndrome is thought to have an autosomal recessive mode of inheritance. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	XK aprosencephaly syndrome	c0795952	27,057	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3469	2021-01-23T18:59:14	{"gard": ["424"], "mesh": ["C536767"], "omim": ["207770"], "umls": ["C0431348", "C0795952"], "icd-10": ["Q04.3"], "synonyms": ["Garcia-Lurie syndrome", "XK syndrome", "XK-aprosencephaly"]}
A number sign (#) is used with this entry because of evidence that the phenotype can be caused by mutations in the HOXA13 gene (142959). Clinical Features Guttmacher (1993) suggested that a disorder he observed in a father and son and daughter was distinct from the hand-foot-genital (HFG) syndrome (140000) which it resembled in some ways. All 3 individuals were born with preaxial deficiencies of the hands and feet and postaxial polydactyly of the hands. Both the father and the son had glanular hypospadias. Guttmacher (1993) thought the condition could be distinguished from the HFG syndrome by the shortness of the second toes in all 3 affected persons but particularly by the presence of postaxial polydactyly which, he stated, had never been noted in the HFG syndrome. Molecular Genetics Because of similarities to the hand-foot-genital syndrome, which is caused by mutations in the HOXA13 gene, Innis et al. (2002) reinvestigated the family reported by Guttmacher (1993) and found a specific HOXA13 missense mutation, gln50 to leu (Q50L; 142959.0005). The mutation had arisen on an allele already carrying a novel 2-bp deletion in the promoter region of the gene. The deletion produced no detectable abnormalities on its own, but may have contributed to the phenotype in the affected individuals, which differed somewhat from that of hand-foot-genital syndrome. INHERITANCE \- Autosomal dominant GENITOURINARY External Genitalia (Male) \- Glanular hypospadias SKELETAL Hands \- Postaxial polydactyly of hands \- Short thumbs \- Limited range of motion of interphalangeal joints \- Brachydactyly, mild (5th finger) Feet \- Rudimentary halluces \- Uniphalangeal second toes SKIN, NAILS, & HAIR Nails \- Missing nail on halluces and second toes MISCELLANEOUS \- Based on description of 3 individuals in 1 family MOLECULAR BASIS \- Caused by mutation in the homeobox A13 gene (HOXA13, 142959.0005 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	PREAXIAL DEFICIENCY, POSTAXIAL POLYDACTYLY, AND HYPOSPADIAS	c1867801	27,058	omim	https://www.omim.org/entry/176305	2019-09-22T16:35:46	{"mesh": ["C538278"], "omim": ["176305"], "orphanet": ["2957"], "synonyms": ["Alternative titles", "GUTTMACHER SYNDROME"]}
Hyperphenylalaninemia Hyperphenylalaninemia can be inherited in an autosomal recessive manner. SpecialtyEndocrinology Hyperphenylalaninemia is a medical condition characterized by mildly or strongly elevated concentrations of the amino acid phenylalanine in the blood. Phenylketonuria (PKU) can result in severe hyperphenylalaninemia.[1] Phenylalanine concentrations ([phe]) are routinely screened in newborns by the neonatal heel prick (Guthrie test), which takes a few drops of blood from the heel of the infant. Standard [phe] concentrations in unaffected persons are about 60µM: [phe] concentrations in persons with untreated phenylketonuria may be many times that (600µM to 2400µM), which indicate that the child is at risk for severe intellectual disability. Phenylketonuria is classed as an autosomal recessive condition: in heterozygous form, [phe] shows a moderate elevation, perhaps two-fold over that of unaffected homozygotes, which is classified as hyperphenylalaninemia (hyper- \+ phenylalanine \+ -emia = high [phe] in blood). ## Contents * 1 Symptoms and signs * 2 Cause * 3 Treatment * 4 Outcome * 5 References * 6 External links ## Symptoms and signs[edit] The coloration of the skin, hair, and eyes is different in children with PKU. This is caused by low levels of tyrosine, whose metabolic pathway is blocked by deficiency of PAH. Another skin alteration that might occur is the presence of irritation or dermatitis. The child's behaviour may be influenced as well due to augmented levels of phenethylamine which in turn affects levels of other amines in the brain. Psychomotor function may be affected and observed to worsen progressively.[citation needed] ## Cause[edit] People with the genotype for PKU are unaffected in utero, because maternal circulation prevents buildup of [phe]. After birth, PKU in newborns is treated by a special diet with highly restricted phenylalanine content. Persons with genetic predisposition to PKU have normal mental development on this diet. Previously, it was thought safe to withdraw from the diet in the late teens or early twenties, after the central nervous system was fully developed; recent studies suggest some degree of relapse, and a continued phenylalanine-restricted diet is now recommended.[2] PKU or hyperphenylalaninemia may also occur in persons without the PKU genotype. If the mother has the PKU genotype but has been treated so as to be asymptomatic, high levels of [phe] in the maternal blood circulation may affect the non-PKU fetus during gestation. Mothers successfully treated for PKU are advised to return to the [phe]-restricted diet during pregnancy.[citation needed] A small subset of patients with hyperphenylalaninemia shows an appropriate reduction in plasma phenylalanine levels with dietary restriction of this amino acid; however, these patients still develop progressive neurologic symptoms and seizures and usually die within the first 2 years of life ("malignant" hyperphenylalaninemia). These infants exhibit normal phenylalanine hydroxylase (PAH) enzymatic activity but have a deficiency in dihydropteridine reductase (DHPR), an enzyme required for the regeneration of tetrahydrobiopterin (THB or BH4), a cofactor of PAH.[citation needed] Less frequently, DHPR activity is normal but a defect in the biosynthesis of THB exists. In either case, dietary therapy corrects the hyperphenylalaninemia. However, THB is also a cofactor for two other hydroxylation reactions required in the syntheses of neurotransmitters in the brain: the hydroxylation of tryptophan to 5-hydroxytryptophan and of tyrosine to L-dopa. It has been suggested that the resulting deficit in the CNS neurotransmitter activity is, at least in part, responsible for the neurologic manifestations and eventual death of these patients.[3] Hyperphenylalaninemia most is commonly diagnosed by newborn screening and must be distinguished from classic PKU by confirmatory testing at an experienced center. Some cases in adult women have been detected using maternal screening programs or following birth of children with birth defects. Elevated phenylalanine levels are associated with neuropsychological effects.[citation needed] ## Treatment[edit] Maintain plasma phenylalanine values in therapeutic range of 120 to 360 mM using a diet that restricts phenylalanine but otherwise nutritionally complete. Treatment for life is recommended to reduce the risk of long term neuropsychiatric problems and reduce the risk of maternal PKU syndrome.[citation needed] ## Outcome[edit] With treatment the outcome is excellent. Most infants with classic PKU who are treated within the first 10 days of life achieve normal intelligence. However learning problems are more frequent than in unaffected peers.[citation needed] ## References[edit] 1. ^ "OMIM Entry # 261600 - Phenylketonuria; PKU". omim.org. Archived from the original on 2014-05-29. Retrieved 2016-06-03. 2. ^ van Wegberg AM, MacDonald A, Ahring K, Bélanger-Quintana A, Blau N, Bosch AM, et al. (October 2017). "The complete European guidelines on phenylketonuria: diagnosis and treatment". Orphanet Journal of Rare Diseases. 12 (1): 162. doi:10.1186/s13023-017-0685-2. PMC 5639803. PMID 29025426. 3. ^ Lieberman M, Marks AD (2013). Marks' Basic Medical Biochemistry (fourth ed.). ISBN 978-1-60831-572-7. ## External links[edit] Classification D * ICD-10: E70.1 (also includes non-classic PKU) * ICD-9-CM: 270.1 (PKU) * OMIM: 261600 261630 * MeSH: D010661 External resources * Orphanet: 238583 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Hyperphenylalaninemia	c0751435	27,059	wikipedia	https://en.wikipedia.org/wiki/Hyperphenylalaninemia	2021-01-18T19:02:39	{"mesh": ["D010661"], "umls": ["C0751435"], "icd-9": ["270.1"], "icd-10": ["E70.1"], "wikidata": ["Q5898279"]}
Meningococcal meningitis is an acute bacterial disease caused by Neisseria meningitides that presents usually, but not always, with a rash (non blanching petechial or purpuric rash), progressively developing signs of meningitis (fever, vomiting, headache, photophobia, and neck stiffness) and later leading to confusion, delirium and drowsiness. Neck stiffness and photophobia are often absent in infants and young children who may manifest nonspecific signs such as irritability, inconsolable crying, poor feeding, and a bulging fontanel. Meningococcal meningitis may also present as part of early or late onset sepsis in neonates. The disease is potentially fatal. Surviving patients may develop neurological sequelae that include sensorineural hearing loss, seizures, spasticity, attention deficits and intellectual disability. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Meningococcal meningitis	c0025294	27,060	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=33475	2021-01-23T17:40:03	{"mesh": ["D008585"], "umls": ["C0025294"], "icd-10": ["A39.0+", "G01*"]}
Maffucci syndrome is a very rare genetic bone and skin disorder characterized by multiple enchondromas, leading to bone deformities, combined with multiple dark, irregularly shaped hemangiomas or less commonly lymphangiomas. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Maffucci syndrome	c0024454	27,061	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=163634	2021-01-23T18:22:36	{"gard": ["6958"], "mesh": ["D004687"], "omim": ["614569"], "umls": ["C0024454"], "icd-10": ["Q78.4"]}
Cavitary myiasis is a rare parasitic disease characterized by the infestation of natural body cavities (e.g. aural, nasal, oral, urogenital myiasis) and internal organs (e.g. cerebral myiasis, ophthalmomyiasis, intestinal and tracheopulmonary myiasis) with dipteran larvae. Clinical presentation is variable depending on the affected site(s) and degree of infestation and include foreign-body sensation (with or without movement sensation), hemorrhage, pain, edema, sensory loss, malodor, and pruritus, among others. Neurological features (e.g. motor deficits, seizures, reduced mental status, extrapyramidal signs) have been reported in cerebral myiasis. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Cavitary myiasis	c4707154	27,062	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=165958	2021-01-23T18:43:16	{"icd-10": ["B87.8"]}
A number sign (#) is used with this entry because of evidence that 3MC syndrome-1 is caused by homozygous mutation in the MASP1 gene (600521) on chromosome 3q27. Description The term '3MC syndrome' encompasses 4 rare autosomal recessive disorders that were previously designated the Carnevale, Mingarelli, Malpuech, and Michels syndromes, respectively. The main features of these syndromes are facial dysmorphism that includes hypertelorism, blepharophimosis, blepharoptosis, and highly arched eyebrows, which are present in 70 to 95% of cases. Cleft lip and palate, postnatal growth deficiency, cognitive impairment, and hearing loss are also consistent findings, occurring in 40 to 68% of cases. Craniosynostosis, radioulnar synostosis, and genital and vesicorenal anomalies occur in 20 to 30% of cases. Rare features include anterior chamber defects, cardiac anomalies, caudal appendage, umbilical hernia (omphalocele), and diastasis recti (summary by Rooryck et al., 2011). ### Genetic Heterogeneity of 3MC Syndrome Also see 3MC syndrome-2 (3MC2; 265050), caused by mutation in the COLEC11 gene (612502), and 3MC syndrome-3 (3MC3; 248340), caused by mutation in the COLEC1 gene (607620). Clinical Features Michels et al. (1978) described 3 brothers and a sister with the eyelid triad of blepharophimosis, blepharoptosis and epicanthus inversus, plus a developmental defect of the anterior segment of the eye leading to corneal stromal opacities, limitation of upward gaze, cleft lip-palate, and some minor skeletal abnormalities in the form of spina bifida occulta, cranial asymmetry, abnormality of the occipital bone, and radioulnar synostosis. The fifth finger was short. The family was Mexican-American. The parents were not known to be consanguineous and were unaffected. Cohen (1986) designated the disorder Michels syndrome. Cunniff and Jones (1990) reported an affected girl whose parents were unrelated. Guion-Almeida and Rodini (1995) reported the case of a Brazilian girl born of first-cousin parents and presenting with craniosynostosis, telecanthus, blepharophimosis, blepharoptosis, epicanthus inversus, cleft lip and palate, skeletal defects, and hearing loss. Al Kaissi et al. (2007) suggested that the patient reported by Guion-Almeida and Rodini (1995) had Carnevale syndrome (265050). Titomanlio et al. (2005) reported a female infant of healthy nonconsanguineous Chinese parents who exhibited facial dysmorphism including blepharophimosis, blepharoptosis, epicanthus inversus, telecanthus, bilateral cleft lip and palate, and micrognathia. Her anterior fontanel was extremely large. She also had low-set ears, 2 accessory nipples, a tuberous angioma on the thorax, a supraumbilical depression, small hands with bilateral short fifth fingers, broad feet, and severe axial hypotonia. When last seen at 2 years, 10 months of age, she had mild psychomotor retardation and no speech, and a moderate bilateral conductive hearing loss was noted. Titomanlio et al. (2005) reviewed the phenotypic similarities between Michels syndrome, Malpuech syndrome (248340), and Carnevale syndrome (265050), and suggested that they may represent a single recessive spectrum rather than separate disorders. Titomanlio et al. (2005) proposed that the combined entity could be referred to as the '3MC syndrome' (Malpuech-Michels-Mingarelli-Carnevale syndrome); Mingarelli et al. (1996) had described 2 sisters with what the authors called ocular-skeletal-abdominal (OSA) syndrome (see 265050). Leal and Baptista (2007) reported 3 additional Brazilian cases of Michels syndrome: 2 brothers, aged 23 and 17 years, respectively, born to first-cousin parents, and an unrelated 11-year-old girl. The younger affected brother had a normal twin brother, and a fourth brother, who had died at 2 years of age from diarrhea, was reported to have had the same facial appearance as the 2 affected brothers. The younger affected brother also had short stature and sexual infantilism and was found to have growth hormone deficiency and secondary hypogonadism; the authors questioned whether these were manifestations of Michels syndrome. Leal and Baptista (2007) also noted that the affected girl did not have epicanthus inversus, although she displayed other key features of Michels syndrome, including blepharoptosis, blepharophimosis, telecanthus, and cleft lip/palate. The authors stated that these 3 cases brought the total number of published cases of Michels syndrome to 10. Leal et al. (2008) described a brother and sister with blepharoptosis, highly arched eyebrows, hearing loss, and caudal appendage. Blepharophimosis, periumbilical depression, and anterior chamber anomaly was present in the sister. Leal et al. (2008) noted that the sibs had features that overlap the Michels, Malpuech, Carnevale, and OSA syndromes. They concluded that the symptoms present in the sibs supported the suggestion of Titomanlio et al. (2005) that the disorders represent a single entity that might be termed the 3MC syndrome. Mapping In 2 families with 3MC syndrome, 1 of which was known to be consanguineous, Rooryck et al. (2011) performed homozygosity mapping and identified a 2.2-Mb shared region of identity by descent at chromosome 3q27. Molecular Genetics In 2 Turkish families with 3MC syndrome mapping to chromosome 3q27, Sirmaci et al. (2010) performed whole genome sequencing of candidate genes and identified homozygosity for a missense and a nonsense mutation in the MASP1 gene (600521.0004-600521.0005, respectively). In 2 families with 3MC syndrome mapping to chromosome 3q27, Rooryck et al. (2011) analyzed candidate genes and identified 2 homozygous missense mutations in the MASP1 gene (600521.0001 and 600521.0002, respectively) that segregated with the disorder in each family. Analysis of the MASP1 gene in 2 additional Brazilian families with 3MC syndrome, originally reported by Leal and Baptista (2007) and Leal et al. (2008), respectively, revealed homozygosity for a third missense mutation in affected individuals (600521.0003). Urquhart et al. (2016) ascertained an additional 13 patients from 12 families with 3MC syndrome, in whom they analyzed the MASP1 and COLEC11 genes. Two Israeli sibs were homozygous for a frameshift mutation in MASP1, and 5 unrelated patients were homozygous for 2 missense and 3 nonsense mutations in COLEC11, respectively. The remaining 6 patients, including 4 who were 'less typical' of 3MC syndrome, were negative for mutation in MASP1 and COLEC11. Urquhart et al. (2016) tabulated the clinical features of these patients and noted that all of the mutation-positive individuals had distinctive highly arched eyebrows with ptosis as well as more striking hypertelorism than mutation-negative individuals. The authors considered this facial phenotype to be a key diagnostic feature for the condition. They also found that a caudal appendage, usually taking the form of a cystic lesion over the sacrum, was a good indicator for mutation-positive individuals. Using DNA samples from 36 patients in 34 families with 3MC syndrome, Munye et al. (2017) screened for mutations in the MASP1 and COLEC11 genes and identified homozygosity for a nonsense mutation in MASP1 in a Pakistani patient, as well as homozygosity for mutations in COLEC11 in 3 unrelated patients. INHERITANCE \- Autosomal recessive GROWTH Other \- Postnatal growth retardation HEAD & NECK Head \- Microcephaly \- Large anterior fontanel Face \- Hypoplastic supraorbital ridges Ears \- Hearing loss, conductive Eyes \- Blepharophimosis \- Blepharoptosis \- Epicanthus inversus \- Hypertelorism \- High-arched eyebrows \- Conjunctival telangiectasia \- Glaucoma \- Anterior chamber anomalies \- Abnormal eye motility Mouth \- Cleft lip \- Cleft palate Teeth \- Dental crowding CARDIOVASCULAR Heart \- Patent ductus arteriosus \- Atrial septal defect \- Ventricular septal defect CHEST External Features \- Skin tag at xiphoid process Breasts \- Accessory nipple ABDOMEN External Features \- Periumbilical depression \- Omphalocele GENITOURINARY Kidneys \- Hydronephrosis SKELETAL Skull \- Craniosynostosis (lambdoid and coronal sutures) \- Skull asymmetry Spine \- Spina bifida occulta Limbs \- Radioulnar synostosis Hands \- Short fifth finger \- Fifth finger clinodactyly \- Fifth finger single interphalangeal crease Feet \- Short, broad feet SKIN, NAILS, & HAIR Skin \- Caudal appendage (sacral cyst) \- Sacral dimple NEUROLOGIC Central Nervous System \- Mental retardation, mild MOLECULAR BASIS \- Caused by mutation in the mannan-binding lectin serine protease-1 gene (MASP1, 600521.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	3MC SYNDROME 1	c0796059	27,063	omim	https://www.omim.org/entry/257920	2019-09-22T16:24:09	{"doid": ["0060575"], "mesh": ["C537738"], "omim": ["257920"], "orphanet": ["293843", "2506"], "synonyms": ["OCULOPALATOSKELETAL SYNDROME", "Craniofacial-ulnar-renal syndrome", "Alternative titles", "MICHELS SYNDROME, FORMERLY", "Malpuech-Michels-Mingarelli-Carnevale syndrome", "CRANIOSYNOSTOSIS WITH LID ANOMALIES"]}
A number sign (#) is used with this entry because of evidence that recurrent hydatidiform mole-3 (HYDM3) is caused by homozygous or compound heterozygous mutation in the MEI1 gene (608797) on chromosome 22q13. Description Hydatidiform mole is a human pregnancy with abnormal or no embryonic development and excessive trophoblastic proliferation. Partial hydatidiform moles have a triploid dispermic genome, with 2 sets of paternal chromosomes and 1 set of maternal chromosomes; complete hydatidiform moles have a diploid androgenetic genome with all chromosomes originating from 1 (monospermic) or 2 (dispermic) sperms, and no maternal chromosomes (summary by Nguyen et al., 2018). For a discussion of genetic heterogeneity of recurrent hydatidiform mole, see HYDM1 (231090). Clinical Features Nguyen et al. (2018) identified 2 unrelated women with complete hydatidiform mole and biallelic mutation in the MEI1 gene. The first woman (proband 1333) had a history of 4 miscarriages followed by 4 hydatidiform moles, all from spontaneous conception. In addition, she had 1 failed cycle of in vitro fertilization by intracytoplasmic sperm injection (ICSI). Two of her sisters had 1 and 3 miscarriages, respectively, and both underwent total abdominal hysterectomy because of several uterine fibroids. None of the 3 women had any live births. The second woman (proband 880) had 6 miscarriages and 1 complete hydatidiform mole. Her brother, who was infertile, had nonobstructive azoospermia and no Y chromosome deletions. Nguyen et al. (2018) retrieved all hydatidiform mole tissue from affected probands 1333 and 880. By morphologic evaluation, all tissues fulfilled pathologic criteria of complete hydatidiform mole, did not express p57(KIP2) (600856) in the nuclei of the cytotrophoblast and villous mesenchyme cells, were diploid by flow cytometry, androgenetic monospermic by microsatellite DNA marker genotyping, and did not have aneuploidies by SNP microarrays. Molecular Genetics To identify mutations responsible for recurrent hydatidiform mole, Nguyen et al. (2018) performed whole-exome sequencing on 65 women with recurrent hydatidiform moles (including all histopathologic and genotypic types), miscarriages, and infertility, who were negative for mutations in NLRP7 (609661) and KHDC3L (611687). Nguyen et al. (2018) identified biallelic deleterious mutations in 3 genes involved in meiotic double-strand breaks in 5 unrelated women. Two women (probands 1333 and 880) and affected family members carried mutations in the MEI1 gene (608797). Proband 1333, who had 4 miscarriages followed by 4 hydatidiform moles, and her 2 sisters, who had 1 and 3 miscarriages, respectively, were homozygous for a nonsense mutation in exon 28 (W1151X; 608797.0001). Proband 880, with 6 miscarriages and 1 complete hydatidiform mole, and her brother, with nonobstructive azoospermia and no Y chromosome deletions, were compound heterozygous for an invariant splice site mutation (608797.0002) and a 1-bp deletion (608797.0003). INHERITANCE \- Autosomal recessive GENITOURINARY External Genitalia (Male) \- Nonobstructive azoospermia (in the brother of an affected sister) Internal Genitalia (Female) \- Infertility PRENATAL MANIFESTATIONS Placenta & Umbilical Cord \- Gestational trophoblastic disease \- Hydatidiform mole MISCELLANEOUS \- Based on a report of 3 sisters and an unrelated woman (last curated May 2019) MOLECULAR BASIS \- Caused by mutation in the meiotic double-stranded break formation protein 1 gene (MEI1, 608797.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	HYDATIDIFORM MOLE, RECURRENT, 3	None	27,064	omim	https://www.omim.org/entry/618431	2019-09-22T15:41:58	{"omim": ["618431"]}
A rare genetic, neurodevelopmental syndrome characterized by hypothalamic-pituitary dysfunction with severe hypotonia and feeding deficits during the neonatal period followed by an excessive weight gain period with hyperphagia with a risk of severe obesity during childhood and adulthood, learning difficulties, deficits of social skills and behavioral problems or severe psychiatric problems. ## Epidemiology Prevalence at birth is estimated at 1/15,000-30,000 worldwide ## Clinical description The severe hypotonia at birth is associated with poor oral and social skills which remain, albeit less clinically evident, throughout life. Characteristic facial features (a narrow forehead, almond-shaped eyes, a thin upper lip and down-turned mouth), as well as very small hands and feet, are frequently observed. After this initial phase, followed by an excessive weight gain without changes in eating, the most striking signs appear: hyperphagia and absence of satiety often leading to severe obesity in affected children as young as three years of age. The situation may deteriorate quickly without strict control of food access. Other associated endocrine abnormalities include short stature due to a growth hormone (GH) deficiency, incomplete pubertal development due to hypogonadism of mixed (central and peripheral) origin, hypothyroidism, premature pubarche and, rarely, corticotropin deficiency. The degree of cognitive dysfunction varies widely but is mild/moderate in most of the individuals. It is associated with learning disabilities, and impaired speech and language development that are aggravated further by psychological and behavioral troubles, impaired social abilities, and control of emotions. Associated comorbidities may include diabetes, sleep-related breathing disorders, gastrointestinal problems, and infections. The Prader-Willi syndrome (PWS) phenotype also occurs in 10% of Fragile X syndrome. ## Etiology The disease is clinically and genetically heterogeneous. Frequently it is caused by either a paternally derived 15q11-q13 deletion, maternal disomy or, very rarely, imprinting defects in the same region. ## Diagnostic methods PWS should be suspected on the presentation of severe neonatal hypotonia, and confirmed by genetic testing which should include methylation analysis, fluorescent in situ hybridization and uniparental disomy testing. ## Differential diagnosis At birth, genetic testing should be used to exclude other causes of hypotonia. If the neonatal phenotype evokes PWS and the genetics are negative, genes for the Prader-Willi-like syndrome (PWS-like) should be searched. In older individuals, the differential diagnosis is of other syndromic obesities such as Bardet-Biedl syndrome, Alström syndrome and, particularly, PWS-like. ## Antenatal diagnosis Diagnosis may be suspected in the last trimester on detection of polyhydramnios, decreased fetal movements and abnormal positions of hand and feet with or without fetal growth restriction. Genetic testing can confirm diagnosis but note that comparative genomic hybridization is not sufficient to exclude PWS. ## Genetic counseling Most cases are sporadic; however, in rare cases dominant transmission may occur with 50% risk where the father carries the imprinting defect. ## Management and treatment Multidisciplinary management should be implemented very early, with particular attention paid to families with psychosocial difficulties. Principally, management is with a strict control of food access and exercise program and, growth hormone (GH) treatment. Associated comorbidities require systematic screening and evaluation. Currently, there are no approved medications to specifically improve the behavioral problems or degree of autonomy obtained. Clinical trials are ongoing for various drugs targeting hyperphagia and behavior. ## Prognosis Obesity is a major factor influencing morbidity and mortality. Early diagnosis, early multidisciplinary care and GH treatment have greatly improved the quality of life of affected children. GH treatment in particular has shown to stabilize body mass index, improve linear growth and adult height and, in children treated before 1 year of age, improve cognitive development. Adolescents benefit from continuing GH treatment Adults who have received GH as children have lower BMI and less comorbidities. Autonomies can be reached but not complete autonomy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Prader-Willi syndrome	c0032897	27,065	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=739	2021-01-23T17:01:17	{"gard": ["5575"], "mesh": ["D011218"], "omim": ["176270", "615547"], "umls": ["C0032897"], "icd-10": ["Q87.1"], "synonyms": ["Prader-Labhart-Willi syndrome"]}
A number sign (#) is used with this entry because of evidence that susceptibility to microvascular complications of diabetes-6 is associated with variation in the SOD2 gene (147460). For a discussion of genetic heterogeneity of susceptibility to microvascular complications of diabetes, see MVCD1 (603933). Molecular Genetics Among Japanese patients with type 2 diabetes (125853), Nomiyama et al. (2003) found a significantly higher frequency of the SOD2-VV genotype (147460.0001) than the AA or VA genotypes in patients with diabetic nephropathy (odds ratio, 0.46; p = 0.03). They concluded that the A16V polymorphism may be unrelated to the etiology of type 2 diabetes, but is associated with diabetic nephropathy in Japanese patients with type 2 diabetes. Mollsten et al. (2007) analyzed the SOD2 A16V polymorphism (rs4880) in 1,510 Finnish and Swedish patients with type 1 diabetes (222100), including 619 patients with overt diabetic nephropathy (albumin excretion rate greater than 200 micrograms/min) or renal replacement therapy, 336 with 'incipient' diabetic nephropathy (albumin excretion rate of 20-200 micrograms/min), and 555 controls, who had diabetes duration greater than 20 years without albuminuria or antihypertensive treatment. After controlling for age at onset, diabetes duration, hemoglobin A1C, smoking, and gender, the VV genotype was associated with an increase in the risk of diabetic nephropathy (odds ratio, 1.32; p = 0.049). Logistic regression analysis showed that the high-risk group, VV patients who had ever smoked, had a 2.52-fold increased risk for diabetic nephropathy compared to the low-risk group, supporting the hypothesis that oxidative stress contributes to the development of diabetic nephropathy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	MICROVASCULAR COMPLICATIONS OF DIABETES, SUSCEPTIBILITY TO, 6	c2675128	27,066	omim	https://www.omim.org/entry/612634	2019-09-22T16:00:57	{"omim": ["612634"], "synonyms": ["Alternative titles", "NEPHROPATHY, DIABETIC, SUSCEPTIBILITY TO"]}
Leukonychia totalis-acanthosis-nigricans-like lesions-abnormal hair syndrome is a rare, syndromic nail anomaly disorder characterized by the association of leukonychia totalis with acanthosis-nigricans-like lesions (occurring in the neck, axillae and abdomen regions) and hair dysplasia, manifesting with dry, brittle hair which presents an irregular pattern of complete or incomplete twists and an irregular surface with londitudinal furrows on electronic microscopy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Leukonychia totalis-acanthosis-nigricans-like lesions-abnormal hair syndrome	None	27,067	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=210133	2021-01-23T17:57:52	{"icd-10": ["Q82.8"]}
For background information on the major histocompatibility complex (MHC) and human leukocyte antigens (HLAs), see HLA-A (142800). Mapping Cann et al. (1983) found a restriction fragment that segregated with HLA-B8. Either the fragment carried the B8 specificity or represented another class I gene (or pseudogene) in linkage disequilibrium with HLA-B8. Dunham et al. (1987) used pulsed-field gel electrophoresis and 'cosmid walking' to establish a molecular map of the MHC region. They concluded that the MHC spans 3,800 kb. The HLA-B locus lies about 250 kb on the telomeric side of the tumor necrosis factor genes (see TNFA; 191160). Spies et al. (1989) found that the HLA-B gene is 210 kb from the TNFA and TNFB (153440) genes. The class III gene C2 is separated from the HLA-B gene by 600 kb. Spies et al. (1989) concluded that a 600-kb DNA segment between C2 and HLA-B contains a minimum of 19 genes. In addition to BAT1 (142560) through BAT5 (142620), which had been localized to the vicinity of the TNFA and TNFB genes, 4 genes, called BAT6 through BAT9, were mapped near C2 within a 120-kb region that also includes a pair of heat-shock protein genes (see 140550). A large number of BssHII and SacII restriction sites, known to indicate the presence of multiple islands of CPG-rich sequences and in turn the association of expressed genes, occurred within 140 kb of DNA upstream from C2. In contrast, no gene was found within the 175-kb interval between BAT1 and HLA-B, which is relatively devoid of CPG-rich sequences. Bronson et al. (1991) isolated yeast artificial chromosome (YAC) clones carrying the HLA-B and HLA-C (142840) genes. The loci were found to be located about 85 kb apart, each in close association with a CpG island. Gene Function Fleischhauer et al. (1990) demonstrated that a single amino acid difference in the HLA-B molecule is sufficient for the development of alloreactivity in vivo. They reported the case of a 29-year-old man with chronic myelogenous leukemia who received a bone marrow transplant from an unrelated female donor who was serologically HLA identical and compatible in mixed lymphocyte culture. However, they differed with respect to HLA-B44 subtypes B44.1 and B44.2, which were distinguishable by their characteristic band patterns in isoelectric-focusing (IEF) gel electrophoresis. The IEF difference, based on differences in charged amino acids, was found to be due to leucine versus aspartic acid at position 156. Leinders-Zufall et al. (2004) showed that small peptides that serve as ligands for MHC class I molecules function also as sensory stimuli for a subset of vomeronasal sensory neurons located in the basal G-alpha-o- (139311) and V2R receptor (see 605234)-expressing zone of the vomeronasal epithelium. In behaving mice, the same peptides function as individuality signals underlying mate recognition in the context of pregnancy block. MHC peptides constitute a previously unknown family of chemosensory stimuli by which MHC genotypic diversity can influence social behavior. Molecular Genetics ### HLA Bw4 and Bw6 Epitopes Lutz (2014) reviewed HLA Bw4 and Bw6. As a result of transplantation, blood transfusion, or pregnancy, people are immunized and produce antibodies to 'private' epitopes, which are shared by few other HLA allele products, or 'public' epitopes, which are encoded by many HLA alleles. The most prominent public epitopes are Bw4 and Bw6. Either the Bw4 or the Bw6 epitope is expressed by virtually all HLA-B molecules, and Bw4 is also found on a few HLA-A proteins. Parham et al. (2012) reported that Bw4, along with HLA-A3, HLA-A11, HLA-C1, and HLA-C2, is a KIR (e.g., KIR3DL1; 604946) ligand. Habegger de Sorrentino et al. (2013) listed 14 HLA-B alleles and 4 HLA-A alleles expressing Bw4 epitopes. ### Association With Protection From Severe Malaria By means of a large case-controlled study of malaria (see 611162) in West African children, Hill et al. (1991) showed that HLA-Bw53 and the HLA class II haplotype, DRB11302/DQB10501, (see HLA-DRB1, 142857) are independently associated with protection from severe malaria. The antigens listed are common in West Africans but rare in other racial groups. In this population, they account for as great a reduction in disease incidence as the sickle-cell hemoglobin variant. Although the relative strength of the protection is less than that of the sickle-cell variant, the greater frequency of the DQB1 (see HLA-DQB1, 604305) polymorphism makes the net effect on resistance to malaria comparable. The findings support the hypothesis that the extraordinary polymorphism of major histocompatibility complex genes has evolved primarily through natural selection by infectious pathogens. Hill et al. (1992) further investigated the protective association between HLA-B53 and severe malaria by sequencing peptides eluted from this molecule followed by screening of candidate epitopes from pre-erythrocytic-stage antigens of Plasmodium falciparum in biochemical and cellular assays. Among malaria-immune Africans, they found that HLA-B53-restricted cytotoxic T lymphocytes recognized a conserved nonamer peptide from liver-stage-specific antigen-1 (LSA-1), but no HLA-B53-restricted epitopes were identified in other malaria antigens. The findings of this 'reverse immunogenetic' approach indicated a possible molecular basis for this HLA-disease association and supported the candidacy of LSA-1 as a component for a malaria vaccine. ### Association With HIV-1 Disease Progression Carrington et al. (1999) reported that the extended survival of 28 to 40% of HIV-1-infected Caucasian patients who avoided AIDS for 10 or more years (see 609423) could be attributed to their being fully heterozygous at HLA class I loci, to lacking the AIDS-associated alleles B35 and Cw04, or to both. Gao et al. (2001) examined subtypes of HLA-B35 in 5 cohorts and analyzed the relation of structural differences between subtypes to the risk of progression to AIDS. Two subtypes were identified according to peptide-binding specificity: the HLA-B35-PY group, which consists primarily of HLA-B3501 and binds epitopes with proline in position 2 and tyrosine in position 9; and the more broadly reactive HLA-B35-Px group, which also binds epitopes with proline in position 2 but combines several different amino acids (not including tyrosine) in position 9. The influence of HLA-B35 in accelerating progression to AIDS was completely attributable to HLA-B35-Px alleles, some of which differ from HLA-B35-Py alleles by only 1 amino acid residue. Gao et al. (2001) concluded that the previously observed association of HLA-Cw04 with progression to AIDS was due to its linkage disequilibrium with HLA-B35-Px alleles. The fact that the association with B35-Px was observed in both blacks and whites supported the hypothesis that these HLA-B alleles exert an effect on the immune response to HIV-1 infection. Gao et al. (2005) found that HLA-B alleles acted during distinct intervals after HIV infection. HLA-B35-Px and HLA-B57 were associated with rate of progression to 4 outcomes: (1) progression to CD4+ T cells less than 200 (CD4 less than 200), (2) CD4 less than 200 and/or an AIDS-defining illness, (3) an AIDS-defining illness, and (4) death. HLA-B27 (142830.0001), on the other hand, was only associated with the last 3 outcomes. Protection mediated by HLA-B57 occurred early after infection, whereas HLA-B27-mediated protection instead delayed progression to an AIDS-defining illness after the decline in CD4 counts. HLA-B35-Px showed an early susceptibility effect associated with rapid progression from seroconversion to CD4 less than 200. Gao et al. (2005) proposed that the presence of the various HLA-B alleles may lead to different scenarios for viral escape from cytotoxic T-lymphocyte pressure and virus subtypes with different fitnesses. Martin et al. (2002) reported that the activating KIR allele KIR3DS1 (604946), in combination with HLA-B alleles that encode molecules with isoleucine at position 80 (HLA-B Bw4-80Ile), is associated with delayed progression to AIDS in individuals infected with HIV-1 (604946.0001). In the absence of KIR3DS1, the HLA-B Bw4-80Ile allele was not associated with any of the AIDS outcomes measured. By contrast, in the absence of HLA-B Bw4-80Ile alleles, KIR3DS1 was significantly associated with more rapid progression to AIDS. These observations strongly suggested a model involving an epistatic interaction between the 2 loci. The strongest synergistic effect of these loci was on progression to depletion of CD4+ T cells, which suggested that a protective response of NK cells involving KIR3DS1 and its HLA class I ligands begins soon after HIV-1 infection. Kiepiela et al. (2004) performed a comprehensive analysis of class I restricted CD8+ T cell responses against HIV-1, immune control of which depended upon virus-specific CD8+ T cell activity. In 375 HIV-1 infected study subjects from southern Africa, a significantly greater number of CD8+ T cell responses were HLA-B restricted compared to HLA-A (142800) (2.5-fold; P = 0.0033). Kiepiela et al. (2004) showed that variation in viral set point, in absolute CD4 count and, by inference, in rate of disease progression in the cohort, was strongly associated with particular HLA-B but not HLA-A allele expression (P less than 0.0001 and P = 0.91, respectively). Moreover, substantially greater selection pressure was imposed on HIV-1 by HLA-B alleles than by HLA-A (4.4-fold, P = 0.0003). Kiepiela et al. (2004) concluded that their data indicated that the principal focus of HIV-specific activity is at the HLA-B locus. Furthermore, HLA-B gene frequencies in the population are those likely to be most influenced by HIV disease, consistent with the observation that B alleles evolve more rapidly than A alleles. By testing the effects on HIV disease progression and viral load of inhibitory KIR3DL1 subtypes in combination with HLA-B allelic groups, Martin et al. (2007) determined that highly expressed, highly inhibitory KIR3DL1h alleles strongly enhance protection conferred by HLA-Bw4-80Ile alleles, including HLA-B57. Martin et al. (2007) proposed that greater dependency on the expression of specific KIR3DL1-Bw4 receptor-ligand pairs for NK cell inhibition in the resting state results in more pronounced NK cell responses when the inhibition is abrogated in the face of infection. To define host genetic effects on the outcome of a chronic viral infection, The International HIV Controllers Study (2010) performed genomewide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. The International HIV Controllers Study (2010) identified more than 300 genomewide significant SNPs within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, at positions 62, 63, 67, 70, and 97, as well as an independent HLA-C effect, explained the SNP associations and reconciled both protective and risk HLA alleles. The International HIV Controllers Study (2010) concluded that their results implicated the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection. ### Association With Abacavir Hypersensitivity Abacavir is a commonly used nucleoside analog with potent antiviral activity against HIV-1. Approximately 5 to 9% of patients treated with abacavir develop a hypersensitivity reaction characterized by multisystem involvement that can be fatal in rare cases (Mallal et al., 2002; Hetherington et al., 2002). Symptoms usually appear within the first 6 weeks of treatment and include fever, rash, gastrointestinal symptoms, and lethargy or malaise. Symptoms related to the hypersensitivity reaction worsen with continued therapy and improve within 72 hours of discontinuation of abacavir. Rechallenging with abacavir after a hypersensitivity reaction typically results in recurrence of symptoms within hours. Genetic predisposition for this idiosyncratic hypersensitivity syndrome was suggested by its occurrence in a small percentage of abacavir recipients during a short period of drug exposure, and familial occurrence and decreased incidence in individuals of African American origin (Symonds et al., 2002). Consistent with these clinical observations, a strong predictive association of HLA-B5701 (142830.0003) was demonstrated, with further evidence from recombinant haplotype mapping that the susceptibility locus or loci reside specifically with the 57.1 ancestral haplotype, identified by the haplospecific alleles HLA-B5701 and C4A6 (see 120810) and the HLA-DRB10701, HLA-DQ3 combination (Mallal et al., 2002). Martin et al. (2004) reported that the combination of HLA-B5701 and a haplotypic M493T polymorphism of HSP70-HOM (140559) is highly predictive of abacavir hypersensitivity. ### Association With Ankylosing Spondylitis In a study of 15 multiplex families with ankylosing spondylitis (106300), Rubin et al. (1992, 1994) found that 13 of 15 affected females and 46 of 49 affected males were HLA-B27 (142830.0001) positive, as compared with 22 of 43 unaffected females and 16 of 40 unaffected males. The risk of ankylosing spondylitis for homozygotes was placed at 99.5% and for heterozygotes at 43% with a sporadic risk of 0.1%. The B27 haplotype did not consistently segregate with disease in 2 families, but both families still supported linkage to the major histocompatibility complex. Identity-by-descent analyses showed a significant departure from random segregation among affected avuncular (uncle/nephew-niece) and cousin pairs. The presence of HLA-B40 in HLA-B27 positive individuals increased the risk for disease more than 3-fold, confirming previous reports. Disease susceptibility modeling suggested an autosomal dominant pattern of inheritance with penetrance of approximately 20%. In this study, which involved families from Toronto and Newfoundland, B27 alleles were detected by hybridization with sequence-specific oligonucleotide probes after amplification of genomic DNA by PCR. ### Association With Age-Related Macular Degeneration Goverdhan et al. (2005) investigated whether HLA genotypes were associated with age-related macular degeneration (ARMD; see 603075). They genotyped class I HLA-A, -B, and -Cw (see 142840) and class II DRB1 (142857) and DQB1 (604305) in 200 patients with ARMD, as well as in controls. Allele Cw0701 correlated positively with ARMD, whereas alleles B4001 and DRB11301 were negatively associated. These HLA associations were independent of any linkage disequilibrium. Goverdhan et al. (2005) concluded that HLA polymorphisms influenced the development of ARMD and proposed modulation of choroidal immune function as a possible mechanism for this effect. ### Association With Type I Diabetes Nejentsev et al. (2007) used several large type I diabetes data sets to analyze a combined total of 1,729 polymorphisms, and applied statistical methods--recursive partitioning and regression--to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (142800) (risk ratios greater than 1.5; P(combined) = 2.01 x 10(-19) and 2.35 x 10(-13), respectively) in addition to the established associations of the MHC class II genes HLA-DQB1 (604305) and HLA-DRB1 (142857). Nejentsev et al. (2007) suggested that other loci with smaller and/or rarer effects might also be involved, but to find these future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, Nejentsev et al. (2007) concluded that MHC class I-mediated events, principally involving HLA-B39, contribute to the etiology of type I diabetes. ### Association With Chronic Synovitis Chronic synovitis occurs in about 10% of Indian patients with severe hemophilia (HEMA, 306700; HEMB, 306900). Ghosh et al. (2003) reported an association between the development of chronic synovitis in patients with hemophilia and the HLA-B27 allele (142830.0001). Twenty-one (64%) of 33 patients with both disorders had HLA-B27, compared to 23 (5%) of 440 with severe hemophilia without synovitis (odds ratio of 31.6). There were 3 sib pairs with hemophilia in whom only 1 sib had synovitis; all the affected sibs had the HLA-B27 allele, whereas the unaffected sibs did not. Chronic synovitis presented as swelling of the joint with heat and redness and absence of response to treatment with factor concentrate. Ghosh et al. (2003) suggested that patients with HLA-B27 may not be able to easily downregulate inflammatory mediators after bleeding in the joints, leading to chronic synovitis. ### Association With Severe Cutaneous Adverse Reaction Chung et al. (2004) studied 44 patients with carbamazepine-induced Stevens-Johnson syndrome (608579), including 5 with overlapping toxic epidermal necrolysis, in whom the clinical morphology fulfilled Roujeau's diagnostic criteria (Roujeau, 1994). Controls included 101 patients who had been treated with carbamazepine for at least 3 months without adverse reaction and 93 normal individuals. All participants were Han Chinese residing in Taiwan. One hundred percent of the patients who developed Stevens-Johnson syndrome carried the HLA-B1502 allele (142830.0002), while only 3% of the carbamazepine-tolerant individuals and 8.6% of the normal controls carried this allele. When the carbamazepine-tolerant group was used as the control, the presence of HLA-B1502 had a 93.6% positive predictive value for developing carbamazepine-induced Stevens-Johnson syndrome, whereas its absence had a negative prediction value of 100%. To identify genetic markers for allopurinol-induced severe cutaneous adverse reaction (SCAR; 608579), Hung et al. (2005) genotyped 51 patients with allopurinol-SCAR and 228 controls (135 allopurinol-tolerant patients and 93 healthy individuals) for 823 SNPs in genes related to drug metabolism and immune response. All participants were unrelated Han Chinese residing in Taiwan. The HLA-B5801 allele (142830.0004) was present in all 51 of the patients with allopurinol-SCAR, but in only 15% of allopurinol-tolerant controls and 20% of healthy controls (p = 4.7 x 10(-24) and p = 8.1 x 10(-18), respectively). Hung et al. (2005) concluded that the HLA-B5801 allele is an important genetic risk factor for severe cutaneous adverse reactions to allopurinol in the Han Chinese population. ### Association With Drug-Induced Liver Injury Due To Flucloxacillin In a genomewide association study of 51 patients with flucloxacillin-induced liver injury and 282 controls, Daly et al. (2009) found an association with rs2395029 in the HCP5 gene (604676) in the MHC region (p = 8.7 x 10(-33)). The SNP is in complete linkage disequilibrium with HLA-B5701 (142830.0003). Further MHC genotyping of 64 flucloxacillin-tolerant controls confirmed the association with HLA-B5701 (odds ratio of 80.6; p = 9.0 x 10(-19)). The association was replicated in a second cohort of 23 patients. In HLA-B5701 carriers, rs10937275 in the ST6GAL1 (109675) gene on chromosome 3q also showed genomewide significance (odds ratio of 4.1; p = 1.4 x 10(-8)). ### Association With Chronic Thromboembolic Pulmonary Hypertension Without Deep Vein Thrombosis For a discussion of a possible association between variation in the HLA-B gene and chronic thromboembolic pulmonary hypertension (CTEPH) without deep vein thrombosis, see 612862. ### Association with Tuberculosis Using direct sequencing, Salie et al. (2014) typed the HLA class I alleles from 300 South African patients with tuberculosis (TB; see 607948). The patients were recruited from suburban Cape Town, where TB prevalence is high, HIV infection is low, and the population is highly admixed. Salie et al. (2014) also genotyped the Mycobacterium tuberculosis (Mtb) strains in each patient. They found that the Beijing Mtb strain occurred more frequently in individuals with multiple disease episodes and that the HLA-B27 allele lowered the odds of having an additional episode and of developing an infection with another Mtb strain. Salie et al. (2014) showed that various HLA types were associated with strains originating from both the European American and East Asian lineages, suggesting coevolutionary events between host and pathogen. ### Reviews Cooke and Hill (2001) reviewed the genetics of susceptibility to human infectious disease. Association with class I HLA alleles and infectious disease have been demonstrated mainly with HLA-B: B8 with susceptibility to pulmonary tuberculosis, B35 with susceptibility to AIDS, B53 with resistance to severe malaria, and B57 with resistance to AIDS (see Table 3 of Cooke and Hill, 2001). Evolution All Amerindian groups show limited HLA polymorphism which probably reflects the small founder populations that colonized America by overland migration from Asia 11,000 to 40,000 years ago. Belich et al. (1992) found that the nucleotide sequences of HLA-B alleles from 2 culturally and linguistically distinct tribes of Southern Brazil are distinct from those in Caucasian, Oriental, and other populations. By comparison, the HLA-A (142800) and HLA-C alleles are similar. These results and those reported by Watkins et al. (1992) from studies of a tribe in Ecuador showed that a marked evolution of HLA-B occurred after humans first entered South America. New alleles were formed through recombination between preexisting alleles, not by point mutation, giving rise to distinctive diversification of HLA-B in different South American Indian tribes. Segmental exchanges of this type, even if they occur at a lower frequency than point mutations, could be useful in the development of resistance to infectious disease, for example, inasmuch as the probability of an adaptively useful variant is much higher when there is segmental exchange of already structurally valid coding sequence rather than random point mutation. Although most of the human MHC loci are relatively stable, the HLA-B locus appears to be capable of rapid changes, especially in isolated populations. To investigate the mechanisms of HLA-B evolution, McAdam et al. (1994) compared the sequences of 19 HLA-B homologs from chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) to 65 HLA-B sequences. Despite obvious similarities between chimpanzee and human alleles in exon 2, there was little conservation of exon 3 between human and the 2 chimpanzee species. This finding suggested to McAdam et al. (1994) that, unlike all other HLA loci, recombination has characterized the HLA-B locus and its homologs for over 5 million years. By genotyping individuals from 30 distinct populations, Single et al. (2007) detected strong negative correlations between the presence of activating KIR genes and their corresponding HLA ligand groups across populations, particularly for KIR3DS1 (604946) and its putative HLA-B Bw4-80Ile ligands. Weak positive relationships, on the other hand, were found between inhibitory KIR genes and their HLA ligands. A negative correlation was observed between distance from East Africa and the frequency of activating KIR genes and their corresponding ligands. Single et al. (2007) concluded that activating, rather than inhibitory, receptor-ligand pairs show the strongest signature of coevolution between the complex KIR and HLA genetic systems. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan	MAJOR HISTOCOMPATIBILITY COMPLEX, CLASS I, B	c1840547	27,068	omim	https://www.omim.org/entry/142830	2019-09-22T16:40:10	{"omim": ["142830"], "synonyms": ["Alternative titles", "HLA-B HISTOCOMPATIBILITY TYPE"]}
16p13.11 microdeletion syndrome is a recently described syndrome characterized by developmental delay, microcephaly, epilepsy, short stature, facial dysmorphism and behavioral problems. ## Epidemiology It has been clinically and molecularly characterized in fewer than 15 patients. ## Clinical description Facial features include down-slanting palpebral fissures, short nose, low-set ears, wide mouth and thin upper lip. Variable congenital anomalies can also be observed. ## Etiology This syndrome is caused by an interstitial deletion encompassing 16p13.11. The deletions were characterized by comparative genomic hybridization (CGH) microarray and fluorescence in situ hybridization (FISH). The underlying mechanism is non-allelic homologous recombination (NAHR). Microdeletions appear de novo or are inherited from mildly affected or completely normal parents in an autosomal dominant manner, suggesting that the microdeletion has incomplete penetrance and variable expressivity. Two genes within the deleted region, NDE1 (nudE nuclear distribution gene E homolog 1) and NTAN1 (N-terminal asparagine amidase) may contribute to the neuro-cognitive phenotype. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	16p13.11 microdeletion syndrome	c4304596	27,069	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=261236	2021-01-23T19:10:18	{"icd-10": ["Q93.5"], "synonyms": ["Del(16)(p13.11)", "Monosomy 16p13.11"]}
Hypohidrotic ectodermal dysplasia is one of more than 100 types of ectodermal dysplasia. Starting before birth, these disorders result in the abnormal development of ectodermal tissues, particularly the skin, hair, nails, teeth, and sweat glands. Most people with hypohidrotic ectodermal dysplasia have a reduced ability to sweat (hypohidrosis) because they have fewer sweat glands than normal or their sweat glands do not function properly. Sweating is a major way that the body controls its temperature; as sweat evaporates from the skin, it cools the body. Reduced sweating can lead to a dangerously high body temperature (hyperthermia), particularly in hot weather. In some cases, hyperthermia can cause life-threatening health problems. Affected individuals tend to have sparse scalp and body hair (hypotrichosis). The hair is often light-colored, brittle, and slow-growing. Hypohidrotic ectodermal dysplasia is also characterized by several missing teeth (hypodontia) or teeth that are malformed. The teeth that are present erupt from the gums later than usual and are frequently small and pointed. Some people with hypohidrotic ectodermal dysplasia have distinctive facial features, including a prominent forehead, thick lips, and a flattened bridge of the nose. Additional features of this condition can include thin, wrinkled, and dark-colored skin around the eyes; chronic skin problems such as eczema; and a bad-smelling discharge from the nostrils (ozena). Intellectual ability and growth are typically normal in people with hypohidrotic ectodermal dysplasia. ## Frequency Hypohidrotic ectodermal dysplasia is the most common form of ectodermal dysplasia. It is estimated to occur in 1 in 20,000 newborns worldwide. ## Causes Hypohidrotic ectodermal dysplasia is a genetic condition that can result from mutations in one of several genes. These include EDA, EDAR, EDARADD, and WNT10A. EDA gene mutations are the most common cause of the disorder, accounting for more than half of all cases. EDAR, EDARADD, and WNT10A gene mutations each account for a smaller percentage of cases. In about 10 percent of people with hypohidrotic ectodermal dysplasia, the genetic cause is unknown. The EDA, EDAR, and EDARADD genes provide instructions for making proteins that work together during embryonic development. These proteins form part of a signaling pathway that is critical for the interaction between two cell layers, the ectoderm and the mesoderm. In the early embryo, these cell layers form the basis for many of the body's organs and tissues. Ectoderm-mesoderm interactions are essential for the formation of several structures that arise from the ectoderm, including the skin, hair, nails, teeth, and sweat glands. Mutations in the EDA, EDAR, or EDARADD gene prevent normal interactions between the ectoderm and the mesoderm, which impairs the normal development of skin, hair, nails, teeth, and sweat glands. Mutations in any of these three genes lead to the major signs and symptoms of hypohidrotic ectodermal dysplasia described above. The WNT10A gene provides instructions for making a protein that is part of a different signaling pathway known as Wnt signaling. Wnt signaling controls the activity of certain genes and regulates the interactions between cells during embryonic development. Signaling involving the WNT10A protein is critical for the development of ectodermal structures, particularly the teeth. The WNT10A gene mutations that cause hypohidrotic ectodermal dysplasia impair the protein's function, which disrupts the development of teeth and other structures that arise from the ectodermal cell layer. When hypohidrotic ectodermal dysplasia results from WNT10A gene mutations, its features are more variable than when the condition is caused by mutations in the EDA, EDAR, or EDARADD gene. Signs and symptoms range from mild to severe, and mutations in the WNT10A gene are more likely to cause all of the permanent (adult) teeth to be missing. ### Learn more about the genes associated with Hypohidrotic ectodermal dysplasia * EDA * EDAR * EDARADD * WNT10A ## Inheritance Pattern Hypohidrotic ectodermal dysplasia has several different inheritance patterns. Most cases are inherited in an X-linked pattern and are caused by mutations in the EDA gene. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, 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 copies of the X chromosome, one altered copy of the gene in each cell often leads to less severe features of the condition. Signs and symptoms can include a few missing or abnormal teeth, sparse hair, and mild problems with sweat gland function. However, some females with one copy of the mutated gene have more severe features of this disorder. Less commonly, hypohidrotic ectodermal dysplasia has an autosomal dominant or autosomal recessive pattern of inheritance. Mutations in the EDAR, EDARADD, or WNT10A gene can cause either autosomal dominant or autosomal recessive hypohidrotic ectodermal dysplasia. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. Some affected individuals inherit 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 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. Some mutation carriers have mild signs and symptoms of hypohidrotic ectodermal dysplasia, including a somewhat reduced ability to sweat and less severe dental abnormalities. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Hypohidrotic ectodermal dysplasia	c0162359	27,070	medlineplus	https://medlineplus.gov/genetics/condition/hypohidrotic-ectodermal-dysplasia/	2021-01-27T08:25:11	{"gard": ["76", "2048", "2057", "2049", "10427"], "mesh": ["D053358"], "omim": ["305100", "129490", "224900", "614940", "614941"], "synonyms": []}
A complex form of hereditary spastic paraplegia characterized by a spastic paraplegia presenting in adolescence, associated with the additional manifestations of sensorial hearing impairment due to auditory neuropathy and persistent vomiting due to a hiatal or paraesophageal hernia. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Autosomal dominant spastic paraplegia type 29	c1857855	27,071	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=101009	2021-01-23T17:03:26	{"gard": ["9729"], "mesh": ["C536863"], "omim": ["609727"], "umls": ["C1857855"], "icd-10": ["G11.4"], "synonyms": ["SPG29"]}
## Summary ### Clinical characteristics. Townes-Brocks syndrome (TBS) is characterized by the triad of imperforate anus (84%), dysplastic ears (87%; overfolded superior helices and preauricular tags; frequently associated with sensorineural and/or conductive hearing impairment [65%]), and thumb malformations (89%; triphalangeal thumbs, duplication of the thumb [preaxial polydactyly], and rarely hypoplasia of the thumbs). Renal impairment (42%), including end-stage renal disease (ESRD), may occur with or without structural abnormalities (mild malrotation, ectopia, horseshoe kidney, renal hypoplasia, polycystic kidneys, vesicoutereral reflux). Congenital heart disease occurs in 25%. Foot malformations (52%; flat feet, overlapping toes) and genitourinary malformations (36%) are common. Intellectual disability occurs in approximately 10% of individuals. Rare features include iris coloboma, Duane anomaly, Arnold-Chiari malformation type 1, and growth retardation. ### Diagnosis/testing. The diagnosis of TBS is based on clinical findings; identification of a heterozygous SALL1 pathogenic variant on molecular genetic testing establishes the diagnosis if clinical features are inconclusive. ### Management. Treatment of manifestations: Immediate surgical intervention for imperforate anus; early treatment of hearing loss; surgery for severe malformations of the hands; hemodialysis and possibly kidney transplantation for ESRD; surgery or medical treatment by a cardiologist for congenital heart defects. Surveillance: Annual hearing evaluation; regular monitoring of renal function in individuals with and without renal anomalies, even if renal function is normal on initial examination. Agents/circumstances to avoid: Medications that cause renal or otic toxicity. ### Genetic counseling. TBS is inherited in an autosomal dominant manner. The proportion of cases caused by de novo pathogenic variants is estimated at 50%. Each child of an individual with TBS caused by a SALL1 pathogenic variant has a 50% chance of inheriting the pathogenic variant. Prenatal diagnosis for pregnancies at increased risk is possible if the pathogenic variant has been identified in the family. ## Diagnosis ### Suggestive Findings Townes-Brocks syndrome (TBS) should be suspected in individuals with the following major and minor clinical features. Major features * Imperforate anus or anal stenosis in 84% * Dysplastic ears in 87% (overfolded superior helices, microtia) * Typical thumb malformations in 89% (preaxial polydactyly, triphalangeal thumbs, hypoplastic thumbs) without hypoplasia of the radius Minor features * Sensorineural and/or conductive hearing impairment * Foot malformations * Renal impairment with or without renal malformations * Genitourinary malformations * Congenital heart disease Atypical (not suggestive of TBS) * Radius hypoplasia on clinical examination or radiographs * Cleft lip/palate ### Establishing the Diagnosis The diagnosis of TBS is established in a proband with three major features. If only two major features are present, the presence of minor features and the absence of atypical features further support the diagnosis. Identification of a heterozygous SALL1 pathogenic variant on molecular genetic testing (see Table 1) establishes the diagnosis if clinical features are inconclusive. Molecular testing approaches can include single-gene testing, use of a multigene panel, and more comprehensive genomic testing: * Single-gene testing. Sequence analysis of SALL1 is performed first followed by gene-targeted deletion/duplication analysis if no pathogenic variant is found. * A multigene panel that includes SALL1 and other genes of interest may also be considered. The genes included in multigene panels vary by laboratory and are likely to change over time. However, due to the existence of a highly homologous SALL1 pseudogene (SALL1P1), capture-based gene panels may not be the optimal choice. Note: (1) A few individuals with clinical features of TBS have been found to have pathogenic variants in SALL4 [Kohlhase et al 2002; Borozdin et al 2004; Kohlhase, personal communication]. Therefore, in individuals with a diagnosis of TBS and negative SALL1 testing, SALL4 molecular genetic testing should be considered. (2) Molecular genetic testing of SALL4 rather than SALL1 is suggested as the first molecular test if the radius is involved and/or if Duane anomaly is present. See Differential Diagnosis, Okihiro syndrome and SALL4-Related Disorders. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. * More comprehensive genomic testing (when available) including exome sequencing, genome sequencing, and mitochondrial sequencing may be considered if single-gene testing (and/or use of a multigene panel) fails to confirm a diagnosis in an individual with features of TBS. 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 Townes-Brocks Syndrome View in own window Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method SALL1Sequence analysis 3~70% 4 Gene-targeted deletion/duplication analysis 5~5% 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\. Sequence analysis has detected pathogenic variants in more than 100 individuals with Townes-Brocks syndrome [Kohlhase et al 1998, Kohlhase et al 1999, Marlin et al 1999, Blanck et al 2000, Engels et al 2000, Kohlhase 2000, Salerno et al 2000, Surka et al 2001, Devriendt et al 2002, Kohlhase et al 2003, Botzenhart et al 2005, Walter et al 2006, Botzenhart et al 2007]. Sequence analysis in about 70% and deletion/duplication testing in about 5% identify a SALL1 pathogenic variant or deletion in approximately 75% of persons with the classic triad of malformations as described by Kohlhase et al [1999]. 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 gene-targeted microarray designed to detect single-exon deletions or duplications. 6\. Borozdin et al [2006] identified three and Bardakjian et al [2009] and Miller et al [2012] identified two further multiexon/whole-gene deletions. 7\. A SALL1 pathogenic variant has not been found in a number of individuals with the classic TBS phenotype; thus, locus heterogeneity appears likely. ## Clinical Characteristics In the two most recent studies [Botzenhart et al 2005, Botzenhart et al 2007] of 61 persons with novel SALL1 pathogenic variants (not including the most common pathogenic variant, p.Arg276Ter), 84% had anal anomalies, 89% hand anomalies, and 87% ear anomalies; 67% had the characteristic triad. ### Clinical Description * Gastrointestinal. Imperforate anus, anal stenosis, chronic constipation, gastroesophageal reflux [Engels et al 2000] * Dysplastic ears (overfolded superior helices, microtia), congenital sensorineural and/or conductive hearing loss ranging from mild to severe. Hearing loss that is mild may worsen with age (65% of individuals). * Thumb malformations. Preaxial polydactyly, triphalangeal thumbs, and hypoplastic thumbs without hypoplasia of the radius * Lower extremities. Clubfoot, overlapping toes (II and IV over III), syndactyly of toes, missing toes (III) (52% of individuals) [Surka et al 2001, Botzenhart et al 2005, Botzenhart et al 2007] * Kidneys. Renal agenesis, renal hypoplasia, polycystic kidneys; functional impairment with or without structural abnormalities (42% of individuals) [Surka et al 2001, Botzenhart et al 2005, Botzenhart et al 2007] * Genitourinary. Hypospadias, vaginal aplasia with bifid uterus, bifid scrotum, cryptorchidism (36% of individuals) [Surka et al 2001, Botzenhart et al 2005, Botzenhart et al 2007] * Heart. Congenital heart disease in 50% of persons with the common p.Arg276Ter pathogenic variant [Kohlhase et al 2003] and 12%-25% of persons with other SALL1 pathogenic variants [Surka et al 2001, Botzenhart et al 2005, Botzenhart et al 2007]. Defects include atrial septal defect, ventricular septal defect, tetralogy of Fallot, lethal truncus arteriosus, pulmonary valve atresia, and persistent ductus arteriosus [Surka et al 2001]. * Central nervous system * Intellectual disability (~10%) * Behavioral problems, observed in many children with TBS [Kohlhase, unpublished observations] * Arnold-Chiari malformation type I [Kohlhase, unpublished observations] * Cranial nerve palsy (nerves VI and VII) * Duane anomaly. Uni- or bilateral limitation of abduction of the eye associated with retraction of the globe and narrowing of the palpebral fissure on adduction. The abducens nucleus and nerve (cranial nerve VI) are absent and the lateral rectus muscle is innervated by a branch of the oculomotor nerve (cranial nerve III), accounting for the aberrant ocular movements. * Hypoplasia of the dorsal part of corpus callosum * Growth. Postnatal growth retardation. This poorly documented feature has been described in fewer than 6% to 29% of persons reported with TBS in the literature [Surka et al 2001]. The occurrence of postnatal growth retardation among individuals with a confirmed pathogenic variant is not known. Lawrence et al [2013] reported growth hormone deficiency in an individual with TBS, suggesting that this may also be the cause for growth retardation in other individuals with TBS. * Skeletal. Rib anomalies (fused ribs, missing ribs, additional cervical ribs), mild vertebral anomalies (9%). Painful joints have been observed in several adults with TBS [Kohlhase, unpublished observations]. * Eyes. Microphthalmia (rare), iris coloboma, lamellar cataract, chorioretinal coloboma with loss of vision * Face. Hemifacial microsomia [Kohlhase et al 1999, Keegan et al 2001] * Endocrine. Congenital hypothyroidism (rare) [Lawrence et al 2013] ### Genotype-Phenotype Correlations No genotype-phenotype correlations have been made for the majority of pathogenic variants, most of which are private. The most common pathogenic variant and the only pathogenic variant found in more than two families is c.826C>T (p.Arg276Ter), detected in approximately half of simplex cases with TBS (i.e., a single occurrence in a family) and in one familial case to date [Kohlhase et al 2003]. This pathogenic variant is associated with greater frequency (50%) and severity of congenital heart defects than other pathogenic variants. Fifteen of 16 individuals with this pathogenic variant showed the characteristic triad of anal, thumb, and ear malformations (94%), indicating that this pathogenic variant is associated with a more severe phenotype. In general, pathogenic variants within the hot spot region that is towards the 5' end in exon 2 appear to be associated with a more severe outcome than pathogenic variants towards the 3' in exon 2. In addition, the phenotype associated with deletions of SALL1 appears to be milder than that associated with pathogenic variants in the hot spot region, but only five families with larger deletions have been reported to date [Borozdin et al 2006, Bardakjian et al 2009, Miller et al 2012]. ### Penetrance Penetrance appears to be complete, but expressivity is highly variable. ### Anticipation Apparent increased severity in successive generations is likely attributable to ascertainment bias. ### Nomenclature Feichtiger [1943] provided one of the earliest reports of Townes-Brocks syndrome. Townes & Brocks [1972] were the first to report autosomal dominant transmission of the characteristic anomalies. Kurnit et al [1978] used the term REAR syndrome (for renal, ear, anal, and radial malformations). Monteiro de Pina-Neto [1984] was the first to use the term Townes-Brocks syndrome. ### Prevalence The prevalence is unknown, partly because the clinical diagnosis of Townes-Brocks syndrome is often complicated by overlap with VACTERL association, which may lead to an over-ascertainment of TBS prevalence. Martínez-Frías estimated the prevalence at 1:250,000 but did not use stringent diagnostic criteria for TBS [Martínez-Frías et al 1999]. ## Differential Diagnosis The clinical presentation of Townes-Brocks syndrome (TBS) can overlap with Goldenhar syndrome (hemifacial microsomia) [Gabrielli et al 1993, Kohlhase et al 1999, Keegan et al 2001], Okihiro syndrome (but without malformations of the radius) [Borozdin et al 2004], and branchiootorenal syndrome [Engels et al 2000, Albrecht et al 2004]. TBS also overlaps with VACTERL association. Goldenhar syndrome. The majority of individuals with oculo-auriculo-vertebral spectrum phenotypes do not have upper-limb or anal malformations. However, some persons with SALL1 pathogenic variants have hemifacial microsomia. [Gabrielli et al 1993, Johnson et al 1996, Kohlhase et al 1999, Keegan et al 2001]. Therefore, while hemifacial microsomia alone is not suggestive of the presence of a SALL1 pathogenic variant, it may occur in individuals with a SALL1 pathogenic variant in addition to more typical TBS malformations. Okihiro syndrome (Duane-radial ray syndrome) is characterized by Duane anomaly and radial ray defects, and less commonly by hearing loss and renal position anomalies (see SALL4-Related Disorders). * In a few individuals with clinical TBS, causative SALL4 variants were found instead of SALL1 [Kohlhase et al 2002; Borozdin et al 2004; Kohlhase, personal communication]. In those individuals, both SALL1 and SALL4 molecular genetic testing should be considered. * Duane anomaly can also occur with a SALL1 pathogenic variant [Kohlhase et al 1999, Botzenhart et al 2005]. * Because radial aplasia or hypoplasia and thumb aplasia have not been observed in individuals with a SALL1 pathogenic variant [Kohlhase, unpublished data], their presence points toward a SALL4 pathogenic variant, even if all other features suggest TBS. Branchiootorenal (BOR) syndrome. In two families eventually determined to have SALL1 pathogenic variants, no affected individual had the typical triad of thumb, anal, and ear malformations. Instead, the presence of dysplastic ears and renal malformations or impaired renal function in family members initially led to the consideration of BOR syndrome [Engels et al 2000, Albrecht et al 2004]. VACTERL association (OMIM 192350) comprises vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal malformations, and limb defects. VACTERL is therefore an important differential diagnosis for simplex cases (i.e., a single affected individual in a family) with suspected TBS. To date, severe vertebral defects and tracheo-esophageal fistula have not been observed in persons with a SALL1 pathogenic variant [Kohlhase, unpublished data]. Sib and offspring recurrence risks for VACTERL association are estimated at approximately 1%. A review summarizes current information on VACTERL association [Shaw-Smith 2006]. STAR syndrome (OMIM 300707) is characterized by toe syndactyly, telecanthus, anogenital malformations, and renal malformations similar to TBS. Facial features and toe syndactyly distinguish STAR syndrome from TBS. STAR syndrome is caused by mutation of FAM58A and inherited in an X-linked manner with likely lethality in males. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with Townes-Brocks syndrome (TBS), the following evaluations are recommended: * Hearing. Hearing evaluation as soon as the diagnosis of TBS is suspected (see Deafness and Hereditary Hearing Loss Overview) * Kidneys. Renal ultrasound examination and routine laboratory tests for renal function * Heart. Baseline evaluation by a cardiologist including an echocardiogram * Eyes. Ophthalmology examination to evaluate for ocular features of TBS and atypical finding of Duane anomaly. * Other. Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations The following are indicated: * Imperforate anus. Immediate surgical intervention is required. * Hearing loss. Significant impairment requires early treatment, typically with hearing aids (see Deafness and Hereditary Hearing Loss Overview). * Thumb malformations. Severe malformations of the hands may require surgery (e.g., removal of additional thumbs). * Renal. Impaired renal function requires continuous monitoring, hemodialysis, and possibly kidney transplantation. * Heart defects. Congenital heart defects may require surgery or medical treatment by a cardiologist. ### Surveillance Annual hearing evaluation is indicated. Renal function should be regularly monitored in all individuals with and without renal anomalies, even if no impairment of renal function is detected on initial examination. ### Agents/Circumstances to Avoid Medications that cause renal or otic toxicity should be avoided. ### Evaluation of Relatives at Risk It is appropriate to evaluate relatives at risk in order to identify as early as possible those who would benefit from initiation of treatment and preventive measures. * If the pathogenic variant in the family is known, molecular genetic testing can be used to clarify the genetic status of at-risk relatives. * If the pathogenic variant in the family is not known, clinical evaluation for physical features, hearing problems, renal disease, and heart defects can be used to clarify the disease status of at-risk relatives. 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Townes-Brocks Syndrome	c0265246	27,072	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1445/	2021-01-18T20:52:17	{"mesh": ["C536974"], "synonyms": []}
A number sign (#) is used with this entry because hereditary diffuse gastric cancer (HDGC) and lobular breast cancer (LBC) are caused by heterozygous germline mutation in the E-cadherin gene (CDH1; 192090) on chromosome 16q22. Somatic mutation in the CDH1 gene has also been found in patients with sporadic diffuse gastric cancer and lobular breast cancer. Description Hereditary diffuse gastric cancer is an autosomal dominant cancer predisposition syndrome. Heterozygous CDH1 mutation carriers have a 70 to 80% lifetime risk of developing diffuse gastric cancer. In addition to gastric cancer, up to 60% of female mutation carriers develop lobular carcinoma of the breast, and some carriers may develop colorectal cancer. Identification of mutation carriers is important, because the characteristic microscopic foci of signet ring cell adenocarcinoma in HDGC usually involves the submucosa and is often not readily detectable by routine upper endoscopy screening (summary by Fitzgerald et al., 2010). HDGC is considered to be a distinct disease entity from the more common sporadic occurrence of gastric cancer (613659), which can be associated with environmental factors, such as Helicobacter pylori infection, high-fat diet, or smoking, and is often associated with somatic mutations in disease tissue. Clinical Features Jones (1964) described 3 multigenerational Maori families from New Zealand segregating early-onset familial gastric cancer. These families were later studied in detail by Guilford et al. (1998). In 1 family, 25 members ranging in age from 14 years upwards had died over 30 years. The majority of cases occurred before age 40 years, which was in marked contrast to the general experience in New Zealand, where about 80% of gastric cancers occur in people older than 60 years. There was no evidence of an increased cancer rate of other organs in this family. Pathology showed histologically poorly differentiated, high-grade, diffuse gastric cancer. Kakiuchi et al. (1999) studied the clinical features of the probands of 16 Japanese gastric cancer families, which was defined as the existence of 3 or more family members with gastric cancer in at least 2 successive generations. These patients developed cancers more frequently in the cardiac region of the stomach. In addition, the cancers were more often of the undifferentiated type, and were more frequently associated with disseminated peritoneal and liver metastases compared to sporadic cases. Richards et al. (1999) reported a family from the U.K. in which 6 individuals developed diffuse gastric cancer. In addition to the 6 members with gastric cancer, 1 member of the family developed adenocarcinoma of the rectum at the age of 30 years. Genetic analysis identified a heterozygous mutation in the CDH1 gene (192090.0008). Huntsman et al. (2001) described genetic screening, surgical management, and pathologic findings in young persons with truncating CDH1 mutations (192090.0012; 192090.0013) in 2 unrelated families with hereditary diffuse gastric cancer reported by Gayther et al. (1998). Total gastrectomy was performed prophylactically in 5 carriers of mutations who were between 22 and 40 years of age. In each case, superficial infiltrates of malignant signet ring cells were identified in surgical samples. Chun et al. (2001) reported a family with a strong history of HDGC. Five family members, including a sister and brother and 3 first cousins, underwent endoscopic evaluations, which were negative for malignancy, and elected to undergo a prophylactic total gastrectomy with Roux-en-Y esophagojejunostomy. Intramucosal signet ring cell adenocarcinoma was found in various regions of the stomach in all 5 patients, and all 5 demonstrated diminished or absent E-cadherin reactivity in the cancerous mucosa. The age of the 5 patients at the time of surgery varied from 40 to 63 years. Brooks-Wilson et al. (2004) reported 10 different families with hereditary gastric cancer who had germline mutations in the CDH1 gene. There were multiple cases of breast cancers, including pathologically confirmed lobular breast cancer, in these families. In a retrospective study of French patients who underwent genetic testing for germline mutations in the CDH1 gene, Benusiglio et al. (2013) found that 18 (11%) of 165 index cases carried pathogenic mutations. Eleven of these patients had a personal or family history that fulfilled diagnostic criteria delineated by Fitzgerald et al. (2010) (see DIAGNOSIS). However, 7 remaining cases did not meet the HDGC criteria: 3 women had sporadic bilateral lobular breast cancer before age 50; 3 came from families with 2 cases of DGC after age 50; and 1 had sporadic diffuse gastric cancer after age 40. Of the 3 woman with LBC before age 50, 2 were only tested for CDH1 after subsequently developing symptomatic DGC and thus meeting the criteria. The remaining woman had CDH1 testing and prophylactic gastrectomy that revealed DGC despite a negative screening endoscopy. These findings suggested that early-onset LBC might be the first manifestation of HDGC, and that a personal or family history of multiple LBCs at a young age, even in the absence of DGC, should prompt cancer geneticists to test for CDH1 germline mutations. ### Hereditary Diffuse Gastric Cancer with or without Cleft Palate Frebourg et al. (2006) reported 2 unrelated families segregating diffuse gastric cancer and cleft palate. Genetic analysis confirmed that affected individuals with gastric cancer with or without cleft palate had heterozygous mutations in the CDH1 gene (192090.0019 and 192090.0020, respectively). In 1 family, 4 mutation carriers had diffuse gastric cancer and cleft lip/palate and 2 mutation carriers had gastric cancer without clefting. In the second family, a man and his 2 daughters had gastric cancer, a daughter with the mutation had cleft lip but no gastric cancer at age 25, and a 16-year-old son with the mutation had congenital aplasia cutis of the scalp and partial acrania (107600) but no known gastric cancer. Both mutations were splicing mutations generating aberrant transcripts with an in-frame deletion, removing the extracellular cadherin repeat domains involved in cell-cell adhesion. Such transcripts might encode mutant proteins with trans-dominant-negative effects. Expression of CDH1 in human embryos during critical stages of lip and palate development suggested that alteration of the E-cadherin pathway may contribute to human clefting. Diagnosis Caldas et al. (1999) reported the proceedings of the First Workshop of the International Gastric Cancer Linkage Consortium convened to produce consensus statements and guidelines for familial gastric cancer. Caldas et al. (1999) noted that review of pathologic samples from 8 families with inactivating germline mutations in the E-cadherin gene showed that all of the gastric cancers in these families were of diffuse type, and 2 of these had a glandular/intestinal component. Hereditary diffuse gastric cancer was defined as existing in any family in which there were (1) 2 or more documented cases of diffuse gastric cancer in first- or second-degree relatives with at least one cancer diagnosed before the age of 50; or (2) 3 or more cases of diffuse gastric cancer in first- or second-degree relatives independent of age of onset. Caldas et al. (1999) also noted that since 5 individuals below the age of 18 had developed diffuse gastric carcinoma, testing of minors might be justified. Fitzgerald et al. (2010) presented updated consensus guidelines for HDGC, which included broadening of CDH1 testing criteria: histologic confirmation of diffuse gastric criteria is only required for 1 family member; inclusion of individuals with diffuse gastric cancer before the age of 40 years without a family history; and inclusion of individuals and families with diagnoses of both diffuse gastric cancer (including one before the age of 50 years) and lobular breast cancer. Large genomic rearrangements of CDH1 should be sought in addition to direct sequencing. Benusiglio et al. (2013) suggested that the criteria for CDH1 testing put forth by Fitzgerald et al. (2010) may be too strict, and proposed that a personal or family history of 2 histologically proven lobular breast cancers before age 50, after exclusion of a germline mutation in BRCA1 and BRCA2, should be added to the criteria for CDH1 testing. Van der Post et al. (2015) reported the results of a multidisciplinary workshop that discussed genetic testing and management of patients with hereditary diffuse gastric cancer (DGC). The workshop recommended that CDH1 testing criteria should take into account first and second-degree relatives: (1) families with 2 or more patients with gastric cancer at any age, 1 confirmed diffuse gastric cancer; (2) individuals with DGC before the age of 40 and (3) families with diagnoses of both DGC and lobular breast cancer (LBC), 1 diagnosis before the age of 50. Additionally, CDH1 testing could be considered in patients with bilateral or familial LBC before the age of 50, patients with DGC and cleft lip/palate, and those with precursor lesions for signet ring cell carcinoma. Clinical Management Fitzgerald et al. (2010) presented updated consensus guidelines for the genetic counseling, management, and surveillance of HDGC. They recommended strong consideration of prophylactic total gastrectomy in mutation-positive individuals or, at the least, detailed endoscopic surveillance with multiple biopsies. Annual mammography and breast MRI from the age of 35 years was recommended for women. Lynch et al. (2000) described E-cadherin mutation-based genetic counseling in an affected kindred reported by Guilford et al. (1999). Of 24 family members tested for the familial mutation (192090.0011), 9 were found to be positive and 15 negative. None of the 19 patients counseled wanted results sent to their physicians once they recognized the potential for insurance discrimination. None had undergone endoscopic ultrasound. Three who were positive for the mutation expressed strong interest in prophylactic gastrectomy. Three of the 9 who tested positive were affected and had died by the time of report. Van der Post et al. (2015) reported the results of a multidisciplinary workshop that discussed management of patients who test positive for CDH1 pathogenic variants related to diffuse gastric cancer. Given the high mortality associated with invasive disease, prophylactic total gastrectomy at a center of expertise was advised for individuals with pathogenic CDH1 mutations. Breast cancer surveillance with annual breast MRI starting at age 30 for women with a CDH1 mutation was recommended. Standardized endoscopic surveillance in experienced centers was recommended for those opting not to have gastrectomy, those with CDH1 variants of uncertain significance, and those that fulfill hereditary DGC criteria without germline CDH1 mutations. Inheritance Hereditary diffuse gastric cancer is an autosomal dominant cancer predisposition syndrome. Heterozygous CDH1 mutation carriers have a 70 to 80% lifetime risk of developing gastric cancer. In addition to gastric cancer, up to 60% of female mutation carriers will develop lobular carcinoma of the breast, and some carriers may develop colorectal cancer (summary by Fitzgerald et al., 2010). Pathogenesis Lauren (1965) defined 2 main histologic types of gastric carcinomas, a 'diffuse' type and a so-called 'intestinal' type. Diffuse tumors, as observed in HDGC, are poorly differentiated infiltrating lesions resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease. This classification system was updated (Carneiro et al., 1995) to include 4 main types of gastric cancer: isolated cell and mixed types (representing the diffuse component); and glandular/intestinal and solid (representing the non-diffuse component). In a review of HDGC from a consensus statement, Fitzgerald et al. (2010) noted that histologic study of prophylactic gastrectomies almost universally showed pre-invasive lesions, including in situ signet ring carcinoma with pagetoid spread of signet ring cells. Mapping By linkage analysis of a large New Zealand family with autosomal dominant inheritance of diffuse gastric cancer, Guilford et al. (1998) found significant linkage to chromosome 16q22.1 (maximum 2-point lod score of 5.04 at marker D16S752). Segregation of the disease haplotype indicated a penetrance of 70% by age 60 years. Molecular Genetics In affected members of 3 New Zealand families with HDGC, Guilford et al. (1998) identified heterozygous germline mutations in the CDH1 gene (192090.0005-192090.0007). Grady et al. (2000) noted that patients with heterozygous germline mutations in the CDH1 gene develop gastric cancer, but their cancers consistently demonstrate no loss of heterozygosity (LOH) at the CDH1 locus. They hypothesized that methylation of the CDH1 promoter might represent the 'second genetic hit' in the genesis of these tumors. The CDH1 promoter was found to be consistently unmethylated in normal stomach mucosa, whereas 3 of 6 HDGC tumors with negative CDH1 staining had aberrant CDH1 promoter methylation. Two tumors that had retained unmethylated CDH1 promoters harbored somatic CDH1 mutations. No somatic mutations were found in 2 HDGC tumors showing CDH1 promoter methylation, but sequence polymorphisms confirmed that they retained a second wildtype allele. These findings indicated that the formation of HDGC tumors requires biallelic CDH1 inactivation, which in one-half of cases is accomplished by promoter methylation of a retained wildtype allele. In a family with a strong history of diffuse gastric carcinoma, Chun et al. (2001) found a 1558insC germline mutation in the CDH1 gene (192090.0014). Oliveira et al. (2002) performed germline CDH1 mutation screening in 39 kindreds with familial aggregation of gastric cancer, a subset of which fulfilled the criteria defined by the International Gastric Cancer Linkage Consortium (IGCLC) for hereditary diffuse gastric cancer. CDH1 germline mutations were detected in 4 of 11 (36.4%) HDGC families. No mutations were identified in 63.6% of HDGC families or in kindreds with familial aggregation of gastric cancer not fulfilling criteria for HDGC. These results added support to the evidence that only HDGC families harbor germline mutations in CDH1 and that genes other than CDH1 remained to be identified. Among 43 apparent cases of hereditary gastric cancer, Brooks-Wilson et al. (2004) identified heterozygous mutations in the CDH1 gene in 10 different families. There were 10 loss-of-function mutations, including 2 insertions, 5 deletions, 2 splice site substitutions, and 1 complex deletion/insertion involving a splice site. They also found 3 heterozygous missense mutations that were predicted to affect conserved residues and to have deleterious effects on protein function. Oliveira et al. (2009) reported 6 (6.5%) of 93 previously described mutation-negative hereditary diffuse gastric cancer probands who carried genomic deletions of the CDH1 gene (see, e.g., 192090.0022 and 192090.0023). The statistically significant overrepresentation of Alu repeats around breakpoints indicated nonhomologous allelic recombination of Alu repeats as a likely mechanism for these deletions. When all mutations and deletions were considered, the overall frequency of CDH1 alterations in HDGC was approximately 46% (73 of 160), and large CDH1 deletions occurred in 3.8% of HDGC families. Among 18 index patients with germline CDH1 mutations identified retrospectively, Benusiglio et al. (2013) found 16 different mutations, including 14 point mutations and 2 large deletions. Most of the mutations were truncating; 9 of the 16 mutations had not previously been reported. Nomenclature Benusiglio et al. (2013) proposed using the name 'Hereditary Diffuse Gastric and Lobular Breast Cancer' for this disorder instead of HDGC. INHERITANCE \- Autosomal dominant HEAD & NECK Mouth \- Cleft lip (in some patients) \- Cleft palate (in some patients) NEOPLASIA \- Gastric cancer, diffuse type, poorly differentiated, high-grade submucosal lesions \- Signet ring cell adenocarcinoma \- Breast cancer, lobular \- Colorectal cancer (in some patients) MISCELLANEOUS \- Average age at onset 38 years \- Onset in teens has been reported \- Penetrance of 70 to 80% over a lifetime in heterozygous mutation carriers \- Up to 60% of female mutation carriers develop lobular breast cancer MOLECULAR BASIS \- Caused by mutation in the cadherin-1 gene (CDH1, 192090.0002 ) ▲ 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	GASTRIC CANCER, HEREDITARY DIFFUSE	c1708349	27,073	omim	https://www.omim.org/entry/137215	2019-09-22T16:40:50	{"doid": ["10534"], "mesh": ["D013274"], "omim": ["137215"], "orphanet": ["26106"], "synonyms": ["Alternative titles", "GASTRIC CANCER, HEREDITARY DIFFUSE", "GASTRIC CANCER, FAMILIAL DIFFUSE"], "genereviews": ["NBK1139"]}
Alcohol intolerance is characterized by immediate unpleasant reactions after drinking alcohol. The most common signs and symptoms of alcohol intolerance are stuffy nose and skin flushing. Alcohol intolerance is caused by a genetic condition in which the body is unable to break down alcohol efficiently. It is most common in Asians. These individuals accumulate acetaldehyde, the primary metabolite of ethanol, because of a genetic polymorphism that doesn't allow aldehyde dehydrogenase (ALDH) to metabolize acetaldehyde to nontoxic acetate. The only way to prevent alcohol intolerance reactions is to avoid alcohol. Alcohol intolerance isn't an allergy. However, in some cases, what seems to be alcohol intolerance may be a reaction to something in an alcoholic beverage, such as chemicals, grains, or preservatives. Combining alcohol with certain medications also can cause reactions. In rare instances, an unpleasant reaction to alcohol can be a sign of a serious underlying health problem that requires diagnosis and treatment. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Acute alcohol sensitivity	c2674838	27,074	gard	https://rarediseases.info.nih.gov/diseases/12634/acute-alcohol-sensitivity	2021-01-18T18:02:18	{"omim": ["610251"], "synonyms": ["Alcohol intolerance", "Hangover, susceptibility to"]}
Familial atrial fibrillation is a rare, genetically heterogenous cardiac disease characterized by erratic activation of the atria with an irregular ventricular response, in various members of a single family. It may be asymptomatic or associated with palpitations, dyspnea and light-headedness. Concomitant rhythm disorders and cardiomyopathies are frequently reported. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Familial atrial fibrillation	c1837014	27,075	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=334	2021-01-23T19:04:22	{"gard": ["9740"], "mesh": ["C563817"], "omim": ["607554", "608583", "608988", "611493", "611494", "611819", "612201", "612240", "613055", "613120", "613980", "614022", "614049", "614050", "615377", "615378", "615770", "617280"], "icd-10": ["I48.9"]}
This article relies too much on references to primary sources. Please improve this by adding secondary or tertiary sources. (November 2014) (Learn how and when to remove this template message) Brown–Vialetto–Van Laere syndrome Other namesBVVLS1 [1] Brown-Vialetto-Van-Laere syndrome (BVVL), sometimes known as Brown's Syndrome, is a rare degenerative disorder often initially characterized by progressive sensorineural deafness.[2] The syndrome most often affects children, adolescents, and young adults. As knowledge of BVVL grows some adult patients have now been diagnosed. With prompt treatment the prognosis may be positive with some patients stabilizing and even major improvements noted in certain cases. ## Contents * 1 Symptoms * 2 Genetics * 3 Diagnosis * 4 Treatment * 5 Prognosis * 6 Epidemiology * 7 History * 8 See also * 9 References * 10 Further reading * 11 External links ## Symptoms[edit] BVVL is marked by a number of cranial nerve palsies, including those of the motor components involving the 7th and 9th-12th cranial nerves, spinal motor nerves, and upper motor neurons.[2] Major features of BVVL include facial and neck weakness, fasciculation of the tongue, and neurological disorders from the cranial nerves.[3] The neurological manifestations develop insidiously: they usually begin with sensorineural deafness, progress inexorably to paralysis, and often culminate in respiratory failure. Most mortality in patients has been from either respiratory infections or respiratory muscle paralysis. Pathological descriptions of BVVL include injury and depletion of 3rd-7th cranial nerves, loss of the spinal anterior horn cells, degeneration of Purkinje cells, as well as degeneration of the spinocerebellar and pyramidal tracts.[3] The first symptoms in nearly all cases of BVVL is progressive vision loss and deafness, and the first initial symptoms are seen anywhere from one to three years.[4] Most cases of deafness are followed by a latent period that can extend anywhere from weeks to years, and this time is usually marked by cranial nerve degeneration. Neurological symptoms of BVVL include optic atrophy, cerebellar ataxia, retinitis pigmentosa, epilepsy and autonomic dysfunction.[4] Non-neurological symptoms can include diabetes, auditory hallucinations, respiratory difficulties, color blindness, and hypertension.[citation needed] ## Genetics[edit] BVVL has autosomal recessive pattern of inheritance The disorder has been associated with various mutations in the SLC52A2 and SLC52A3 genes.[1][5][6] This gene is thought to be involved in transport of riboflavin.[7] BVVL is allelic and phenotypically similar to Fazio–Londe disease and likewise is inherited in an autosomal recessive manner.[citation needed] ## Diagnosis[edit] Diagnosis requires a neurological examination and neuroimaging can be helpful.[8] BVVL can be differentially diagnosed from similar conditions like Fazio-Londe syndrome and amyotrophic lateral sclerosis, in that those two conditions don't involve sensorineural hearing loss, while BVVL, Madras motor neuron disease, Nathalie syndrome, and Boltshauser syndrome do. Nathalie syndrome does not involve lower cranial nerve symptoms, so it can be excluded if those are present. If there is evidence of lower motor neuron involvement, Boltshauser syndrome can be excluded. Finally, if there is a family history of the condition, then BVVL is more likely than MMND, as MMND tends to be sporadic.[8] Genetic testing is able to identify genetic mutations underlying BVVL.[6] ## Treatment[edit] As of 2017, there were case reports that treatment with high doses of riboflavin 5 phosphate can halt the progress of Brown–Vialetto–Van Laere syndrome and in some cases can improve symptoms.[9][10] The first report of BVVL syndrome in Japanese literature was of a woman that had BVVL and showed improvement after such treatments. The patient was a sixty-year-old woman who had symptoms such as sensorineural deafness, weakness, and atrophy since she was 15 years old. Around the age of 49 the patient was officially diagnosed with BVVL, intubated, and then attached to a respirator to improve her CO2 narcosis. After the treatments, the patient still required respiratory assistance during sleep; however, the patient no longer needed assistance by a respirator during the daytime.[11] ## Prognosis[edit] The clinical course of BVVL can vary from one patient to another. There have been cases with progressive deterioration, deterioration followed by periods of stabilization, and deterioration with abrupt periods of increasing severity.[3] The syndrome has previously been considered to have a high mortality rate but the initial response of most patients to the Riboflavin protocol are very encouraging and seem to indicate a significantly improved life expectancy could be achievable. There are three documented cases of BVVL where the patient died within the first five years of the disease. On the contrary, most patients have survived more than 10 years after the onset of their first symptom, and several cases have survived 20–30 years after the onset of their first symptom.[4] Families with multiple cases of BVVL and, more generally, multiple cases of infantile progressive bulbar palsy can show variability in age of disease onset and survival. Dipti and Childs described such a situation in which a family had five children that had Infantile PBP. In this family, three siblings showed sensorineural deafness and other symptoms of BVVL at an older age. The other two siblings showed symptoms of Fazio-Londe disease and died before the age of two.[12] ## Epidemiology[edit] As of 2015, there are approximately 70 known cases of Brown-Vialetto-Van-Laere syndrome worldwide.[2] BVVL was first described in a Portuguese family, and has since been described in a number of ethnic groups. Reports have shown that BVVL infects females more than males at a rate of 5:1 respectively. However, males usually exhibit more severe symptoms, an earlier onset of deafness and a tendency to die earlier in life.[2] ## History[edit] The syndrome was first described by Charles Brown in 1894;[13] further accounts by Vialetto[14] and Van Laere[15] followed in 1936 and 1966, respectively. There were very few cases reported in the medical literature over the 100 odd years since its first description however with the specific genetic testing available in recent years more cases are being identified and treated.[citation needed] ## See also[edit] * Fazio–Londe disease ## References[edit] 1. ^ a b Online Mendelian Inheritance in Man (OMIM): 211530 2. ^ a b c d Voudris, KA; Skardoutsou, A; Vagiakou, EA (2002). "Infantile progressive bulbar palsy with deafness". Brain & Development. 24 (7): 732–735. doi:10.1016/S0387-7604(02)00085-2. PMID 12427524. S2CID 7690110. 3. ^ a b c Prabhu, HV; Brown, MJ (June 2005). "Brown-Vialetto-Van Laere syndrome: a rare syndrome in otology". The Journal of Laryngology & Otology. 119 (6): 470–2. doi:10.1258/0022215054273179. PMID 15992475. 4. ^ a b c Sathasivam, S; O’Sullivan, S; Nicolson, A; Tilley, PJB; Shaw, PJ (2000). "Brown-Vialetto-Van Laere syndrome: Case report and literature review". Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders. 1 (4): 277–281. doi:10.1080/14660820050515106. PMID 11465021. S2CID 42001695. 5. ^ Green, P; Wiseman, M; Crow, YJ; et al. (March 2010). "Brown-Vialetto-Van Laere syndrome, a ponto-bulbar palsy with deafness, is caused by mutations in c20orf54". American Journal of Human Genetics. 86 (3): 485–9. doi:10.1016/j.ajhg.2010.02.006. PMC 2833371. PMID 20206331. 6. ^ a b Johnson, JO; Gibbs, JR; Van Maldergem, L; Houlden, H; Singleton, AB (October 2010). "Exome sequencing in Brown-Vialetto-van Laere syndrome". American Journal of Human Genetics. 87 (4): 567–9, author reply 569–70. doi:10.1016/j.ajhg.2010.05.021. PMC 2948797. PMID 20920669. 7. ^ Yamamoto, S; Inoue, K; Ohta, K; Fukatsu, R; Maeda, J; Yoshida, Y; Yuasa, H (2009). "Identification and Functional Characterization of Rat Riboflavin Transporter 2". Journal of Biochemistry. 145 (4): 437–443. doi:10.1093/jb/mvn181. PMID 19122205. 8. ^ a b Sathasivam, S (17 April 2008). "Brown-Vialetto-Van Laere syndrome". Orphanet Journal of Rare Diseases. 3: 9. doi:10.1186/1750-1172-3-9. PMC 2346457. PMID 18416855. 9. ^ Allison, T; Roncero, I; Forsyth, R; Coffman, K; Pichon, JL (May 2017). "Brown-Vialetto-Van Laere Syndrome as a Mimic of Neuroimmune Disorders: 3 Cases From the Clinic and Review of the Literature". Journal of Child Neurology. 32 (6): 528–532. doi:10.1177/0883073816689517. PMID 28116953. S2CID 31769793. 10. ^ Bosch, Annet M; Stroek, Kevin; Abeling, Nico G; Waterham, Hans R; IJlst, Lodewijk; Wanders, Ronald JA (2012). "The Brown-Vialetto-Van Laere and Fazio Londe syndrome revisited: natural history, genetics, treatment and future perspectives". Orphanet Journal of Rare Diseases. 7 (1): 83. doi:10.1186/1750-1172-7-83. PMC 3517535. PMID 23107375. 11. ^ Nemoto, H; Konno, S; Nomoto, N; Wakata, N; Kurihara, T (May 2005). "[A case of Brown-Vialetto-van Laere (BVVL) syndrome in Japan]". Rinsho Shinkeigaku. 45 (5): 357–61. PMID 15960172. 12. ^ Dipti, S; Childs, AM; Livingston, JH; Aggarwal, AK; Miller, M; Williams, C; Crow, YJ (September 2005). "Brown-Vialetto-Van Laere syndrome; variability in age at onset and disease progression highlighting the phenotypic overlap with Fazio-Londe disease". Brain & Development. 27 (6): 443–6. doi:10.1016/j.braindev.2004.10.003. PMID 16122634. S2CID 32223440. 13. ^ Brown CH (1894). "Infantile amyotrophic lateral sclerosis of the family type". Journal of Nervous and Mental Disease. 21 (2): 707–716. doi:10.1097/00005053-189411000-00003. S2CID 143353104. 14. ^ Vialetto E (1936). "Contributo alla forma ereditaria della paralisi bulbare progressive". Rivista sperimentale di freniatria e medicina legale delle alienazioni mentali. 40: 1–24. 15. ^ Van Laere, J (August 1966). "Paralysie bulbo-pontine chronique progressive familiale avec surdité. Un cas de syndrome de Klippel-Trenaunay dans la même fratrie – problèmes diagnostiques et génétiques [Familial progressive chronic bulbo-pontine paralysis with deafness. A case of Klippel-Trenaunay syndrome in siblings of the same family. Diagnostic and genetic problems]". Revue neurologique. 115 (2): 289–95. PMID 5969547. ## Further reading[edit] * Brown-Vialetto-Van Laere syndrome at the US National Library of Medicine Medical Subject Headings (MeSH) * Nair, Pratibha (18 July 2006). "Bulbar Palsy, Progressive, with Sensorineural Deafness" (PDF). The Catalogue for Transmission Genetics in Arabs Database, Centre for Arab Genomic Studies. * Wilson, John Eastman (1909). "Diseases affecting the spinal grey-matter". Diseases of the nervous system. Boericke & Runyon. ## External links[edit] Classification D * OMIM: 211530 * MeSH: C537111 * DiseasesDB: 32666 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Brown–Vialetto–Van Laere syndrome	c0796274	27,076	wikipedia	https://en.wikipedia.org/wiki/Brown%E2%80%93Vialetto%E2%80%93Van_Laere_syndrome	2021-01-18T18:57:37	{"mesh": ["C537111"], "wikidata": ["Q4976847"]}
A number sign (#) is used with this entry because the GPAPP type of chondrodysplasia with joint dislocations is caused by homozygous mutation in the IMPAD1 gene (614010) on chromosome 8q12. Clinical Features Vissers et al. (2011) reported 4 individuals with a distinct condition characterized by short stature, chondrodysplasia with brachydactyly, congenital joint dislocations, micrognathia, cleft palate, and facial dysmorphism. Three patients, a German girl and Turkish sisters, were from consanguineous families, and the fourth patient was born to healthy parents from Kerala, India. Nizon et al. (2012) described 2 unrelated Turkish patients with a Catel-Manzke syndrome (616145)-like phenotype, 1 of whom was a male infant originally reported by Kiper et al. (2011), in whom they identified homozygous loss-of-function mutations in the IMPAD1 gene. The patients had severe growth retardation with short and abnormal extremities, cleft palate with micrognathia, and knee hyperlaxity. Radiographs of hands and feet revealed numerous accessory bones with abnormally shaped phalanges and carpal synostosis. Nizon et al. (2012) noted that in contrast to previously reported patients with IMPAD1 mutations who had recurrent joint dislocations, these patients had only knee hyperlaxity. Inheritance Kiper et al. (2011) reported a male infant, born to consanguineous Turkish parents, with classic features of Catel-Manzke syndrome (616145) as well as ligamentous laxity in the knees. Two previously born female sibs of the patient, one of whom died at birth and the other at postnatal day 13, also had features of the syndrome. Consanguinity and possibly affected sibs led the authors to suggest autosomal recessive inheritance. Molecular Genetics In 4 individuals from 3 unrelated families with the GPAPP form of chondrodysplasia with joint contractures, Vissers et al. (2011) identified homozygous mutations in the IMPAD1 gene (614010.0001-614010.0003). The mutations were found in heterozygous state in the parents and were not found in 1,712 control chromosomes. In 2 unrelated Turkish patients with a Catel-Manzke syndrome (616145)-like phenotype and knee joint laxity, 1 of whom was the male infant originally reported by Kiper et al. (2011), Nizon et al. (2012) identified homozygosity for loss-of-function mutations in the IMPAD1 gene (614010.0003 and 614010.0004). INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature Other \- Prenatal growth delay HEAD & NECK Head \- High forehead Face \- Flat face Ears \- Hearing loss Eyes \- Prominent eyes Nose \- Broad nasal root \- Small nose Mouth \- Micrognathia \- Small mouth \- Posterior cleft palate SKELETAL Skull \- Coronal craniosynostosis Spine \- Reduction of the intervertebral spaces Pelvis \- Dysplasia of the hip acetabulum Limbs \- Shortening and deformity of the limbs \- Patellar dislocation \- Limited supination of the elbow \- Genua valga \- Dysplasia of the proximal femoral epiphyses \- Subluxation of the radial heads Hands \- Brachydactyly \- Hitch-hiker appearance of the thumb \- Short metacarpals \- Irregular size of the metacarpal epiphyses \- Supernumerary carpal ossification centers \- Longitudinal splitting of the proximal phalanx of forefinger \- Fusion of the capitate and hamate bones \- Splitting of the first metacarpal in two parts Feet \- Adducted feet \- Short feet \- Short toes \- Lateral deviation of the fifth toe MOLECULAR BASIS \- Caused by mutation in the inositol monophosphatase domain-containing protein 1 gene (IMPAD1, 614010.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	CHONDRODYSPLASIA WITH JOINT DISLOCATIONS, GPAPP TYPE	c3279757	27,077	omim	https://www.omim.org/entry/614078	2019-09-22T15:56:32	{"omim": ["614078"], "orphanet": ["280586"], "synonyms": ["GPAPP DEFICIENCY", "Alternative titles", "gPAPP deficiency"]}
This article is about lung carcinomas. For other lung tumors, see Lung tumor. cancer in the lung Lung cancer Other namesLung carcinoma A chest X-ray showing a tumor in the lung (marked by arrow) SpecialtyOncology Pulmonology SymptomsCoughing (including coughing up blood), weight loss, shortness of breath, chest pains[1] Usual onset~70 years[2] TypesSmall-cell lung carcinoma (SCLC), non-small-cell lung carcinoma (NSCLC)[3] Risk factors * Tobacco smoking * genetic factors * radon gas * asbestos * air pollution[4][5] Diagnostic methodMedical imaging, tissue biopsy[6][7] PreventionNot smoking, avoiding asbestos exposure TreatmentSurgery, chemotherapy, radiotherapy[7] PrognosisFive-year survival rate 19.4% (US)[2] 41.4% (Japan)[8] Frequency3.3 million affected as of 2015[9] Deaths1.7 million (2015)[10] Lung cancer, also known as lung carcinoma,[7] is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung.[11] This growth can spread beyond the lung by the process of metastasis into nearby tissue or other parts of the body.[12] Most cancers that start in the lung, known as primary lung cancers, are carcinomas.[13] The two main types are small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC).[3] The most common symptoms are coughing (including coughing up blood), weight loss, shortness of breath, and chest pains.[1] The vast majority (85%) of cases of lung cancer are due to long-term tobacco smoking.[4] About 10–15% of cases occur in people who have never smoked.[14] These cases are often caused by a combination of genetic factors and exposure to radon gas, asbestos, second-hand smoke, or other forms of air pollution.[4][5][15][16] Lung cancer may be seen on chest radiographs and computed tomography (CT) scans.[7] The diagnosis is confirmed by biopsy which is usually performed by bronchoscopy or CT-guidance.[6][17] Avoidance of risk factors, including smoking and air pollution, is the primary method of prevention.[18] Treatment and long-term outcomes depend on the type of cancer, the stage (degree of spread), and the person's overall health.[7] Most cases are not curable.[3] Common treatments include surgery, chemotherapy, and radiotherapy.[7] NSCLC is sometimes treated with surgery, whereas SCLC usually responds better to chemotherapy and radiotherapy.[19] Worldwide in 2012, lung cancer occurred in 1.8 million people and resulted in 1.6 million deaths.[13] This makes it the most common cause of cancer-related death in men and second most common in women after breast cancer.[20] The most common age at diagnosis is 70 years.[2] In the United States, five-year survival rate is 19.4%,[2] while in Japan it is 41.4%.[8] Outcomes on average are worse in the developing world.[21] ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Smoking * 2.2 Radon gas * 2.3 Asbestos * 2.4 Air pollution * 2.5 Genetics * 2.6 Other causes * 3 Pathogenesis * 4 Diagnosis * 4.1 Classification * 4.1.1 Non-small-cell lung carcinoma * 4.1.2 Small-cell lung carcinoma * 4.1.3 Others * 4.2 Metastasis * 4.3 Staging * 5 Prevention * 5.1 Smoking ban * 5.2 Screening * 5.3 Other prevention strategies * 6 Management * 6.1 Surgery * 6.2 Radiotherapy * 6.3 Chemotherapy * 6.4 Targeted and immunotherapy * 6.5 Bronchoscopy * 6.6 Palliative care * 6.7 Non-invasive interventions * 7 Prognosis * 8 Epidemiology * 8.1 United States * 8.2 United Kingdom * 9 History * 10 Research directions * 11 References * 12 External links ## Signs and symptoms[edit] Signs and symptoms which may suggest lung cancer include:[1] * Respiratory symptoms: coughing, coughing up blood, wheezing, or shortness of breath * Systemic symptoms: weight loss, weakness, fever, or clubbing of the fingernails * Symptoms due to the cancer mass pressing on adjacent structures: chest pain, bone pain, superior vena cava obstruction, or difficulty swallowing If the cancer grows in the airways, it may obstruct airflow, causing breathing difficulties. The obstruction can also lead to accumulation of secretions behind the blockage, and increase the risk of pneumonia.[1] Depending on the type of tumor, paraneoplastic phenomena — symptoms not due to the local presence of cancer — may initially attract attention to the disease.[22] In lung cancer, these phenomena may include hypercalcemia, syndrome of inappropriate antidiuretic hormone (SIADH, abnormally concentrated urine and diluted blood), ectopic ACTH production, or Lambert–Eaton myasthenic syndrome (muscle weakness due to autoantibodies). Tumors in the top of the lung, known as Pancoast tumors, may invade the local part of the sympathetic nervous system, resulting in Horner's syndrome (dropping of the eyelid and a small pupil on that side), as well as damage to the brachial plexus.[1] Many of the symptoms of lung cancer (poor appetite, weight loss, fever, fatigue) are not specific.[6] In many people, the cancer has already spread beyond the original site by the time they have symptoms and seek medical attention.[23] Symptoms that suggest the presence of metastatic disease include weight loss, bone pain, and neurological symptoms (headaches, fainting, convulsions, or limb weakness).[1] Common sites of spread include the brain, bone, adrenal glands, opposite lung, liver, pericardium, and kidneys.[23] About 10% of people with lung cancer do not have symptoms at diagnosis; these cancers are incidentally found on routine chest radiography.[17] ## Causes[edit] Relationship between cigarette consumption per person (blue) and male lung cancer rates (dark yellow) in the US over the century. Risk of death from lung cancer is strongly correlated with smoking Cancer develops after genetic damage to DNA and epigenetic changes. Those changes affect the cell's normal functions, including cell proliferation, programmed cell death (apoptosis), and DNA repair. As more damage accumulates, the risk for cancer increases.[24] ### Smoking[edit] Tobacco smoking is by far the main contributor to lung cancer.[4] Cigarette smoke contains at least 73 known carcinogens,[25] including benzo[a]pyrene,[26] NNK, 1,3-butadiene, and a radioactive isotope of polonium – polonium-210.[25] Across the developed world, 90% of lung cancer deaths in men and 70% of those in women during the year 2000 were attributed to smoking.[27] Smoking accounts for about 85% of lung cancer cases.[7] A 2014 review found that vaping may be a risk factor for lung cancer but less than that of cigarettes.[28] Passive smoking – the inhalation of smoke from another's smoking – is a cause of lung cancer in nonsmokers. A passive smoker can be defined as someone either living or working with a smoker. Studies from the US,[29][30][31] the UK[32] and other European countries[33] have consistently shown a significantly-increased risk among those exposed to passive smoking.[34] Those who live with someone who smokes have a 20–30% increase in risk while those who work in an environment with secondhand smoke have a 16–19% increase in risk.[35] Investigations of sidestream smoke suggest that it is more dangerous than direct smoke.[36] Passive smoking results in roughly 3,400 lung cancer-related deaths each year in the US.[31] Marijuana smoke contains many of the same carcinogens as those found in tobacco smoke,[37] however, the effect of smoking cannabis on lung cancer risk is not clear.[38][39] A 2013 review did not find an increased risk from light to moderate use.[40] A 2014 review found that smoking cannabis doubled the risk of lung cancer, though cannabis is in many countries commonly mixed with tobacco.[41] ### Radon gas[edit] Radon is a colorless and odorless gas generated by the breakdown of radioactive radium, which in turn is the decay product of uranium, found in the Earth's crust. The radiation decay products ionize genetic material, causing mutations that sometimes become cancerous. Radon is the second most-common cause of lung cancer in the US,[42] causing about 21,000 deaths each year.[43] The risk increases 8–16% for every 100 Bq/m³ increase in the radon concentration.[44] Radon gas levels vary by locality and the composition of the underlying soil and rocks. About one in 15 homes in the US have radon levels above the recommended guideline of 4 picocuries per liter (pCi/l) (148 Bq/m³).[45] ### Asbestos[edit] Asbestos can cause a variety of lung diseases such as lung cancer. Tobacco smoking and asbestos both have synergistic effects on the development of lung cancer.[5] In smokers who work with asbestos, the risk of lung cancer is increased 45-fold compared to the general population.[46] Asbestos can also cause cancer of the pleura, called mesothelioma – which actually is different from lung cancer.[47] ### Air pollution[edit] Outdoor air pollutants, especially chemicals released from the burning of fossil fuels, increase the risk of lung cancer.[4] Fine particulates (PM2.5) and sulfate aerosols, which may be released in traffic exhaust fumes, are associated with a slightly-increased risk.[4][48] For nitrogen dioxide, an incremental increase of 10 parts per billion increases the risk of lung cancer by 14%.[49] Outdoor air pollution is estimated to cause 1–2% of lung cancers.[4] Tentative evidence supports an increased risk of lung cancer from indoor air pollution in relation to the burning of wood, charcoal, dung, or crop residue for cooking and heating.[50] Women who are exposed to indoor coal smoke have roughly twice the risk, and many of the by-products of burning biomass are known or suspected carcinogens.[51] This risk affects about 2.4 billion people worldwide,[50] and it is believed to result in 1.5% of lung cancer deaths.[51] ### Genetics[edit] About 8% of lung cancer is caused by inherited factors.[52] In relatives of people that are diagnosed with lung cancer, the risk is doubled, likely due to a combination of genes.[53] Polymorphisms on chromosomes 5, 6, and 15 are known to affect the risk of lung cancer.[54] Single-nucleotide polymorphisms (SNPs) of the genes encoding the nicotinic acetylcholine receptor (nAChR) – CHRNA5, CHRNA3, and CHRNB4 – are of those associated with an increased risk of lung cancer, as well as RGS17 – a gene regulating G-protein signaling.[54] ### Other causes[edit] Numerous other substances, occupations, and environmental exposures have been linked to lung cancer. The International Agency for Research on Cancer (IARC) states that there is some "sufficient evidence" to show that the following are carcinogenic in the lungs:[55] * Some metals (aluminium production, cadmium and cadmium compounds, chromium(VI) compounds, beryllium and beryllium compounds, iron and steel founding, nickel compounds, arsenic and inorganic arsenic compounds, and underground hematite mining) * Some products of combustion (incomplete combustion, coal (indoor emissions from household coal burning), coal gasification, coal-tar pitch, coke production, soot, and diesel engine exhaust) * Ionizing radiation (X-ray and gamma) * Some toxic gases (methyl ether (technical grade), and bis-(chloromethyl) ether, sulfur mustard, MOPP (vincristine-prednisone-nitrogen mustard-procarbazine mixture) and fumes from painting) * Rubber production and crystalline silica dust * There is a small increase in the risk of lung cancer in people affected by systemic sclerosis. ## Pathogenesis[edit] See also: Carcinogenesis Similar to many other cancers, lung cancer is initiated by either the activation of oncogenes or the inactivation of tumor suppressor genes.[56] Carcinogens cause mutations in these genes that induce the development of cancer.[57] Mutations in the K-ras proto-oncogene contribute to roughly 10–30% of lung adenocarcinomas.[58][59] Nearly 4% of non-small-cell lung carcinomas involve an EML4-ALK tyrosine kinase fusion gene.[60] Epigenetic changes such as alteration of DNA methylation, histone tail modification, or microRNA regulation may result in the inactivation of tumor suppressor genes.[61] Importantly, cancer cells develop resistance to oxidative stress, which enables them to withstand and exacerbate inflammatory conditions that inhibit the activity of the immune system against the tumor.[62][63] The epidermal growth factor receptor (EGFR) regulates cell proliferation, apoptosis, angiogenesis, and tumor invasion.[58] Mutations and amplification of EGFR are common in non-small-cell lung carcinoma, and they provide the basis for treatment with EGFR-inhibitors. Her2/neu is affected less frequently.[58] Other genes that are often mutated or amplified include c-MET, NKX2-1, LKB1, PIK3CA, and BRAF.[58] The cell lines of origin are not fully understood.[1] The mechanism may involve the abnormal activation of stem cells. In the proximal airways, stem cells that express keratin 5 are more likely to be affected, typically leading to squamous-cell lung carcinoma. In the middle airways, implicated stem cells include club cells and neuroepithelial cells that express club cell secretory protein. Small-cell lung carcinoma may originate from these cell lines[64] or neuroendocrine cells,[1] and it may express CD44.[64] Metastasis of lung cancer requires transition from epithelial to mesenchymal cell type. This may occur through the activation of signaling pathways such as Akt/GSK3Beta, MEK-ERK, Fas, and Par6.[65] ## Diagnosis[edit] CT scan showing a cancerous tumor in the left lung Primary pulmonary sarcoma in an asymptomatic 72-year-old male. Performing a chest radiograph is one of the first investigative steps if a person reports symptoms that may be suggestive of lung cancer. This may reveal an obvious mass, the widening of the mediastinum (suggestive of spread to lymph nodes there), atelectasis (lung collapse), consolidation (pneumonia), or pleural effusion.[7] CT imaging of the chest may reveal a spiculated mass which is highly suggestive of lung cancer, and is also used to provide more information about the type and extent of disease. Bronchoscopic or CT-guided biopsy is often used to sample the tumor for histopathology.[17] Lung cancer often appears as a solitary pulmonary nodule on a chest radiograph. However, the differential diagnosis is wide. Many other diseases can also give this appearance, including metastatic cancer, hamartomas, and infectious granulomas caused by tuberculosis, histoplasmosis or coccidioidomycosis.[66] Lung cancer can also be an incidental finding, as a solitary pulmonary nodule on a chest radiograph or CT scan done for an unrelated reason.[67] The definitive diagnosis of lung cancer is based on the histological examination of the suspicious tissue[1] in the context of the clinical and radiological features.[6] Clinical practice guidelines recommend frequencies for pulmonary nodule surveillance.[68] CT imaging should not be used for longer or more frequently than indicated, as the extended surveillance exposes people to increased radiation and is costly.[68] ### Classification[edit] Pie chart showing incidences of non-small cell lung cancers as compared to small cell carcinoma shown at right, with fractions of smokers versus non-smokers shown for each type.[69] Age-adjusted incidence of lung cancer by histological type[4] Histological type Incidence per 100,000 per year All types 66.9 Adenocarcinoma 22.1 Squamous-cell carcinoma 14.4 Small-cell carcinoma 9.8 Lung cancers are classified according to histological type.[6] This classification is important for determining both the management and predicting outcomes of the disease. Lung cancers are carcinomas – malignancies that arise from epithelial cells. Lung carcinomas are categorized by the size and appearance of the malignant cells seen by a histopathologist under a microscope. For therapeutic purposes, two broad classes are distinguished: non-small-cell lung carcinoma and small-cell lung carcinoma.[70] #### Non-small-cell lung carcinoma[edit] Micrograph of squamous-cell carcinoma, a type of non-small-cell carcinoma, FNA specimen, Pap stain The three main subtypes of NSCLC are adenocarcinoma, squamous-cell carcinoma, and large-cell carcinoma.[1] Rare subtypes include pulmonary enteric adenocarcinoma.[71] Nearly 40% of lung cancers are adenocarcinoma, which usually comes from peripheral lung tissue.[6] Although most cases of adenocarcinoma are associated with smoking, adenocarcinoma is also the most-common form of lung cancer among people who have smoked fewer than 100 cigarettes in their lifetimes ("never-smokers")[1][72] and ex-smokers with a modest smoking history.[1] A subtype of adenocarcinoma, the bronchioloalveolar carcinoma, is more common in female never-smokers, and may have a better long-term survival.[73] Squamous-cell carcinoma causes about 30% of lung cancers. They typically occur close to large airways. A hollow cavity and associated cell death are commonly found at the center of the tumor.[6] About 10 to 15% of lung cancers are large-cell carcinoma.[74] These are so named because the cancer cells are large, with excess cytoplasm, large nuclei, and conspicuous nucleoli.[6] #### Small-cell lung carcinoma[edit] Small-cell lung carcinoma (microscopic view of a core needle biopsy) In SCLC, the cells contain dense neurosecretory granules (vesicles containing neuroendocrine hormones), which give this tumor an endocrine or paraneoplastic syndrome association.[75] Most cases arise in the larger airways (primary and secondary bronchi).[17] Sixty to seventy percent have extensive disease (which cannot be targeted within a single radiation therapy field) at presentation.[1] #### Others[edit] Four main histological subtypes are recognised, although some cancers may contain a combination of different subtypes,[70] such as adenosquamous carcinoma.[6] Rare subtypes include carcinoid tumors, bronchial gland carcinomas, and sarcomatoid carcinomas.[6] ### Metastasis[edit] Typical Napsin-A and TTF-1 immunostaining in primary lung carcinoma[1] Histological type Napsin-A TTF-1 Squamous-cell carcinoma Negative Negative Adenocarcinoma Positive Positive Small-cell carcinoma Negative Positive The lungs are a common place for the spread of tumors from other parts of the body. Secondary cancers are classified by the site of origin; for example, breast cancer that has been spread to the lung is called metastatic breast cancer. Metastases often have a characteristic round appearance on chest radiograph.[76] Primary lung cancers also most commonly metastasize to the brain, bones, liver, and adrenal glands.[6] Immunostaining of a biopsy usually helps determine the original source.[77] The presence of Napsin-A, TTF-1, CK7, and CK20 help confirm the subtype of lung carcinoma. SCLC that originates from neuroendocrine cells may express CD56, neural cell adhesion molecule, synaptophysin, or chromogranin.[1] ### Staging[edit] See also: Lung cancer staging Lung cancer staging is an assessment of the degree of spread of the cancer from its original source.[78] It is one of the factors affecting both the prognosis and the potential treatment of lung cancer.[1][78] The evaluation of non-small-cell lung carcinoma (NSCLC) staging uses the TNM classification (tumor, node, metastasis). This is based on the size of the primary tumor, lymph node involvement, and distant metastasis.[1] TNM classification in lung cancer[79][80] T: Primary tumor TX Any of: Primary tumor cannot be assessed Tumor cells present in sputum or bronchial washing, but tumor not seen with imaging or bronchoscopy T0 No evidence of primary tumor Tis Carcinoma in situ T1 Tumor size less than or equal to 3 cm across, surrounded by lung or visceral pleura, without invasion proximal to the lobar bronchus T1mi Minimally invasive adenocarcinoma T1a Tumor size less than or equal to 1 cm across T1b Tumor size more than 1 cm but less than or equal to 2 cm across T1c Tumor size more than 2 cm but less than or equal to 3 cm across T2 Any of: Tumor size more than 3 cm but less than or equal to 5 cm across Involvement of the main bronchus but not the carina Invasion of visceral pleura Atelectasis/obstructive pneumonitis extending to the hilum T2a Tumor size more than 3 cm but less than or equal to 4 cm across T2b Tumor size more than 4 cm but less than or equal to 5 cm across T3 Any of: Tumor size more than 5 cm but less than or equal to 7 cm across Invasion into the chest wall, phrenic nerve, or parietal pericardium Separate tumor nodule in the same lobe T4 Any of: Tumor size more than 7 cm Invasion of the diaphragm, mediastinum, heart, great vessels, trachea, carina, recurrent laryngeal nerve, esophagus, or vertebral body Separate tumor nodule in a different lobe of the same lung N: Lymph nodes NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Metastasis to ipsilateral peribronchial and/or hilar lymph nodes N1a Metastasis to a single N1 nodal station N1b Metastasis to two or more N1 nodal stations N2 Metastasis to ipsilateral mediastinal and/or subcarinal lymph nodes N2a1 Metastasis to one N2 nodal station with no involvement of N1 nodes N2a2 Metastasis to one N2 nodal station and at least one N1 nodal station N2b Metastasis to two or more N2 nodal stations N3 Any of: Metastasis to scalene or supraclavicular lymph nodes Metastasis to contralateral hilar or mediastinal lymph nodes M: Metastasis MX Distant metastasis cannot be assessed M0 No distant metastasis M1a Any of: Separate tumor nodule in the other lung Tumor with pleural or pericardial nodules Malignant pleural or pericardial effusion M1b A single metastasis outside the chest M1c Two or more metastases outside the chest Using the TNM descriptors, a group is assigned, ranging from occult cancer, through stages 0, IA (one-A), IB, IIA, IIB, IIIA, IIIB, and IV (four). This stage group assists with the choice of treatment and estimation of prognosis.[81] Stage group according to TNM classification in lung cancer[1] TNM Stage group T1a–T1b N0 M0 IA T2a N0 M0 IB T1a–T2a N1 M0 IIA T2b N0 M0 T2b N1 M0 IIB T3 N0 M0 T1a–T3 N2 M0 IIIA T3 N1 M0 T4 N0–N1 M0 N3 M0 IIIB T4 N2 M0 M1 IV SCLC has traditionally been classified as "limited stage" (confined to one-half of the chest and within the scope of a single tolerable radiotherapy field) or "extensive stage" (more widespread disease).[1] However, the TNM classification and grouping are useful in estimating prognosis.[81] For both NSCLC and SCLC, the two general types of staging evaluations are clinical staging and surgical staging. Clinical staging is performed before definitive surgery. It is based on the results of imaging studies (such as CT scans and PET scans) and biopsy results. Surgical staging is evaluated either during or after the operation. It is based on the combined results of surgical and clinical findings, including surgical sampling of thoracic lymph nodes.[6] * Diagrams of main features of staging * Stage IA and IB lung cancer * Stage IIA lung cancer * Stage IIB lung cancer * One option for stage IIB lung cancer, with T2b; but if tumor is within 2 cm of the carina, this is stage 3 * Stage IIIA lung cancer * Stage IIIA lung cancer, if there is one feature from the list on each side * Stage IIIA lung cancer * Stage IIIB lung cancer * Stage IIIB lung cancer * Stage IV lung cancer ## Prevention[edit] Cross section of a human lung: The white area in the upper lobe is cancer; the black areas are discoloration due to smoking. Smoking prevention and smoking cessation are effective ways of preventing the development of lung cancer.[82] ### Smoking ban[edit] See also: Smoking ban While in most countries industrial and domestic carcinogens have been identified and banned, tobacco smoking is still widespread. Eliminating tobacco smoking is a primary goal in the prevention of lung cancer, and smoking cessation is an important preventive tool in this process.[83] Policy interventions to decrease passive smoking in public areas such as restaurants and workplaces have become more common in many Western countries.[84] Bhutan has had a complete smoking ban since 2005[85] while India introduced a ban on smoking in public in October 2008.[86] The World Health Organization has called for governments to institute a total ban on tobacco advertising to prevent young people from taking up smoking.[87] They assess that such bans have reduced tobacco consumption by 16% where instituted.[87] ### Screening[edit] Main article: Lung cancer screening Cancer screening uses medical tests to detect disease in large groups of people who have no symptoms.[88] For individuals with high risk of developing lung cancer, computed tomography (CT) screening can detect cancer and give a person options to respond to it in a way that prolongs life.[68][89] This form of screening reduces the chance of death from lung cancer by an absolute amount of 0.3% (relative amount of 20%).[90][91] High risk people are those age 55–74 who have smoked equivalent amount of a pack of cigarettes daily for 30 years including time within the past 15 years.[68] CT screening is associated with a high rate of falsely positive tests which may result in unneeded treatment.[92] For each accurate positive scan there are about 19 false positive scans.[91] Other concerns include radiation exposure[92] and the cost of testing along with follow up.[68] Research has not found two other available tests—sputum cytology or chest radiograph (CXR) screening tests—to have any benefit.[89][93] The United States Preventive Services Task Force (USPSTF) recommends yearly screening using low-dose computed tomography in those who have a total smoking history of 30 pack-years and are between 55 and 80 years old until a person has not been smoking for more than 15 years.[94] Screening should not be done in those with other health problems that would make treatment of lung cancer if found not an option.[94] The English National Health Service was in 2014 re-examining the evidence for screening.[95] ### Other prevention strategies[edit] The long-term use of supplemental vitamin A,[96][97] vitamin C,[96] vitamin D[98] or vitamin E[96] does not reduce the risk of lung cancer. Some studies have found vitamin A, B, and E may increase the risk of lung cancer in those who have a history of smoking.[99] Some studies suggest that people who eat diets with a higher proportion of vegetables and fruit tend to have a lower risk,[31][100] but this may be due to confounding—with the lower risk actually due to the association of a high fruit and vegetables diet with less smoking.[101] Several rigorous studies have not demonstrated a clear association between diet and lung cancer risk,[1][100] although meta-analysis that accounts for smoking status may show benefit from a healthy diet.[102] ## Management[edit] Main article: Treatment of lung cancer Treatment for lung cancer depends on the cancer's specific cell type, how far it has spread, and the person's performance status. Common treatments include palliative care,[103] surgery, chemotherapy, and radiation therapy.[1] Targeted therapy of lung cancer is growing in importance for advanced lung cancer.[104] People who have lung cancer should be encouraged to stop smoking.[105] There is no clear evidence which smoking cessation program is most effective for people who have been diagnosed with lung cancer.[105] It is unclear if exercise training is beneficial for people who have advanced lung cancer.[106] Exercise training may benefit people with NSCLC who are recovering from lung surgery.[107] In addition, exercise training can benefit people with NSCLC who have received radiotherapy, chemotherapy, chemoradiotherapy, or palliative care.[108] Exercise training before lung cancer surgery improves outcomes.[109] A home-based component in rehabilitation is also useful.[108] Even though it is uncertain if home-based prehabilitation leads to less adverse events or hospitalization time, rehabilitation with a home-based component may improve recovery after treatment and overall lung health.[108] ### Surgery[edit] Main article: Lung cancer surgery Pneumonectomy specimen containing a squamous-cell carcinoma, seen as a white area near the bronchi If investigations confirm NSCLC, the stage is assessed to determine whether the disease is localized and amenable to surgery or if it has spread to the point where it cannot be cured surgically. CT scan and positron emission tomography (PET-CT), non-invasive tests, can be used to help rule out malignancy or mediastinal lymph node involvement.[1][110] If mediastinal lymph node involvement is suspected using PET-CT, the nodes should be sampled (using a biopsy) to assist staging, a PET-CT scan is not accurate enough to be used alone.[110] Techniques used for obtaining a sample include transthoracic needle aspiration, transbronchial needle aspiration (with or without endobronchial ultrasound), endoscopic ultrasound with needle aspiration, mediastinoscopy, and thoracoscopy.[111] Blood tests and pulmonary function testing are used to assess whether a person is well enough for surgery.[17] If pulmonary function tests reveal poor respiratory reserve, surgery may not be possible.[1] In most cases of early-stage NSCLC, removal of a lobe of lung (lobectomy) is the surgical treatment of choice. In people who are unfit for a full lobectomy, a smaller sublobar excision (wedge resection) may be performed. However, wedge resection has a higher risk of recurrence than lobectomy. Radioactive iodine brachytherapy at the margins of wedge excision may reduce the risk of recurrence. Rarely, removal of a whole lung (pneumonectomy) is performed.[112] Video-assisted thoracoscopic surgery (VATS) and VATS lobectomy use a minimally invasive approach to lung cancer surgery.[113] VATS lobectomy is equally effective compared to conventional open lobectomy, with less postoperative illness.[114] In SCLC, chemotherapy and/or radiotherapy is typically used.[115] However the role of surgery in SCLC is being reconsidered. Surgery might improve outcomes when added to chemotherapy and radiation in early stage SCLC.[116] The effectiveness of lung cancer surgery (resection) for people with stage I - IIA NSCLC is not clear, however, weak evidence suggests that a combined approach of lung cancer resection and removing the mediastinal lymph nodes (mediastinal lymph node dissection) may improve survival compared to lung resection and a sample of mediastinal nodes (not a complete node dissection).[117] ### Radiotherapy[edit] Internal radiotherapy for lung cancer given via the airway. Radiotherapy is often given together with chemotherapy, and may be used with curative intent in people with NSCLC who are not eligible for surgery.[118] This form of high-intensity radiotherapy is called radical radiotherapy.[119] A refinement of this technique is continuous hyperfractionated accelerated radiotherapy (CHART), in which a high dose of radiotherapy is given in a short time period.[120] Radiosurgery refers to the radiotherapy technique of giving a precise high-dose of radiotherapy that is guided by a computer.[121] Postoperative (adjuvant) thoracic radiotherapy generally should not be used after curative-intent surgery for NSCLC.[122] Some people with mediastinal N2 lymph node involvement might benefit from post-operative radiotherapy.[123] For potentially curable SCLC cases, chest radiotherapy is often recommended in addition to chemotherapy.[6] The ideal timing of these therapies (the optimal time to give radiotherapy and chemotherapy for improving survival) is not known.[124] If cancer growth blocks a short section of bronchus, brachytherapy (localized radiotherapy) may be given directly inside the airway to open the passage. Compared to external beam radiotherapy, brachytherapy allows a reduction in treatment time and reduced radiation exposure to healthcare staff.[125] Evidence for brachytherapy, however, is less than that for external beam radiotherapy.[126] Prophylactic cranial irradiation (PCI) is a type of radiotherapy to the brain, used to reduce the risk of metastasis.[127] PCI is most useful in SCLC. In limited-stage disease, PCI increases three-year survival from 15% to 20%; in extensive disease, one-year survival increases from 13% to 27%.[128] For people who have NSCLC and a single brain metastasis, it is not clear if surgery is more effective than radiosurgery.[121] Recent improvements in targeting and imaging have led to the development of stereotactic radiation in the treatment of early-stage lung cancer. In this form of radiotherapy, high doses are delivered over a number of sessions using stereotactic targeting techniques. Its use is primarily in patients who are not surgical candidates due to medical comorbidities.[129] For both NSCLC and SCLC patients, smaller doses of radiation to the chest may be used for symptom control (palliative radiotherapy).[130][131] The use of higher doses of radiotherapy for palliative care are not shown to prolong survival.[131] ### Chemotherapy[edit] The chemotherapy regimen depends on the tumor type.[6] SCLC, even relatively early stage disease, is treated primarily with chemotherapy and radiation.[132] In SCLC, cisplatin and etoposide are most commonly used.[133] Combinations with carboplatin, gemcitabine, paclitaxel, vinorelbine, topotecan, and irinotecan are also used.[134][135] In advanced NSCLC, chemotherapy improves survival and is used as first-line treatment, provided the person is well enough for the treatment.[136] Typically, two drugs are used, of which one is often platinum-based (either cisplatin or carboplatin). Other commonly used drugs are gemcitabine, paclitaxel, docetaxel,[137][138] pemetrexed,[139] etoposide or vinorelbine.[138] Platinum-based drugs and combinations that include platinum therapy do not appear to be more beneficial for prolonging survival compared to other non-platinum medications, and may lead to a higher risk of serious adverse effects such as nausea, vomiting, anaemia, and thrombocytopenia,[140] especially in people over the age of 70 years.[141] There is not enough evidence to determine which chemotherapy approach is associated with the highest quality of life.[140] There is also insufficient evidence to determine if treating people with NSCLC a second time when the first round of chemotherapy was not successful (second-line chemotherapy) causes more benefit or harm.[142] Adjuvant chemotherapy refers to the use of chemotherapy after apparently curative surgery to improve the outcome. In NSCLC, samples are taken of nearby lymph nodes during surgery to assist staging. If stage II or III disease is confirmed, adjuvant chemotherapy (including or not including postoperative radiotherapy) improves survival by 4% at five years.[143][144][145] The combination of vinorelbine and cisplatin is more effective than older regimens.[144] Adjuvant chemotherapy for people with stage IB cancer is controversial, as clinical trials have not clearly demonstrated a survival benefit.[146] Chemotherapy before surgery in NSCLC that can be removed surgically may improve outcomes.[147][148] Chemotherapy may be combined with palliative care in the treatment of the NSCLC.[149] In advanced cases, appropriate chemotherapy improves average survival over supportive care alone, as well as improving quality of life.[150][149] With adequate physical fitness maintaining chemotherapy during lung cancer palliation offers 1.5 to 3 months of prolongation of survival, symptomatic relief, and an improvement in quality of life, with better results seen with modern agents.[151][152] The NSCLC Meta-Analyses Collaborative Group recommends if the recipient wants and can tolerate treatment, then chemotherapy should be considered in advanced NSCLC.[136][153] ### Targeted and immunotherapy[edit] Several drugs that target molecular pathways in lung cancer are available, especially for the treatment of advanced disease. Erlotinib, gefitinib and afatinib inhibit tyrosine kinase at the epidermal growth factor receptor (EGFR). These EGFR inhibitors may help delay the spread of cancer cells for people with EGFR M+ lung cancer and may improve a person's quality of life.[154] EGFR inhibitors have not been shown to help people survive longer.[154] For people with EGFR mutations, treatment with gefitinib may result in an improved quality of life compared to treatment with chemotherapy.[155] Denosumab is a monoclonal antibody directed against receptor activator of nuclear factor kappa-B ligand and may be useful in the treatment of bone metastases.[156] Monoclonal antibodies used in the treatment of non small cell lung cancer and their mechanism of action. https://doi.org/10.3390/ph13110373 Immunotherapy may be used for both SCLC and NSCLC.[157][158] Non-small cell lung cancer (NSCLC) cells expressing programmed death-ligand 1 (PD-L1) could interact with programmed death receptor 1 (PD-1) expressed on the surface of T cells, and result in decreased tumor cell kill by the immune system.[159] Atezolizumab is an anti PD-L1 monoclonal antibody. Nivolumab and Pembrolizumab are anti PD-1 monoclonal antibodies. Ipilimumab is a monoclonal antibody that targets Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) on the surface of T cells. Bevacizumab is a monoclonal antibody that targets Vascular Endothelial Growth Factor (VEGF) in the circulation and functions as an angiogenesis inhibitor.[159] Multiple phase 3 clinical trials utilizing immunotherapy in the first line for treatment of NSCLC were published, including Pembrolizumab in KEYNOTE-024, KEYNOTE-042, KEYNOTE-189 and KEYNOTE-407; Nivolumab and Ipilimumab in CHECKMATE-227 and CHECKMATE 9LA; and Atezolizumab in IMpower110, IMpower130 and IMpower150.[159] The main treatment arms of phase 3 clinical trials providing immunotherapy in the first line for patients with non-small cell lung cancer. https://doi.org/10.3390/ph13110373 Vaccine-based immunotherapy treatment after surgery or radiotherapy may not lead to improved survival for people with Stage I-III NSCLC.[160] ### Bronchoscopy[edit] Several treatments can be provided via bronchoscopy for the management of airway obstruction or bleeding. If an airway becomes obstructed by cancer growth, options include rigid bronchoscopy, balloon bronchoplasty, stenting, and microdebridement.[161] Laser photosection involves the delivery of laser light inside the airway via a bronchoscope to remove the obstructing tumor.[162] ### Palliative care[edit] Palliative care when added to usual cancer care benefits people even when they are still receiving chemotherapy.[163] These approaches allow additional discussion of treatment options and provide opportunities to arrive at well-considered decisions.[164][165] Palliative care may avoid unhelpful but expensive care not only at the end of life, but also throughout the course of the illness. For individuals who have more advanced disease, hospice care may also be appropriate.[17][165] ### Non-invasive interventions[edit] There is weak evidence to suggest that supportive care interventions (non-invasive interventions) that focus on well-being for people with lung cancer may improve quality of life.[166] Interventions such as nurse follow-ups, psychotherapy, psychosocial therapy, and educational programs may be beneficial, however, the evidence is not strong (further research is needed).[166] Counseling may help people cope with emotional symptoms related to lung cancer.[166] Reflexology may be effective in the short-term, however more research is needed.[166] There is no evidence to suggest that nutritional interventions or exercise programs result in an improvement in the quality of life for a person with lung cancer.[166] ## Prognosis[edit] Outcomes in lung cancer according to clinical stage[81] Clinical stage Five-year survival (%) Non-small-cell lung carcinoma Small-cell lung carcinoma IA 50 38 IB 47 21 IIA 36 38 IIB 26 18 IIIA 19 13 IIIB 7 9 IV 2 1 Of all people with lung cancer in the US, 16.8% survive for at least five years after diagnosis.[2][167] In England and Wales, between 2010 and 2011, overall five-year survival for lung cancer was estimated at 9.5%.[168] Outcomes are generally worse in the developing world.[21] Stage is often advanced at the time of diagnosis. At presentation, 30–40% of cases of NSCLC are stage IV, and 60% of SCLC are stage IV.[6] Survival for lung cancer falls as the stage at diagnosis becomes more advanced: the English data suggest that around 70% of patients survive at least a year when diagnosed at the earliest stage, but this falls to just 14% for those diagnosed with the most advanced disease (stage IV).[169] Prognostic factors in NSCLC include presence of pulmonary symptoms, large tumor size (>3 cm), non-squamous cell type (histology), degree of spread (stage) and metastases to multiple lymph nodes, and vascular invasion. For people with inoperable disease, outcomes are worse in those with poor performance status and weight loss of more than 10%.[170] Prognostic factors in small cell lung cancer include performance status, biological sex, stage of disease, and involvement of the central nervous system or liver at the time of diagnosis.[171] Overall survival in non-small cell lung cancer patients treated with protocols incorporating immunotherapy in the first line for advanced or metastatic disease. Nasser NJ, Gorenberg M, Agbarya A. Pharmaceuticals 2020, 13(11), 373; https://doi.org/10.3390/ph13110373 For NSCLC, the best prognosis is achieved with complete surgical resection of stage IA disease, with up to 70% five-year survival.[172] People with extensive-stage SCLC have an average five-year survival rate of less than 1%. The average survival time for limited-stage disease is 20 months, with a five-year survival rate of 20%.[7] The prognosis of patients with non small cell lung cancer improved significantly in the last years with the introduction of immunotherapy.[159] Patients with tumor PDL-1 expressed over half or more of the tumor cells achieved a median overall survival of 30 months with pembrolizumab. [173] Multiple phase 3 trials providing immunotherapy in the first line for patients with non-small cell lung cancer have been published.[159] According to data provided by the National Cancer Institute, the median age at diagnosis of lung cancer in the US is 70 years,[174] and the median age at death is 72 years.[175] In the US, people with medical insurance are more likely to have a better outcome.[176] ## Epidemiology[edit] Trachea, bronchus, and lung cancers deaths per million person in 2012 0–7 8–12 13–32 33–53 54–81 82–125 126–286 287–398 399–527 528–889 Lung cancer distribution for white males in the United States Lung cancer, incidence, mortality and survival, England 1971–2011 Worldwide, lung cancer is the most-common cancer among men in terms of both incidence and mortality, and among women has the third-highest incidence, and is second after breast cancer in mortality. In 2012, there were 1.82 million new cases worldwide, and 1.56 million deaths due to lung cancer, representing 19.4% of all deaths from cancer.[20] The highest rates are in North America, Europe, and East Asia, with over a third of new cases in China that year. Rates in Africa and South Asia are much lower.[177] The population segment that is most likely to develop lung cancer is people aged over 50 who have a history of smoking. Unlike the mortality rate in men – which began declining more than 20 years ago, women's lung cancer mortality rates have risen over the last decades, and are just recently beginning to stabilize.[178] In the US, the lifetime risk of developing lung cancer is 8% in men and 6% in women.[1] For every 3–4 million cigarettes smoked, one lung cancer death can occur.[179] The influence of "Big Tobacco" plays a significant role in smoking.[180] Young nonsmokers who see tobacco advertisements are more likely to smoke.[181] The role of passive smoking is increasingly being recognized as a risk factor for lung cancer,[34] resulting in policy interventions to decrease the undesired exposure of nonsmokers to others' tobacco smoke.[182] From the 1960s, the rates of lung adenocarcinoma started to rise in relation to other kinds of lung cancer, partially due to the introduction of filter cigarettes. The use of filters removes larger particles from tobacco smoke, thus reducing deposition in larger airways. However, the smoker has to inhale more deeply to receive the same amount of nicotine, increasing particle deposition in small airways where adenocarcinoma tends to arise.[183] Rates of lung adenocarcinoma continues to rise.[184] ### United States[edit] In the US, both black men and black women have a higher incidence.[185] Lung cancer rates are currently lower in developing countries.[186] With increased smoking in developing countries, the rates are expected to increase in the next few years, notably in both China[187] and India.[188] Also in the US, military veterans have a 25–50% higher rate of lung cancer primarily due to higher rates of smoking.[189] During World War II and the Korean War, asbestos also played a role, and Agent Orange may have caused some problems during the Vietnam War.[190] ### United Kingdom[edit] Lung cancer is the third most-common cancer in the UK (around 46,400 people were diagnosed with the disease in 2014),[191] and it is the most common cause of cancer-related death (around 35,900 people died in 2014).[192] ## History[edit] See also: Timeline of lung cancer Lung cancer was uncommon before the advent of cigarette smoking; it was not even recognized as a distinct disease until 1761.[193] Different aspects of lung cancer were described further in 1810.[194] Malignant lung tumors made up only 1% of all cancers seen at autopsy in 1878, but had risen to 10–15% by the early 1900s.[195] Case reports in the medical literature numbered only 374 worldwide in 1912,[196] but a review of autopsies showed the incidence of lung cancer had increased from 0.3% in 1852 to 5.66% in 1952.[197] In Germany in 1929, physician Fritz Lickint recognized the link between smoking and lung cancer,[195] which led to an aggressive antismoking campaign.[198] The British Doctors' Study, published in the 1950s, was the first solid epidemiological evidence of the link between lung cancer and smoking.[199] As a result, in 1964 the Surgeon General of the United States recommended smokers should stop smoking.[200] The connection with radon gas was first recognized among miners in the Ore Mountains near Schneeberg, Saxony. Silver has been mined there since 1470, and these mines are rich in uranium, with its accompanying radium and radon gas.[201] Miners developed a disproportionate amount of lung disease, eventually recognized as lung cancer in the 1870s.[202] Despite this discovery, mining continued into the 1950s, due to the USSR's demand for uranium.[201] Radon was confirmed as a cause of lung cancer in the 1960s.[203] The first successful pneumonectomy for lung cancer was performed in 1933.[204] Palliative radiotherapy has been used since the 1940s.[205] Radical radiotherapy, initially used in the 1950s, was an attempt to use larger radiation doses in patients with relatively early-stage lung cancer, but who were otherwise unfit for surgery.[206] In 1997, CHART was seen as an improvement over conventional radical radiotherapy.[207] With SCLC, initial attempts in the 1960s at surgical resection[208] and radical radiotherapy[209] were unsuccessful. In the 1970s, successful chemotherapy regimens were developed.[210] ## Research directions[edit] Current research directions for lung cancer treatment include immunotherapy,[211][212] which encourages the body's immune system to attack the tumor cells, epigenetics, and new combinations of chemotherapy and radiotherapy, both on their own and together. Many of these new treatments work through immune checkpoint blockade, disrupting cancer's ability to evade the immune system.[211][212] Ipilimumab blocks signaling through a receptor on T cells known as CTLA-4 which dampens down the immune system. It has been approved by the US Food and Drug Administration (FDA) for treatment of melanoma and is undergoing clinical trials for both NSCLC and SCLC.[211] Other immunotherapy treatments interfere with the binding of programmed cell death 1 (PD-1) protein with its ligand PD-1 ligand 1 (PD-L1), and have been approved as first- and subsequent-line treatments for various subsets of lung cancers.[212] Signaling through PD-1 inactivates T cells. Some cancer cells appear to exploit this by expressing PD-L1 in order to switch off T cells that might recognise them as a threat. Monoclonal antibodies targeting both PD-1 and PD-L1, such as pembrolizumab, nivolumab,[65] atezolizumab, and durvalumab[212] are currently in clinical trials for treatment for lung cancer.[211][212] Epigenetics is the study of small, usually heritable, molecular modifications—or "tags"—that bind to DNA and modify gene expression levels. Targeting these tags with drugs can kill cancer cells. Early-stage research in NSCLC using drugs aimed at epigenetic modifications shows that blocking more than one of these tags can kill cancer cells with fewer side effects.[213] Studies also show that giving patients these drugs before standard treatment can improve its effectiveness. Clinical trials are underway to evaluate how well these drugs kill lung cancer cells in humans.[213] Several drugs that target epigenetic mechanisms are in development. Histone deacetylase inhibitors in development include valproic acid, vorinostat, belinostat, panobinostat, entinostat, and romidepsin. DNA methyltransferase inhibitors in development include decitabine, azacytidine, and hydralazine.[61] The TRACERx project is looking at how NSCLC develops and evolves, and how these tumors become resistant to treatment.[214] The project will look at tumor samples from 850 NSCLC patients at various stages including diagnosis, after first treatment, post-treatment, and relapse.[215] By studying samples at different points of tumor development, the researchers hope to identify the changes that drive tumor growth and resistance to treatment. The results of this project will help scientists and doctors gain a better understanding of NSCLC and potentially lead to the development of new treatments for the disease.[214] For lung cancer cases that develop resistance to epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors, new drugs are in development. EGFR inhibitors include afatinib and dacomitinib.[154] An alternative signaling pathway, c-Met, can be inhibited by tivantinib and onartuzumab. New ALK inhibitors include crizotinib and ceritinib.[216] If the MAPK/ERK pathway is involved, the BRAF kinase inhibitor dabrafenib and the MAPK/MEK inhibitor trametinib may be beneficial.[217] The PI3K pathway has been investigated as a target for lung cancer therapy. The most promising strategies for targeting this pathway seem to be selective inhibition of one or more members of the class I PI3Ks, and co-targeted inhibition of this pathway with others such as MEK.[218] Lung cancer stem cells are often resistant to conventional chemotherapy and radiotherapy. This may lead to relapse after treatment. New approaches target protein or glycoprotein markers that are specific to the stem cells. Such markers include CD133, CD90, ALDH1A1, CD44 and ABCG2. 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Seminars in Oncology. 41 (1): 126–32. doi:10.1053/j.seminoncol.2013.12.014. PMC 4732704. PMID 24565586. 212. ^ a b c d e Syn NL, Teng MW, Mok TS, Soo RA (December 2017). "De-novo and acquired resistance to immune checkpoint targeting". The Lancet. Oncology. 18 (12): e731–e741. doi:10.1016/s1470-2045(17)30607-1. PMID 29208439. 213. ^ a b Forde PM, Brahmer JR, Kelly RJ (May 2014). "New strategies in lung cancer: epigenetic therapy for non-small cell lung cancer". Clinical Cancer Research. 20 (9): 2244–8. doi:10.1158/1078-0432.ccr-13-2088. PMC 4325981. PMID 24644000. 214. ^ a b Jamal-Hanjani M, Hackshaw A, Ngai Y, Shaw J, Dive C, Quezada S, et al. (July 2014). "Tracking genomic cancer evolution for precision medicine: the lung TRACERx study". PLOS Biology. 12 (7): e1001906. doi:10.1371/journal.pbio.1001906. PMC 4086714. PMID 25003521. 215. ^ TRACERx project, Cancer Research UK science blog Archived 29 November 2014 at the Wayback Machine 216. ^ Spaans JN, Goss GD (August 2014). "Trials to Overcome Drug Resistance to EGFR and ALK Targeted Therapies - Past, Present, and Future". Frontiers in Oncology. 4 (233): 233. doi:10.3389/fonc.2014.00233. PMC 4145253. PMID 25221748. 217. ^ Weart TC, Miller KD, Simone CB (April 2018). "Spotlight on dabrafenib/trametinib in the treatment of non-small-cell lung cancer: place in therapy". Cancer Management and Research. 10: 647–652. doi:10.2147/CMAR.S142269. PMC 5892608. PMID 29662327. 218. ^ Heavey S, O'Byrne KJ, Gately K (April 2014). "Strategies for co-targeting the PI3K/AKT/mTOR pathway in NSCLC". Cancer Treatment Reviews. 40 (3): 445–56. doi:10.1016/j.ctrv.2013.08.006. PMID 24055012. 219. ^ Prabavathy D, Swarnalatha Y, Ramadoss N (March 2018). "Lung cancer stem cells-origin, characteristics and therapy". Stem Cell Investigation. 5 (6): 6. doi:10.21037/sci.2018.02.01. PMC 5897668. PMID 29682513. ## External links[edit] Wikimedia Commons has media related to Cancers of bronchus and lung. Wikiquote has quotations related to: Lung cancer * Lung cancer at Curlie Classification D * ICD-10: C33-C34 * ICD-9-CM: 162 * OMIM: 211980 * MeSH: D002283 * DiseasesDB: 7616 External resources * MedlinePlus: 007194 * eMedicine: med/1333 med/1336 emerg/335 radio/807 radio/405 radio/406 * Patient UK: Lung cancer * NCI: Lung cancer * 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 Authority control * GND: 4008343-3 * LCCN: sh85078900 * NDL: 00562782 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Lung cancer	c0153493	27,078	wikipedia	https://en.wikipedia.org/wiki/Lung_cancer	2021-01-18T18:57:34	{"umls": ["C0153493", "C0153492", "C0153491", "C0024624"], "icd-9": ["162162"], "icd-10": ["C3333.-C3434."], "wikidata": ["Q47912"]}
A number sign (#) is used with this entry because of evidence that autosomal recessive deafness-114 (DFNB114) is caused by homozygous mutation in the GRAP gene (604330) on chromosome 17p11. Description DFNB114 is characterized by congenital profound sensorineural hearing loss (Li et al., 2019). Clinical Features Li et al. (2019) studied 2 consanguineous families of Turkish origin in which a brother and sister in each family had nonsyndromic congenital profound sensorineural hearing loss. None of the affected individuals displayed nystagmus, experienced vertigo, or had problems with balance. Molecular Genetics In a cohort of 63 consanguineous multiplex families from Turkey and Iran with autosomal recessive nonsyndromic hearing loss, negative for mutation in known deafness genes, Li et al. (2019) performed exome and genome sequencing and identified 2 Turkish families in which 4 affected individuals were homozygous for a missense mutation in the GRAP gene (Q104L; 604330.0001). The mutation segregated with disease in both families and was not found in more than 500 in-house Turkish exomes. Analysis of flanking SNP markers indicated shared ancestry for the variant. INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Hearing loss, sensorineural, congenital (profound) MISCELLANEOUS \- Prelingual onset MOLECULAR BASIS \- Caused by mutation in the GRB2-related adapter protein gene (GRAP, 604330.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	DEAFNESS, AUTOSOMAL RECESSIVE 114	None	27,079	omim	https://www.omim.org/entry/618456	2019-09-22T15:41:51	{"omim": ["618456"]}
A number sign (#) is used with this entry because of evidence that premature ovarian failure-12 (POF12) is caused by homozygous mutation in the SYCE1 gene (611486) on chromosome 10q26. One such family has been reported. Homozygous mutation in SYCE1 has also been reported in spermatogenic failure (see SPGF15, 616950). For a general phenotypic description and discussion of genetic heterogeneity of premature ovarian failure, see POF1 (311360). Clinical Features De Vries et al. (2014) reported a consanguineous Arab family in which 2 sisters had primary amenorrhea. The first presented at 17 years of age with Tanner stage 5 breast development and pubic hair, but no onset of menses. She had elevated serum gonadotropins and low estradiol, and transabdominal ultrasound revealed a small prepubertal uterus and ovaries, with 2 small follicles on the left and 3 on the right. Hormone replacement therapy induced growth of the uterus to normal adult dimensions and regular menstruation. She married at age 21, and pregnancy was induced by intrauterine insemination; however, despite normal hormone and ultrasound findings in the first 4 weeks, the pregnancy ended in early fetal demise. Repeated cycles of assisted fertilization failed. On reevaluation of ovarian function 1 year later, antimullerian hormone level was very low and estradiol was undetectable. Her younger sister presented at age 16 for failure of breast development and primary amenorrhea, with Tanner stage 1 breasts and Tanner stage 4 pubic and axillary hair. She had elevated gonadotropins and low estradiol, and pelvic ultrasound revealed a small prepubertal uterus with very small ovaries in which no follicles were detected. A 33-year-old sister, who had been married for many years and was childless, appeared to be affected but declined to participate in the study. All 3 sisters exhibited macular dystrophy; however, the eye phenotype was also present in other family members with normal puberty and fertility, and appeared to represent a separate disease in the family. Molecular Genetics In 2 sisters from a consanguineous Arab family with primary ovarian failure, who were negative for FMR1 (309550) gene premutation and for adrenal antibodies, de Vries et al. (2014) performed homozygosity mapping followed by exome sequencing and identified homozygosity for a nonsense mutation in the SYCE1 gene (Q205X; 611486.0001). The mutation segregated with disease and was not found in 90 ethnically matched individuals or in 300 in-house control exomes. Analysis of the sisters' exome data did not reveal any disease-causing mutations in known POF-associated genes. De Vries et al. (2014) noted that although both sisters carried the same mutation, their clinical presentation varied between normal pubertal development with primary amenorrhea and failure to enter puberty at all; they stated that diverse expressivity of POF phenotypes had been observed both within and between families for most classes of mutations. INHERITANCE \- Autosomal recessive CHEST Breasts \- Absent thelarche (in some patients) GENITOURINARY Internal Genitalia (Female) \- Primary amenorrhea \- Small prepubertal uterus \- Small ovaries \- Few to no ovarian follicles ENDOCRINE FEATURES \- Primary amenorrhea \- Elevated serum FSH \- Elevated serum LH \- Low to undetectable serum estradiol MISCELLANEOUS \- Based on report of 2 sisters from a consanguineous Arab family (last curated May 2016) MOLECULAR BASIS \- Caused by mutation in the synaptonemal complex central element protein-1 gene (SYCE1, 611486.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	PREMATURE OVARIAN FAILURE 12	c4310782	27,080	omim	https://www.omim.org/entry/616947	2019-09-22T15:47:24	{"omim": ["616947"]}
Sudden temporary weakening of the heart muscle Takotsubo cardiomyopathy Other namesTransient apical ballooning syndrome,[1] apical ballooning cardiomyopathy,[2] stress-induced cardiomyopathy, broken-heart syndrome Schematic representation of takotsubo cardiomyopathy (A) compared to a normal heart (B) SpecialtyCardiology Takotsubo cardiomyopathy or Takotsubo syndrome (TTS), also known as stress cardiomyopathy, is a type of non-ischemic cardiomyopathy in which there is a sudden temporary weakening of the muscular portion of the heart.[3] It usually appears after a significant stressor, either physical or emotional; when caused by the latter, the condition is sometimes called broken heart syndrome.[4] Examples of physical stressors that can cause TTS are sepsis, shock, and pheochromocytoma, and emotional stressors include bereavement, divorce, or the loss of a job.[5] Reviews suggest that of patients diagnosed with the condition, about 70-80% recently experienced a major stressor including 41-50% with a physical stressor and 26-30% with an emotional stressor.[6][7] TTS can also appear in patients who have not experienced major stressors.[8][7] The pathophysiology is not well understood, but a sudden massive surge of catecholamines such as adrenaline and norepinephrine from extreme stress or a tumor secreting these chemicals is thought to play a central role.[9] Excess catecholamines, when released directly by nerves that stimulate cardiac muscle cells, have a toxic effect and can lead to decreased cardiac muscular function or "stunning".[10][11] Further, this adrenaline surge triggers the arteries to tighten, thereby raising blood pressure and placing more stress on the heart, and may lead to spasm of the coronary arteries that supply blood to the heart muscle.[9] This impairs the arteries from delivering adequate blood flow and oxygen to the heart muscle.[9] Together, these events can lead to congestive heart failure and decrease the heart's output of blood with each squeeze.[9] Takotsubo cardiomyopathy occurs worldwide.[10] The condition is thought to be responsible for 2% of all acute coronary syndrome cases presenting to hospitals.[10] Although TTS has generally been considered a self-limiting disease, spontaneously resolving over the course of days to weeks, contemporary observations show that the rates of cardiogenic shock and death in TTS are comparable to those of acute coronary syndrome (ACS) patients.[5] These cases of shock and death have been associated with the occurrence of TTS secondary to an enciting physical stressor such as hemorrhage, brain injury sepsis, pulmonary embolism or severe COPD.[10] It occurs more commonly in postmenopausal women.[10] The name "takotsubo" comes from the Japanese word takotsubo "octopus trap", because the left ventricle of the heart takes on a shape resembling an octopus trap when affected by this condition.[12] ## Contents * 1 Risk factors * 1.1 Stress trigger * 1.2 Gender * 1.3 Genetic risk factors * 1.4 Hormonal dysregulation * 2 Signs and symptoms * 3 Pathophysiology * 4 Diagnosis * 5 Treatment * 5.1 Heart failure * 5.2 Low blood pressure * 6 Prognosis * 7 Epidemiology * 8 History * 9 References * 10 External links ## Risk factors[edit] ### Stress trigger[edit] Although there have been documented cases of TTS without a triggering stressor, it is widely recognized that TTS is preceded by a stressful event.[11] Case series looking at large groups of patients report that some patients develop takotsubo cardiomyopathy after an emotional stress. Some patients have a preceding clinical stressor (such as a brain injury, asthma attack or exacerbation of a chronic illness) and research has indicated that this type of stress may even occur more often than emotionally stressful triggers.[8] Roughly one-third of patients have no preceding stressful event.[13] A 2009 large case series from Europe found that takotsubo cardiomyopathy was slightly more frequent during the winter season. This may be related to two possible/suspected pathophysiological causes: coronary spasms of microvessels, which are more prevalent in cold weather, and viral infections – such as Parvovirus B19 – which occur more frequently during the winter.[1] ### Gender[edit] Women, specifically postmenopausal women, are at greatest risk of developing TTS.[11] This has led some researchers to theorize about the possible protective effects of estrogen in preventing TTS.[14][5] ### Genetic risk factors[edit] It is currently being investigated if certain genetic traits associated with catecholamine receptors found on cardiac muscle cells play a role in the development of TTS.[14] There is limited evidence tying TTS directly to a specific genetic expression or mutation, however there is currently a widely held hypothesis supporting the idea of the interaction between environmental factors and the interplay of genetic predisposition leading to the susceptibility to microvascular alterations that contribute to the TTS disease process.[5] ### Hormonal dysregulation[edit] Certain endocrine diseases including pheochromocytoma and thyrotoxicosis have been identified as potential risk factors for TTS.[15][16] The relationship between thyroid function and stress cardiomyopathy is marked by a dual phenotype, where both impending primary hyperthyroidism and a high set point of thyroid homeostasis (encoding type 2 allostatic load) are common phenomena.[17] A multi-centre observation study found normal thyroid function to be the exception rather than the rule in TTS.[17] Especially hyperthyroidism is highly prevalent in takotsubo cardiomyopathy, and it seems to predict a poor prognosis in terms of complications and mortality.[18] ## Signs and symptoms[edit] The typical presentation of takotsubo cardiomyopathy is chest pain with or without shortness of breath and associated electrocardiogram (ECG) changes mimicking a myocardial infarction of the anterior wall. During the course of evaluation of the patient, a bulging out of the left ventricular apex with a hypercontractile base of the left ventricle is often noted. It is the hallmark bulging-out of the apex of the heart with preserved function of the base that earned the syndrome its name takotsubo "octopus trap", in Japan, where it was first described.[19] Stress is the main factor in takotsubo cardiomyopathy, with more than 85% of cases set in motion by either a physically or emotionally stressful event that prefaces the start of symptoms.[20] Examples of emotional stressors include grief from the death of a loved one, fear of public speaking, arguing with a spouse, relationship disagreements, betrayal, and financial problems.[20] Acute asthma, surgery, chemotherapy, and stroke are examples of physical stressors.[20] In a few cases, the stress may be a happy event, such as a wedding, winning a jackpot, a sporting triumph, or a birthday.[21][22] ## Pathophysiology[edit] The cause of takotsubo cardiomyopathy is not fully understood, but several mechanisms have been proposed.[23] It is well documented that elevated catecholamine levels have been implicated in the vast majority of TTS cases. Theories suggest a link between brain activation of stress-related biochemicals and the effects these chemicals have on areas of the heart. More specifically, adrenal stimulation by the sympathetic nervous system has been noted in cases ranging from physical events such as ischemic stroke, to emotional events such as depression or loss of a loved-one.[24] How these increased levels of catecholamines act in the body to produce the changes seen with TTS is not clearly understood.[5][10][11][14] Research supports the widely-held understanding that microvascular dysfunction and coronary vasospasm caused by a rapid influx of catecholamines to cardiac myocytes results in apical stunning and transient cardiomyopathy.[5][10][11] 1. Microvascular dysfunction/Transient vasospasm: Some of the original researchers of takotsubo suggested that multiple simultaneous spasms of coronary arteries could cause enough loss of blood flow to cause transient stunning of the myocardium.[25] Other researchers have shown that vasospasm is much less common than initially thought.[26][27][28] It has been noted that when there are vasospasms, even in multiple arteries, that they do not correlate with the areas of myocardium that are not contracting.[29] However, the idea of coronary artery vasospasm is still believed to contribute to the TTS disease process. The theory of vasospasm is not easily separated from that of microvascular dysfunction and in fact, microvascular dysfunction could explain vasospasticity.[11] Impaired microvascular function is seen in a vast majority, if not all, of patients with TTS and is currently one of the most supported theories.[5][14] Most of the dysfunction occurs as a result of abnormalities within the endothelial linings of blood vessels supplying the heart.[14] In TTS, these highly sensitive interior linings of the vessels have reduced functionality which create dysregulation of vascular tone and predispose the individual to vasoconstriction. When the increased vasoconstrictor effects of catecholamines are introduced, the result is acute cardiac ischemia.[5][11][14] 2. Catecholamine-induced myocyte injury: It has been suggested that the response to catecholamines (such as epinephrine and norepinephrine, released in response to stress) leads to heart muscle dysfunction that contributes to takotsubo cardiomyopathy.[11] The effects of this toxicity can be greater in those with a predisposition to anxiety or panic disorders.[10] Delivery of catecholamines (epinephrine, norepinephrine) via circulating blood and through direct delivery from cardiac nerves is increased by the stimulation of stress control centers of the brain.[10] During an emotionally or physically stressful event, brain centers initiate the sympathetic nervous pathways and increase myocardial activity. Excessive catecholamine stimulation has a toxic effect on cardiac muscle cells which creates necrosis of the contractile units of cells similarly seen during acute myocardial infarction.[5][11] The increased workload of cardiac muscle created by the stimulation of catecholamines, increases the need for more blood and oxygen to these muscles to sustain function. When these demands are unable to be met, the heart is starved of blood and oxygen and begins to die.[10] Included in the cytotoxic sequela of catecholamine toxicity is the molecular transformation of the cardiac myocyte to produce apical stunning. 3. Mid-ventricular obstruction, apical stunning: It has been suggested that a mid-ventricular wall thickening with outflow obstruction is important in the pathophysiology.[30] This stunning is largely seen as a protective effect produced by the flood of excess catecholamines into the cardiac muscle cell.[11] Overstimulation of catecholamine receptors create physiological changes in the receptor which has an inverse effect on cardiac cellular function. Termed 'cellular-trafficking', this property of the cardiac muscle cell is actually a molecular transformation of the cell to produce a down-regulation of catecolaminergic sensitivity.[10] This means that in the presence of excess epinephrine, a normal cardiac contraction is inhibited in an effort to reduce energy demands, prevent hyperactivity and spare the integrity of the cell.[10][11] Further bolstering this idea is the concentration of these kinds of receptors in the heart. Higher concentrations of the receptor effected to produce cardiac stunning are found closer to the apex of the ventricle. This is what creates the classic ballooning effect of the ventricle.[10][11] It is likely that there are multiple factors at play that could include some amount of vasospasm and failure of the microvasculature. These factors can overlap and create the complex sequela leading to ischemia and left ventricle contraction abnormality.[11] For instance, estrogen, which confers protection to women by improving blood flow to heart muscle, is one biochemical pathway implicated in the TTS disease process. Once this protective mechanism is reduced through the decreased production of estrogen after menopause, there is thought to be an increase in endothelial dysfunction predisposing an individual to vasoconstriction and cardiac ischemia.[10] An inciting stressful event elicits the release of catecholamines into the blood stream to create increased heart muscle activity and metabolism. This leads to further cardiac microvascular endothelial dysfunction through oxidative stress, alteration of ion-mediated channels, and electrolyte disturbances which ultimately alter myocardial cell membrane permeability and dysfunction.[5][11] Coupled with direct heart muscle toxicity, this crescendo of factors are implicated in the ballooning and heart failure characteristically seen in TTS.[5][10][11][14] A 2019 case involved a 60-year-old woman presenting with Takotsubo cardiomyopathy due to over-consumption of wasabi, mistaking it for avocado.[31] ## Diagnosis[edit] Several well regarded institutions of medical research have produced clinical criteria useful in diagnosing TTS. One of the first sets of guidelines was initially published in 2004 and again in 2008 by the Mayo Clinic. Other research institutions proposing diagnostic criteria include the Japanese Takotsubo Cardiomyopathy Study Group, Gothenburg University, Johns Hopkins University, the Takotsubo Italian Network and the Heart Failure Associates TTS Taskforce of the European Society of Cardiology.[32] All of the research institutions agree on at least two main criteria needed to accurately diagnose TTS: 1) transient left ventricular wall motion abnormality and 2) the absence of a condition obviously explaining this wall motion abnormality (coronary artery lesion, hypoperfusion, myocarditis, toxicity, etc.). Other commonly acknowledged criteria necessary for diagnosis include characteristic EKG changes and mild to modest elevation in cardiac troponin.[32] Transient apical ballooning syndrome or takotsubo cardiomyopathy is found in 1.7–2.2% of patients presenting with acute coronary syndrome.[1] While the original case studies reported on individuals in Japan, takotsubo cardiomyopathy has been noted more recently in the United States and Western Europe. It is likely that the syndrome previously went undiagnosed before it was described in detail in the Japanese literature. Evaluation of individuals with takotsubo cardiomyopathy typically includes a coronary angiogram to rule out occlusion of the left anterior descending artery, which will not reveal any significant blockages that would cause the left ventricular dysfunction. Provided that the individual survives their initial presentation, the left ventricular function improves within two months. The diagnosis of takotsubo cardiomyopathy may be difficult upon presentation. The ECG findings often are confused with those found during an acute anterior wall myocardial infarction.[33][34] It classically mimics ST-segment elevation myocardial infarction, and is characterised by acute onset of transient ventricular apical wall motion abnormalities (ballooning) accompanied by chest pain, shortness of breath, ST-segment elevation, T-wave inversion or QT-interval prolongation on ECG. Cardiac enzymes are usually negative and are moderate at worst, and cardiac catheterization usually shows absence of significant coronary artery disease.[1] The diagnosis is made by the pathognomonic wall motion abnormalities, in which the base of the left ventricle is contracting normally or is hyperkinetic while the remainder of the left ventricle is akinetic or dyskinetic. This is accompanied by the lack of significant coronary artery disease that would explain the wall motion abnormalities. Although apical ballooning has been described classically as the angiographic manifestation of takotsubo, it has been shown that left ventricular dysfunction in this syndrome includes not only the classic apical ballooning, but also different angiographic morphologies such as mid-ventricular ballooning and, rarely, local ballooning of other segments.[1][35][36][37][38] The ballooning patterns were classified by Shimizu et al. as takotsubo type for apical akinesia and basal hyperkinesia, reverse takotsubo for basal akinesia and apical hyperkinesia, mid-ventricular type for mid-ventricular ballooning accompanied by basal and apical hyperkinesia, and localised type for any other segmental left ventricular ballooning with clinical characteristics of takotsubo-like left ventricular dysfunction.[36] In short, the main criteria for the diagnosis of takotsubo cardiomyopathy are: the patient must have experienced a stressor before the symptoms began to arise; the patient's ECG reading must show abnormalities from a normal heart; the patient must not show signs of coronary blockage or other common causes of heart troubles; the levels of cardiac enzymes in the heart must be elevated or irregular; and the patient must recover complete contraction and be functioning normally in a short amount of time.[39] * Left ventriculography during systole showing apical ballooning akinesis with basal hyperkinesis in a characteristic takotsubo ventricle * Left ventriculogram during systole displaying the characteristic apical ballooning with apical motionlessness in a patient with takotsubo cardiomyopathy * (A) Echocardiogram showing dilatation of the left ventricle in the acute phase (B) Resolution of left ventricular function on repeat echocardiogram six days later * ECG showing sinus tachycardia and non-specific ST and T wave changes from a person with confirmed takotsubo cardiomyopathy * Play media Echocardiogram showing the effects of the disease[40] ## Treatment[edit] The treatment of takotsubo cardiomyopathy is generally supportive in nature, for it is considered a transient disorder.[41] Treatment is dependent on whether patients experience heart failure or acute hypotension and shock. In many individuals, left ventricular function normalizes within two months.[42][43] Aspirin and other heart drugs also appear to help in the treatment of this disease, even in extreme cases.[44][45] After the patient has been diagnosed, and myocardial infarction (heart attack) ruled out, the aspirin regimen may be discontinued, and treatment becomes that of supporting the patient.[46] There is currently no internationally agreed protocol for treatment of this condition. While medical treatments are important to address the acute symptoms of takotsubo cardiomyopathy, further treatment includes lifestyle changes.[47] It is important that the individual stay physically healthy while learning and maintaining methods to manage stress, and to cope with future difficult situations. Although the symptoms of takotsubo cardiomyopathy usually go away on their own and the condition completely resolves itself within a few weeks, some serious short and long-term complications can happen that must be treated.[48] These most commonly include congestive heart failure and very low blood pressure, and less commonly include blood clotting in the apex of the left ventricle, irregular heart beat, and tearing of the heart wall.[48] ### Heart failure[edit] For patients in acute heart failure, ACE inhibitors, angiotensin receptor blockers, and beta blockers, are considered mainstays of heart failure treatment. But use of beta blockers specifically for takotsubo cardiomyopathy is controversial, because they may confer no benefit.[41] ### Low blood pressure[edit] For people with cardiogenic shock, medical treatment is based on whether a left ventricular outflow tract (LVOT) obstruction is present.[49] Therefore, early echocardiography is necessary to determine proper management. For those with obstructed LVOTs inotropic agents should not be used, but instead should be managed like patients with hypertrophic cardiomyopathy, (e.g. phenylephrine and fluid resuscitation).[41] For cases in which the LVOT is not obstructed, inotropic therapy (e.g. dobutamine and dopamine) may be used, but with the consideration that takotsubo is caused by excess catecholamines.[49] Furthermore, mechanical support with an intra-aortic balloon pump (IABP) is well-established as supportive treatment.[49][50] ## Prognosis[edit] Despite the grave initial presentation in some of the patients, most of the patients survive the initial acute event, with a very low rate of in-hospital mortality or complications. Once a patient has recovered from the acute stage of the syndrome, they can expect a favorable outcome and the long-term prognosis is excellent for most.[1][19][35] Even when ventricular systolic function is heavily compromised at presentation, it typically improves within the first few days and normalises within the first few months.[1][26][27][28] Although infrequent, recurrence of the syndrome has been reported and seems to be associated with the nature of the trigger.[1][13] Stress cardiomyopathy is now a well-recognized cause of acute congestive heart failure, lethal abnormal heart rhythms, and rupture of the heart wall.[12] ## Epidemiology[edit] Takotsubo cardiomyopathy is rare, affecting between 1.2% and 2.2% of people in Japan and 2% to 3% in Western countries who suffer a myocardial infarction. It also affects far more women than men with 90% of cases being women, most postmenopausal. Scientists believe one reason is that estrogen causes the release of catecholamine and glucocorticoid in response to mental stress. It is not likely for the same recovered patient to experience the syndrome twice, although it has happened in rare cases.[51] The average ages at onset are between 58 and 75 years. Less than 3% of cases occurred in patients under age 50.[52] ## History[edit] The Japanese octopus traps after which this disease is named[12] Rees, et al. wrote in 1967 that the death of a close relative increases the risk of dying within one year by a factor of seven.[53] Engel wrote about sudden and rapid death during psychological stress in 1971 and itemized 8 causation categories: [1] on the impact of the collapse or death of a close person; [2] during acute grief; [3] on threat of loss of a close person; [4] during mourning or on an anniversary; [5] on loss of status or self-esteem; [6] personal danger or threat of injury; [7] after the danger is over; [8] reunion, triumph, or happy ending. He proposed these events provoke neurovegetative responses, involving both the flight-fight and conservation-withdrawal systems, conducive to lethal cardiac events, particularly in individuals with preexisting cardiovascular disease.[54] Although the first scientific description of takotsubo cardiomyopathy was not until the 1990s, Cebelin and Hirsch wrote about human stress cardiomyopathy in 1980. The two looked at homicidal assaults that had happened in Cuyahoga County, Ohio, the past 30 years, specifically those with autopsies who had no internal injury, but had died of physical assault. They found that 11 of 15 had myofibrillar degeneration similar to animal stress studies. In the end, they concluded their data supported "the theory of catecholamine mediation of these myocardial changes in man and of the lethal potential of stress through its effect on the heart".[55] The first studied case of takotsubo cardiomyopathy was in Japan in 1991 by Sato et al. More cases of the syndrome appeared in Japan within the next decade, although western medicine had still not acknowledged it. The syndrome finally occurred in 1997 when Pavin, et al., wrote about two cases of "reversible LV dysfunction precipitated by acute emotional stress." The western world had not heard of such a thing at the time, as it was incredibly rare and often misdiagnosed. The Japanese at last reported about the syndrome to the west in 2001 under the name "transient LV apical ballooning" though at this point the west had already heard of numerous cases. The syndrome reached international audiences through the media in 2005 when the New England Journal of Medicine wrote about the syndrome.[56] ## References[edit] 1. ^ a b c d e f g h Eshtehardi P, Koestner SC, Adorjan P, Windecker S, Meier B, Hess OM, Wahl A, Cook S (July 2009). "Transient apical ballooning syndrome—clinical characteristics, ballooning pattern, and long-term follow-up in a Swiss population". Int. J. 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Treasure Island (FL): StatPearls Publishing. PMID 28613549.[1] 46. ^ Derrick, Dawn (2009). "The "Broken Heart Syndrome": Understanding Takotsubo Cardiomyopathy". Critical Care Nurse. 29 (1): 49–57. doi:10.4037/ccn2009451. PMID 19182280. 47. ^ "Broken Heart Syndrome – National Heart, Lung, and Blood Institute". www.nhlbi.nih.gov. Retrieved 2 January 2018. 48. ^ a b Kurisu, S; Kihara, Y (2014). "Clinical management of takotsubo cardiomyopathy". Circulation Journal. 78 (7): 1559–66. doi:10.1253/circj.cj-14-0382. PMID 24964980. 49. ^ a b c "Management and prognosis of stress (takotsubo) cardiomyopathy". www.uptodate.com. Retrieved 21 October 2017. 50. ^ Akashi, Yoshihiro J.; Goldstein, David S.; Barbaro, Giuseppe; Ueyama, Takashi (16 December 2008). "Takotsubo Cardiomyopathy: A New Form of Acute, Reversible Heart Failure". Circulation. 118 (25): 2754–2762. doi:10.1161/CIRCULATIONAHA.108.767012. ISSN 0009-7322. PMC 4893309. PMID 19106400. 51. ^ Schneider B.; Athanasiadis A.; Sechtem U. (2013). "Gender-Related differences in Takotsubo Cardiomyopathy". Heart Failure Clinics. 9 (2): 137–146. doi:10.1016/j.hfc.2012.12.005. PMID 23562114. 52. ^ Prasad A, Lerman A, Rihal CS (March 2008). "Apical ballooning syndrome (Tako-Tsubo or stress cardiomyopathy): A mimic of acute myocardial infarction". American Heart Journal. 155 (3): 408–17. doi:10.1016/j.ahj.2007.11.008. PMID 18294473. 53. ^ Rees WD, Lutkins SG (1967). "Mortality of Bereavement". British Medical Journal. 4 (5570): 13–16. doi:10.1136/bmj.4.5570.13. PMC 1748842. PMID 6047819. 54. ^ Engel, George L. (1971). "Sudden and Rapid Death During Psychological Stress: Folklore or Folk Wisdom?". Annals of Internal Medicine. 74 (5): 771–83. doi:10.7326/0003-4819-74-5-771. PMID 5559442. 55. ^ Cebelin, Hirsch (1980). "Human stress cardiomyopathy. Myocardial lesions in victims of homicidal assaults without internal injuries". Human Pathology. 11 (2): 123–32. doi:10.1016/s0046-8177(80)80129-8. PMID 7399504. 56. ^ Wittstein I (2007). "The broken heart syndrome". Cleveland Clinic Journal of Medicine. 74 (1): S17–S22. doi:10.3949/ccjm.74.Suppl_1.S17. PMID 17455537. ## External links[edit] * Krishnan, Lakshmi; Marchalik, Daniel (8 September 2018). "Understanding Heartbreak: From Takotsubo to Wuthering Heights". The Lancet. 392 (10150): 812. doi:10.1016/S0140-6736(18)32061-0. S2CID 54271789. Retrieved 25 September 2019. * Wagner, Judith N. (Fall 2014). "Death by voodoo: truth or tale?". Hektoen International Journal. 6 (4). ISSN 2155-3017. * Takotsubo Network \- website for professionals and people who have experienced Takotsubo Classification D * ICD-10: I42.8 * ICD-9-CM: 429.83 * MeSH: D054549 * DiseasesDB: 33976 External resources * eMedicine: article/1513631 * v * t * e Cardiovascular disease (heart) Ischaemic Coronary disease * Coronary artery disease (CAD) * Coronary artery aneurysm * Spontaneous coronary artery dissection (SCAD) * Coronary thrombosis * Coronary vasospasm * Myocardial bridge Active ischemia * Angina pectoris * Prinzmetal's angina * Stable angina * Acute coronary syndrome * Myocardial infarction * Unstable angina Sequelae * hours * Hibernating myocardium * Myocardial stunning * days * Myocardial rupture * weeks * Aneurysm of heart / Ventricular aneurysm * Dressler syndrome Layers Pericardium * Pericarditis * Acute * Chronic / Constrictive * Pericardial effusion * Cardiac tamponade * Hemopericardium Myocardium * Myocarditis * Chagas disease * Cardiomyopathy * Dilated * Alcoholic * Hypertrophic * Tachycardia-induced * Restrictive * Loeffler endocarditis * Cardiac amyloidosis * Endocardial fibroelastosis * Arrhythmogenic right ventricular dysplasia Endocardium / valves Endocarditis * infective endocarditis * Subacute bacterial endocarditis * non-infective endocarditis * Libman–Sacks endocarditis * Nonbacterial thrombotic endocarditis Valves * mitral * regurgitation * prolapse * stenosis * aortic * stenosis * insufficiency * tricuspid * stenosis * insufficiency * pulmonary * stenosis * insufficiency Conduction / arrhythmia Bradycardia * Sinus bradycardia * Sick sinus syndrome * Heart block: Sinoatrial * AV * 1° * 2° * 3° * Intraventricular * Bundle branch block * Right * Left * Left anterior fascicle * Left posterior fascicle * Bifascicular * Trifascicular * Adams–Stokes syndrome Tachycardia (paroxysmal and sinus) Supraventricular * Atrial * Multifocal * Junctional * AV nodal reentrant * Junctional ectopic Ventricular * Accelerated idioventricular rhythm * Catecholaminergic polymorphic * Torsades de pointes Premature contraction * Atrial * Junctional * Ventricular Pre-excitation syndrome * Lown–Ganong–Levine * Wolff–Parkinson–White Flutter / fibrillation * Atrial flutter * Ventricular flutter * Atrial fibrillation * Familial * Ventricular fibrillation Pacemaker * Ectopic pacemaker / Ectopic beat * Multifocal atrial tachycardia * Pacemaker syndrome * Parasystole * Wandering atrial pacemaker Long QT syndrome * Andersen–Tawil * Jervell and Lange-Nielsen * Romano–Ward Cardiac arrest * Sudden cardiac death * Asystole * Pulseless electrical activity * Sinoatrial arrest Other / ungrouped * hexaxial reference system * Right axis deviation * Left axis deviation * QT * Short QT syndrome * T * T wave alternans * ST * Osborn wave * ST elevation * ST depression * Strain pattern Cardiomegaly * Ventricular hypertrophy * Left * Right / Cor pulmonale * Atrial enlargement * Left * Right * Athletic heart syndrome Other * Cardiac fibrosis * Heart failure * Diastolic heart failure * Cardiac asthma * Rheumatic fever [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Takotsubo cardiomyopathy	c1739395	27,081	wikipedia	https://en.wikipedia.org/wiki/Takotsubo_cardiomyopathy	2021-01-18T19:05:57	{"gard": ["9400"], "mesh": ["D054549"], "umls": ["C1739395", "C1168291"], "icd-9": ["429.83"], "orphanet": ["66529"], "wikidata": ["Q595907"]}
A number sign (#) is used with this entry because of evidence that infantile-onset multisystem autoimmune disease-2 (ADMIO2) is caused by compound heterozygous mutation in the ZAP70 gene (176947) on chromosome 2q12. One such family has been reported. For a discussion of genetic heterogeneity of ADMIO, see ADMIO1 (615952). Clinical Features Chan et al. (2016) reported a brother and sister, born of unrelated Caucasian parents, with onset of a systemic autoimmune disorder in the first months of life. The boy developed nephrotic syndrome at age 9 months, and renal biopsy showed mild IgG deposition with widespread foot process effacement consistent with minimal change disease. By age 20 months, he developed blistering skin disease, and biopsy showed bullous pemphigoid, with subepidermal clefting, infiltration with eosinophils and neutrophils, and IgG deposition at the basement membrane and intercellularly. He developed bleeding due to F8 (300841) autoantibodies at age 2 and inflammatory colitis at age 3. His autoimmune disease became refractory to high-dose steroids and multiple immunosuppressive regimens. His sister developed bullous pemphigoid at 1 month of age, followed by inflammatory colitis, proteinuria in the absence of nephrotic syndrome, and autoimmune hypothyroidism. Neither child had recurrent infections. Immunologic workup showed mild T and B cell lymphopenia and reduced numbers of CD8+ T cells. Both patients also had a decreased T-cell proliferative responses. Both patients underwent hematopoietic stem cell transplant, resulting in complete resolution of the disorder. Inheritance The transmission pattern of ADMIO2 in the family reported by Chan et al. (2016) was consistent with autosomal recessive inheritance. Molecular Genetics In 2 sibs with ADMIO2, Chan et al. (2016) identified compound heterozygous missense mutations in the ZAP70 gene (R192W, 176947.0006 and R360P, 176947.0007). The mutations were found by whole-exome sequencing and segregated with the disorder in the family. Studies of transfected cell lines and cells from the carrier parents showed that the R192W was a hypomorphic allele with reduced binding to phosphorylated T cell receptor (TCR) zeta-chain (CD247; 186780), whereas R360P was weakly hyperactive compared to wildtype, most likely due to disruption of the autoinhibitory mechanism. The combination of hypomorphic and activating mutations suggested a novel disease mechanism, resulting in a theretofore undescribed human ZAP70-associated autoimmune disease. INHERITANCE \- Autosomal recessive ABDOMEN Gastrointestinal \- Inflammatory colitis GENITOURINARY Kidneys \- Nephrotic syndrome (1 patient) \- IgG deposition (1 patient) \- Effacement of podocytes (1 patient) \- Minimal change disease (1 patient) \- Proteinuria SKIN, NAILS, & HAIR Skin \- Blistering skin disease \- Bullous pemphigoid ENDOCRINE FEATURES \- Autoimmune hypothyroidism (1 patient) HEMATOLOGY \- Autoantibodies to factor VIII (1 boy) IMMUNOLOGY \- Autoimmune disorder \- Autoantibody production \- Decreased numbers of CD8+ T cells \- Diminished proliferative response of T cells MISCELLANEOUS \- Onset in infancy \- A brother and sister from 1 family have been reported (last curated June 2016) \- Both patients had resolution of symptoms after hematopoietic stem cell transplantation MOLECULAR BASIS \- Caused by mutation in the zeta-chain-associated protein kinase gene (ZAP70, 176947.0006 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	AUTOIMMUNE DISEASE, MULTISYSTEM, INFANTILE-ONSET, 2	c4310768	27,082	omim	https://www.omim.org/entry/617006	2019-09-22T15:47:46	{"omim": ["617006"]}
Levodopa-induced dyskinesia SpecialtyNeurology Levodopa-induced dyskinesia (LID) is a form of dyskinesia associated with levodopa (l-DOPA), used to treat Parkinson's disease. It often involves hyperkinetic movements, including chorea, dystonia, and athetosis.[1] In the context of Parkinson's disease (PD), dyskinesia is often the result of long-term dopamine therapy. These motor fluctuations occur in up to 80% of PD patients after 5–10 years of l-DOPA treatment,[2] with the percentage of affected patients increasing over time.[3] Based on the relationship with levodopa dosing, dyskinesia most commonly occurs at the time of peak l-DOPA plasma concentrations and is thus referred to as peak-dose dyskinesia (PDD). As patients advance, they may present with symptoms of diphasic dyskinesia (DD), which occurs when the drug concentration rises or falls. If dyskinesia becomes too severe or impairs the patient's quality of life, a reduction in l-Dopa might be necessary, however this may be accompanied by a worsening of motor performance. Therefore, once established, LID is difficult to treat.[4] Amongst pharmacological treatments, N-methyl-D-aspartate (NMDA) antagonist, (a glutamate receptor), amantadine, has been proven to be clinically effective in a small number of placebo controlled randomized controlled trials, while many others have only shown promise in animal models.[5][6] Attempts to moderate dyskinesia by the use of other treatments such as bromocriptine (Parlodel), a dopamine agonist, appears to be ineffective.[7] In order to avoid dyskinesia, patients with the young-onset form of the disease or young-onset Parkinson's disease (YOPD) are often hesitant to commence l-DOPA therapy until absolutely necessary for fear of suffering severe dyskinesia later on. Alternatives include the use of DA agonists (i.e. ropinirole or pramipexole) in lieu of early l-DOPA treatment which delays the use of l-DOPA. Additionally, a review [8] shows that highly soluble l-DOPA prodrugs may be effective in avoiding the in vivo blood concentration swings that potentially lead to motor fluctuations and dyskinesia. ## Contents * 1 Mechanism * 2 Treatment * 3 References * 4 External links ## Mechanism[edit] Levodopa-induced dyskinesia has long been thought to arise through pathological alterations in pre-synaptic and post-synaptic signal transduction in the nigrostriatal pathway (dorsal striatum).[9] It is thought that the stage of illness, dosage of l-DOPA, frequency of l-DOPA treatment and the youth of the patient at the onset of symptoms; contributes to the severity of the involuntary movements associated with LID.[4] In experiments employing real-time electrophysiological recordings in awake and active animals, LIDs have been shown to be strongly associated with cortical gamma-oscillations with accompanying Δc-fos overexpression, proposedly due to a dysregulation of dopamine signaling in the cortico-basal ganglia circuitry. This was concluded partially from reduced tyrosine hydroxylase (TH) staining in the cortex - and the fact that a dopamine receptor 1 antagonist, delivered exclusively to the cortex, relieved the dyskinesia at its peak-time.[10] ΔFosB overexpression in the dorsal striatum (nigrostriatal dopamine pathway) via viral vectors generates levodopa-induced dyskinesia in animal models of Parkinson's disease.[11][12] Dorsal striatal ΔFosB is overexpressed in rodents and primates with dyskinesias;[12] moreover, postmortem studies of individuals with Parkinson's disease that were treated with levodopa have also observed similar dorsal striatal ΔFosB overexpression.[12] ## Treatment[edit] Levetiracetam, an antiepileptic drug which has been demonstrated to reduce the severity of levodopa-induced dyskinesias, has been shown to dose-dependently decrease the induction of dorsal striatal ΔFosB expression in rats when co-administered with levodopa. Although the signal transduction mechanism involved in this effect is unknown.[12] Nicotine (administered by dermal adhesive patches) has also been shown to improve Levodopa-induced dyskinesia and other PD symptoms.[13][14] Patients with prominent dyskinesia resulting from high doses of antiparkinsonian medications may benefit from deep brain stimulation (DBS), which may benefit the patient in two ways: 1) DBS theoretically allows a reduction in l-DOPA dosage of 50–60% (tackling the underlying cause); 2) DBS treatment itself (in the subthalamic nucleus or globus pallidus) has been shown to reduce dyskinesia.[15] Mavoglurant is also currently studied by Novartis for the treatment of this disease. On August 24, 2017 the FDA approved a drug to treat levodopa-induced dyskinesia for Parkinson's patients. The drug, Gocovri, is amantadine manufactured by Adamas Pharmaceuticals. It is the first FDA approved treatment for this condition.[16] ## References[edit] 1. ^ Gerlach, Manfred; Peter Riederer; Dieter Scheller (December 2011). "Mechanisms underlying and medical management of L-Dope-associated motor complications". Journal of Neural Transmission. 118 (12): 1659–1660. doi:10.1007/s00702-011-0728-0. PMID 22075781. 2. ^ Ahlskog JE, Muenter MD (2001). "Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature". Mov Disord. 16 (3): 448–458. doi:10.1002/mds.1090. 3. ^ Obeso JA; et al. (2000). "The evolution and origin of motor complications in Parkinson's disease". Neurology. 55 (S4): S13–S20. PMID 11147505. 4. ^ a b Thanvi, Bhomraj; Nelson Lo; Tom Robinson (2007). "Levodopa-induced dyskinesia in Parkinson's disease: clinical features, pathogenesis, prevention and treatment". Postgraduate Medical Journal. 83 (980): 384–388. doi:10.1136/pgmj.2006.054759. PMC 2600052. PMID 17551069. 5. ^ Rascol, Olivier; Goetz C.; Koller W.; Poewe W.; Sampaio C. (May 2002). "Treatment interventions for Parkinson's disease: an evidence based assessment". The Lancet. 359 (9317): 1589–1598. doi:10.1016/S0140-6736(02)08520-3. PMID 12047983. 6. ^ Wolf, Elisabeth; Seppi,K.; Katzenschlager, R.; Hochschorner, G.; Ransmayr, G.; Schwinenschuh, P.; Ott, E.; Kloiber, I.; Haubenberger, D.; Auff, E.; Poewe, W. (2010). "Long-term antidyskinetic efficacy of amantadine in Parkinson's Disease". Movement Disorders. 25 (10): 1357–1363. doi:10.1002/mds.23034. PMID 20198649. 7. ^ van Hilten J; Ramaker C; Stowe R; Nj Ives (2007). "Bromocriptine/levodopa combined versus levodopa alone for early Parkinson's disease". Cochrane Database Syst Rev. 4 (4): CD003634. doi:10.1002/14651858.cd003634.pub2. PMID 17943795. 8. ^ Stocchi F, Marconi S (2010). "Factors associated with motor fluctuations and dyskinesia in Parkinson Disease: potential role of a new melevodopa plus carbidopa formulation (Sirio)". Clin Neuropharmacol. 33 (4): 198–203. doi:10.1097/WNF.0b013e3181de8924. PMID 20414107. 9. ^ Cenci MA (2014). "Presynaptic Mechanisms of l-DOPA-Induced Dyskinesia: The Findings, the Debate, and the Therapeutic Implications". Front Neurol. 5: 242. doi:10.3389/fneur.2014.00242. PMC 4266027. PMID 25566170. "The dopamine (DA) precursor l-DOPA has been the most effective treatment for Parkinson's disease (PD) for over 40 years. The response to this treatment changes with disease progression, and most patients develop dyskinesias (abnormal involuntary movements) and motor fluctuations within a few years of l-DOPA therapy. There is wide consensus that these motor complications depend on both pre- and post-synaptic disturbances of nigrostriatal DA transmission." 10. ^ Halje, P; Tamtè, M; Richter, U; Mohammed, M; Cenci, MA; Petersson, P (21 November 2012). "Levodopa-induced dyskinesia is strongly associated with resonant cortical oscillations" (PDF). The Journal of Neuroscience. 32 (47): 16541–51. doi:10.1523/jneurosci.3047-12.2012. PMC 6621755. PMID 23175810. 11. ^ Cao X, Yasuda T, Uthayathas S, Watts RL, Mouradian MM, Mochizuki H, Papa SM (May 2010). "Striatal overexpression of DeltaFosB reproduces chronic levodopa-induced involuntary movements". J. Neurosci. 30 (21): 7335–7343. doi:10.1523/JNEUROSCI.0252-10.2010. PMC 2888489. PMID 20505100. 12. ^ a b c d Du H, Nie S, Chen G, Ma K, Xu Y, Zhang Z, Papa SM, Cao X (2015). "Levetiracetam Ameliorates L-DOPA-Induced Dyskinesia in Hemiparkinsonian Rats Inducing Critical Molecular Changes in the Striatum". Parkinson's Disease. 2015: 1–9. doi:10.1155/2015/253878. PMC 4322303. PMID 25692070. "Furthermore, the transgenic overexpression of ΔFosB reproduces AIMs in hemiparkinsonian rats without chronic exposure to L-DOPA [13]. ... FosB/ΔFosB immunoreactive neurons increased in the dorsolateral part of the striatum on the lesion side with the used antibody that recognizes all members of the FosB family. All doses of levetiracetam decreased the number of FosB/ΔFosB positive cells (from 88.7 ± 1.7/section in the control group to 65.7 ± 0.87, 42.3 ± 1.88, and 25.7 ± 1.2/section in the 15, 30, and 60 mg groups, resp.; Figure 2). These results indicate dose-dependent effects of levetiracetam on FosB/ΔFosB expression. ... In addition, transcription factors expressed with chronic events such as ΔFosB (a truncated splice variant of FosB) are overexpressed in the striatum of rodents and primates with dyskinesias [9, 10]. ... Furthermore, ΔFosB overexpression has been observed in postmortem striatal studies of Parkinsonian patients chronically treated with l-DOPA [26]. ... Of note, the most prominent effect of levetiracetam was the reduction of ΔFosB expression, which cannot be explained by any of its known actions on vesicular protein or ion channels. Therefore, the exact mechanism(s) underlying the antiepileptic effects of levetiracetam remains uncertain." 13. ^ Decamp E, Schneider JS (2009). "Interaction between nicotinic and dopaminergic therapies on cognition in a chronic Parkinson model". Brain Res. 1262: 109–14. doi:10.1016/j.brainres.2009.01.028. PMC 2706019. PMID 19368843. 14. ^ Louis Elan D.; Benito-León Julián; Bermejo-Pareja Félix (2008). "Population-Based Prospective Study of Cigarette Smoking and Risk of Incident Essential Tremor". Neurology. 70 (19): 1682–1687. doi:10.1212/01.wnl.0000311271.42596.32. PMC 2683619. PMID 18458228. 15. ^ Toda Hiroki; Hamani Clement; Lozano Andres (2004). "Deep Brain Stimulation in the Treatment of Dyskinesia and Dystonia". Neurosurg Focus. 17 (1): 9–13. doi:10.3171/foc.2004.17.1.2. 16. ^ "Gocovri (Amantadine)". Parkinson's News Today. Retrieved 4 February 2019. ## External links[edit] Classification D [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Levodopa-induced dyskinesia	None	27,083	wikipedia	https://en.wikipedia.org/wiki/Levodopa-induced_dyskinesia	2021-01-18T18:29:37	{"wikidata": ["Q6535765"]}
Porphyria cutanea tarda Other namesPCT Blister on the hand of a person with porphyria cutanea tarda SpecialtyEndocrinology Porphyria cutanea tarda is the most common subtype of porphyria.[1] The disease is named because it is a porphyria that often presents with skin manifestations later in life. The disorder results from low levels of the enzyme responsible for the fifth step in heme production. Heme is a vital molecule for all of the body's organs. It is a component of hemoglobin, the molecule that carries oxygen in the blood. Hepatoerythropoietic porphyria has been described as a homozygous form of porphyria cutanea tarda,[2] although it can also be caused if two different mutations occur at the same locus. ## Contents * 1 Signs and symptoms * 1.1 Vitamin, mineral, and enzyme deficiencies * 2 Genetics * 2.1 Other * 2.2 Exacerbating factors * 3 Pathogenesis * 4 Diagnosis * 4.1 Classification * 5 Treatment * 6 Epidemiology * 7 Society and culture * 8 References * 9 External links ## Signs and symptoms[edit] Porphyria cutanea tarda (commonly referred to as PCT) is recognized as the most prevalent subtype of porphyritic diseases.[3] The disease is characterized by onycholysis and blistering of the skin in areas that receive higher levels of exposure to sunlight. The primary cause of this disorder is a deficiency of uroporphyrinogen decarboxylase (UROD), a cytosolic enzyme that is a step in the enzymatic pathway that leads to the synthesis of heme. While a deficiency in this enzyme is the direct cause leading to this disorder, there are a number of both genetic and environmental risk factors that are associated with PCT.[4] Typically, patients who are ultimately diagnosed with PCT first seek treatment following the development of photosensitivities in the form of blisters and erosions on commonly exposed areas of the skin. This is usually observed in the face, hands, forearms, and lower legs. It heals slowly and with scarring. Though blisters are the most common skin manifestations of PCT, other skin manifestations like hyperpigmentation (as if they are getting a tan) and hypertrichosis (mainly on top of the cheeks) also occur. PCT is a chronic condition, with external symptoms often subsiding and recurring as a result of a number of factors. In addition to the symptomatic manifestation of the disease in the skin, chronic liver problems are extremely common in patients with the sporadic form of PCT. These include hepatic fibrosis (scarring of the liver), cirrhosis, and inflammation. However, liver problems are less common in patients with the inherited form of the disease.[5] Additionally, patients will often void a wine-red color urine with an increased concentration of uroporphyrin I due to their enzymatic deficiency.[6] ### Vitamin, mineral, and enzyme deficiencies[edit] Certain vitamin and minerals deficiencies are commonly found in people with porphyria cutanea tarda. The most frequently cited deficiencies are those of beta-Carotene,[7] retinol,[8] vitamin A[9] and vitamin C. Beta-Carotene is required to synthesize vitamin A and vitamin A is needed to synthesize retinol. A lack of retinol-binding protein is due to a lack of retinol which is required to trigger its production.[9] The damaging effects of porphyrins interacting with iron, absorbing photons to then emit reactive oxygen species is the mechanism of action that results in the itchy, painful blisters that are common with PCT.[7] The reactive oxygen species that are formed interact with and exhaust the antioxidants in the skin, primarily those of beta-carotene, vitamin E, and vitamin C. Supplementation of these three vitamins has been shown to decrease these oxidative effects and potentially diminish the severity of blister formation.[10] No single vitamin of these three will inhibit the damaging effects of oxidized porphyrins, specifically uroporphyrins and coproporphyrins, but all three working together synergistically are capable of neutralizing their damaging effects. ## Genetics[edit] The reaction catalyzed by UroD 20% of cases of porphyria cutanea tarda are inherited in an autosomal dominant pattern. Inherited mutations in the UROD gene cause about 20% of cases (the other 80% of cases do not have mutations in UROD, and are classified as sporadic). UROD makes an enzyme called uroporphyrinogen III decarboxylase, which is critical to the chemical process that leads to heme production. The activity of this enzyme is usually reduced by 50% in all tissues in people with the inherited form of the condition. Nongenetic factors such as alcohol abuse, excess iron, and others listed above can increase the demand for heme and the enzymes required to make heme. The combination of this increased demand and reduced activity of uroporphyrinogen decarboxylase disrupts heme production and allows byproducts of the process to accumulate in the body, triggering the signs and symptoms of porphyria cutanea tarda. The HFE gene makes a protein that helps cells regulate the absorption of iron from the digestive tract and into the cells of the body. Certain mutations in the HFE gene cause hemochromatosis (an iron overload disorder). People who have these mutations are also at an increased risk of developing porphyria cutanea tarda. In the 20% of cases where porphyria cutanea tarda is inherited, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene is sufficient to decrease enzyme activity and cause the signs and symptoms of the disorder. ### Other[edit] While inherited deficiencies in uroporphyrinogen decarboxylase often lead to the development of PCT, there are a number of risk factors that can both cause and exacerbate the symptoms of this disease. One of the most common risk factors observed is infection with the Hepatitis C virus.[11] One review of a collection of PCT studies noted Hepatitis C infection in 50% of documented cases of PCT. Additional risk factors include alcohol abuse, excess iron (from iron supplements as well as cooking on cast iron skillets), and exposure to chlorinated cyclic hydrocarbons and Agent Orange. It can be a paraneoplastic phenomenon.[12] ### Exacerbating factors[edit] * Alcohol[13] * Estrogen * Iron[14] * Hepatitis C virus[15] ## Pathogenesis[edit] Porphyria cutanea tarda is primarily caused by uroporphyrinogen decarboxylase deficiency (UROD). Uroporphyrinogen decarboxylase occurs in nature as a homodimer of two subunits. It participates in the fifth step in heme synthesis pathway, and is active in the cytosol. This enzymatic conversion results in coproporphyrinogen III as the primary product. This is accomplished by the clockwise removal of the four carboxyl groups present in the cyclic uroporphyrinogen III molecule. Therefore, a deficiency in this enzyme causes the aforementioned buildup of uroporphyrinogen and hepta-carboxylic porphyrinogen, and to a lesser extent hexa-carboxylic porphyrinogen, and penta-carboxylic porphyrinogen in the urine, which can be helpful in the diagnosis of this disorder.[16][17] The dermatological symptoms of PCT that include blistering and lesions on sun-exposed areas of the skin are caused by a buildup of porphyrin compounds (specifically uroporphyrinogen) close to the surface of the skin that have been oxidized by free radicals or sunlight.[18] The oxidized porphyrins initiate degranulation of dermal mast cells,[19] which release proteases that catabolize the surrounding proteins.[20] This begins a cell-mediated positive feedback loop which matches the description of a type 4 delayed hypersensitivity reaction.[citation needed] The resulting blisters, therefore, do not appear immediately but begin to show up 2–3 days after sun exposure. Due to the highly conjugated structure of porphyrins involving alternating single and double carbon bonds, these compounds exhibit a deep purple color, resulting in the discoloration observed in the skin. Excess alcohol intake decreases hepcidin production which leads to increased iron absorption from the gut and an increase in oxidative stress. This oxidative stress then leads to inhibition of uroporphyrinogen decarboxylase, creating an excess of uroporphyrinogen III which is oxidized from the relatively harmless porphyrinogens into their oxidized porphyrins form.[21] Concentrated instances of oxidative stress (alcohol, physical trauma, psychological stress, etc.) cause the liver to hemorrhage these porphyrins into the blood stream where they are then susceptible to oxidation. The strong association of PCT with Hepatitis C infection is not entirely understood. Studies have suggested that the cytopathic effect of the virus on hepatocytes can lead to the release of free iron. This iron can disrupt the activity of cytochrome p450, releasing activated oxygen species. These can oxidize the UROD substrate uroporphyrinogen, which can result in the inhibition of UROD and lead to deficient activity of this key enzyme. Excess alcohol abuse is frequently associated with both inducing PCT[22] and aggravating a preexisting diagnosis of the disorder. It is thought to do so by causing oxidative damage to liver cells, resulting in oxidized species of uroporphyrinogen that inhibit the activity of hepatic UROD. It is also felt to increase the uptake of iron in liver cells, leading to further oxidation of uroporphyrinogen by the release of activated oxygen species. Additionally, exposure to chlorinated cyclic hydrocarbons can lead to a deficiency in the activity of uroporphyrinogen decarboxylase, causing the buildup of excess uroporphyrinogen. Additionally, alcohol has been shown to increase the activity of the delta-aminolevulinic acid synthetase (ALA synthetase), the rate-limiting enzymatic step in heme synthesis in the mitochondria, in rats.[23] Therefore, alcohol consumption may increase the production of uroporphyrinogen, exacerbating symptoms in individuals with porphyria cutanea tarda.[citation needed] ## Diagnosis[edit] While the most common symptom of PCT is the appearance of skin lesions and blistering, their appearance does not single-handedly lead to a conclusive diagnosis. Laboratory testing will commonly reveal high levels of uroporphyrinogen in the urine, clinically referred to as uroporphyrinogenuria. Additionally, testing for common risk factors such as Hepatitis C and hemochromatosis is strongly suggested, as their high prevalence in patients with PCT may require additional treatment. If clinical appearance of PCT is present, but laboratories are negative, one needs to seriously consider the diagnosis of pseudoporphyria. ### Classification[edit] Some sources divide PCT into two types: sporadic and familial.[2] Other sources include a third type,[24] but this is less common. Type OMIM Description Type I ("sporadic") 176090 Type I porphyria cutanea tarda, the sporadic form, is indicated by UROD deficiency that is observed only in hepatic cells and nowhere else in the body. Genetically, these individuals will not exhibit deficiency in the UROD gene, although other genetic factors such as HFE deficiency (resulting in hemochromatosis and the buildup of iron in the liver) are thought to play a key role. Typically in these individuals, a variety of risk factors such as alcohol abuse and Hepatitis C infection conspire to result in the clinical manifestation of PCT. Type II ("familial") 176100 Patients exhibiting Type II PCT have a specific deficiency in the UROD gene, passed down in an autosomal dominant pattern. Those possessing this deficiency are heterozygous for the UROD gene. They do not show a complete lack of functional uroporphyrinogen decarboxylase, only a deficient form of the enzyme that is marked by reduced conversion of uroporphyrinogen to coproporphyrinogen. Therefore, the expression of uroporphyrinogen decarboxylase will be reduced throughout the body of these individuals, while it is isolated to the liver in Type I patients. While this genetic deficiency is the main distinction between Type I and Type II PCT, the risk factors mentioned before are often seen in patients presenting with Type II PCT. In fact, many people who possess the deficient UROD gene often go their entire lives without having a clinical manifestation of PCT symptoms. Type III \- The least common is Type III, which is no different from Type I insofar as the patients possess normal UROD genes. Despite this, Type III PCT is observed in more than one family member, indicating a genetic component unrelated to the expression of uroporphyrinogen decarboxylase. One study used 74% as the cutoff for UROD activity, with those patients under that number being classified as type II, and those above classified as type III if there was a family history, and type I if there was not.[25] Genetic variants associated with hemochromatosis have been observed in PCT patients,[13] which may help explain inherited PCT not associated with UROD. ## Treatment[edit] Since PCT is a chronic condition, a comprehensive management of the disease is the most effective means of treatment. Primarily, it is key that patients diagnosed with PCT avoid alcohol consumption, iron supplements, excess exposure to sunlight (especially in the summer), as well as estrogen and chlorinated cyclic hydrocarbons, all of which can potentially exacerbate the disorder. Additionally, the management of excess iron (due to the commonality of hemochromatosis in PCT patients) can be achieved through phlebotomy, whereby blood is systematically drained from the patient. A borderline iron deficiency has been found to have a protective effect by limiting heme synthesis. In the absence of iron, which is to be incorporated in the porphyrin formed in the last step of the synthesis, the mRNA of erythroid 5-aminolevulinate synthase (ALAS-2) is blocked by attachment of an iron-responsive element (IRE) binding cytosolic protein, and transcription of this key enzyme is inhibited.[26] Low doses of antimalarials can be used.[27] Orally ingested chloroquine is completely absorbed in the gut and is preferentially concentrated in the liver, spleen, and kidneys.[28] They work by removing excess porphyrins from the liver via increasing the excretion rate by forming a coordination complex with the iron center of the porphyrin as well as an intramolecular hydrogen bond between a propionate side chain of the porphyrin and the protonated quinuclidine nitrogen atom of either alkaloid.[29] Due to the presence of the chlorine atom, the entire complex is more water-soluble allowing the kidneys to preferentially remove it from the blood stream and expel it through urination.[28][30][31] Chloroquine treatment can induce porphyria attacks within the first couple of months of treatment due to the mass mobilization of porphyrins from the liver into the blood stream.[28] Complete remission can be seen within 6–12 months as each dose of antimalarial can only remove a finite amount of porphyrins and there are generally decades of accumulation to be cleared. Originally, higher doses were used to treat the condition but are no longer recommended because of liver toxicity.[32][33] Finally, due to the strong association between PCT and Hepatitis C, the treatment of Hepatitis C (if present) is vital to the effective treatment of PCT. Chloroquine, hydroxychloroquine, and venesection are typically employed in the management strategy.[34] ## Epidemiology[edit] Porphyria cutanea tarda has a prevalence estimated at approximately 1 in 10,000.[35] An estimated 80% of porphyria cutanea tarda cases are sporadic. The exact frequency is not clear because many people with the condition never experience symptoms and those that do are often misdiagnosed with anything ranging from idiopathic photodermatitis and seasonal allergies to hives. ## Society and culture[edit] Porphyria cutanea tarda is implicated in the origin of vampire myths. This is because people with the disease tend to avoid the sun due to photosensitivity and may develop disfigurement that eats away their noses, eyelids, lips, and gums giving their teeth a fang-like appearance. It has also been suggested they may have developed a craving for healthy blood to replace their own in a self medicated treatment in prior centuries. Some Folklore scholars claim that this is a mistake, first suggested in the 1990s,[citation needed] as vampires of myth did not have photosensitivity, nor were they described as looking like the modern incarnation of vampires. They were described as unintelligent roaming beings who fed on their victims to the point that they became reddened and heavily bloated, fattened on blood. Fangs were very rarely mentioned. Photosensitivity was not added to the vampire mythology until the 1922 film Nosferatu. Count Dracula, of Bram Stroker's novel, himself could walk about freely in daylight unharmed but not as powerful in the book. Porphyria Cutanea Tarda is the name of a song by the rock band AFI on their fourth album Black Sails in the Sunset, released on May 18, 1999. Porphyria cutanea tarda is the disease that both Dabney Pratt and Brother Rush suffer from in Virginia Hamilton's children's novel Sweet Whispers, Brother Rush. ## References[edit] 1. ^ Phillips, J. D.; Bergonia, H. A.; Reilly, C. A.; Franklin, M. R.; Kushner, J. P. (2007). "A porphomethene inhibitor of uroporphyrinogen decarboxylase causes porphyria cutanea tarda". Proceedings of the National Academy of Sciences. 104 (12): 5079–84. Bibcode:2007PNAS..104.5079P. doi:10.1073/pnas.0700547104. JSTOR 25427147. PMC 1820519. PMID 17360334. 2. ^ a b "porphyria cutanea tarda" at Dorland's Medical Dictionary 3. ^ Danton, Malcolm; Lim, Chang Kee (2007). "Porphomethene inhibitor of uroporphyrinogen decarboxylase: Analysis by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry". Biomedical Chromatography. 21 (7): 661–3. doi:10.1002/bmc.860. PMID 17516469. 4. ^ Kushner, J P; Barbuto, A J; Lee, G R (1976). "An inherited enzymatic defect in porphyria cutanea tarda: Decreased uroporphyrinogen decarboxylase activity". Journal of Clinical Investigation. 58 (5): 1089–97. doi:10.1172/JCI108560. PMC 333275. PMID 993332. 5. ^ Di Padova, C.; Marchesi, L.; Cainelli, T.; Gori, G.; Podenzani, S.A.; Rovagnati, P.; Rizzardini, M.; Cantoni, L. (1983). "Effects of Phlebotomy on Urinary Porphyrin Pattern and Liver Histology in Patients with Porphyria Cutanea Tarda". The American Journal of the Medical Sciences. 285 (1): 2–12. doi:10.1097/00000441-198301000-00001. PMID 6824014. 6. ^ Goljan, E. F. (2011). Pathology (3rd ed., rev. reprint.). Philadelphia, PA: Mosby/Elsevier.[page needed] 7. ^ a b Rocchi, E.; Stella, A. M.; Cassanelli, M.; Borghi, A.; Nardella, N.; Seium, Y.; Casalgrandi, G. (1 July 1995). "Liposoluble vitamins and naturally occurring carotenoids in porphyria cutanea tarda". European Journal of Clinical Investigation. 25 (7): 510–514. doi:10.1111/j.1365-2362.1995.tb01737.x. PMID 7556369. 8. ^ Rocchi, E.; Casalgrandi, G.; Masini, A.; Giovannini, F.; Ceccarelli, D.; Ferrali, M.; Marchini, S.; Ventura, E. (1 December 1999). "Circulating pro- and antioxidant factors in iron and porphyrin metabolism disorders". Italian Journal of Gastroenterology and Hepatology. 31 (9): 861–867. PMID 10669994. 9. ^ a b Benoldi, D.; Manfredi, G.; Pezzarossa, E.; Allegra, F. (1 December 1981). "Retinol binding protein in normal human skin and in cutaneous disorders". The British Journal of Dermatology. 105 (6): 659–665. doi:10.1111/j.1365-2133.1981.tb00976.x. PMID 7032574. 10. ^ Böhm, F.; Edge, R.; Foley, S.; Lange, L.; Truscott, T. G. (31 December 2001). "Antioxidant inhibition of porphyrin-induced cellular phototoxicity". Journal of Photochemistry and Photobiology. B, Biology. 65 (2–3): 177–183. doi:10.1016/s1011-1344(01)00259-7. PMID 11809377. 11. ^ Azim, James; McCurdy, H; Moseley, R. H. (2008). "Porphyria cutanea tarda as a complication of therapy for chronic hepatitis C". World Journal of Gastroenterology. 14 (38): 5913–5. doi:10.3748/wjg.14.5913. PMC 2751904. PMID 18855993. 12. ^ Sökmen, M; Demirsoy, H; Ersoy, O; Gökdemir, G; Akbayir, N; Karaca, C; Ozdil, K; Kesici, B; Calişkan, C; Yilmaz, B (2007). "Paraneoplastic porphyria cutanea tarda associated with cholangiocarcinoma: Case report". The Turkish Journal of Gastroenterology. 18 (3): 200–5. PMID 17891697. 13. ^ a b Frank, J; Poblete-Gutiérrez, P; Weiskirchen, R; Gressner, O; Merk, H. F.; Lammert, F (2006). "Hemochromatosis gene sequence deviations in German patients with porphyria cutanea tarda" (PDF). Physiological Research. 55 Suppl 2: S75–83. PMID 17298224. 14. ^ Sampietro, M; Fiorelli, G; Fargion, S (1999). "Iron overload in porphyria cutanea tarda". Haematologica. 84 (3): 248–53. PMID 10189391. 15. ^ "Porphyria Cutanea Tarda (PCT)". 2020-01-12. 16. ^ https://labtestsonline.org/understanding/analytes/porphyrins/tab/test/[full citation needed] 17. ^ Jackson, A. H.; Ferramola, A. M.; Sancovich, H. A.; Evans, N; Matlin, S. A.; Ryder, D. J.; Smith, S. G. (1976). "Hepta- and hexa-carboxylic porphyrinogen intermediates in haem biosynthesis". Annals of Clinical Research. 8 Suppl 17: 64–9. PMID 1008499. 18. ^ Miller, Dennis M.; Woods, James S. (1993). "Urinary porphyrins as biological indicators of oxidative stress in the kidney". Biochemical Pharmacology. 46 (12): 2235–41. doi:10.1016/0006-2952(93)90614-3. PMID 8274157. 19. ^ Brun, Atle; Sandberg, Sverre (1991). "Mechanisms of photosensitivity in porphyric patients with special emphasis on erythropoietic protoporphyria". Journal of Photochemistry and Photobiology B: Biology. 10 (4): 285–302. doi:10.1016/1011-1344(91)80015-A. PMID 1791486. 20. ^ Lim, H. W. (1989). "Mechanisms of phototoxicity in porphyria cutanea tarda and erythropoietic protoporphyria". Immunology Series. 46: 671–85. PMID 2488874. 21. ^ Ryan Caballes, F.; Sendi, Hossein; Bonkovsky, Herbert L. (2012). "Hepatitis C, porphyria cutanea tarda and liver iron: An update". Liver International. 32 (6): 880–93. doi:10.1111/j.1478-3231.2012.02794.x. PMC 3418709. PMID 22510500. 22. ^ Porphyria Cutanea Tarda at eMedicine 23. ^ Held, H. (2009). "Effect of Alcohol on the Heme and Porphyrin Synthesis Interaction with Phenobarbital and Pyrazole". Digestion. 15 (2): 136–46. doi:10.1159/000197995. PMID 838185. 24. ^ Méndez, M.; Poblete-Gutiérrez, P.; García-Bravo, M.; Wiederholt, T.; Morán-Jiménez, M.J.; Merk, H.F.; Garrido-Astray, M.C.; Frank, J.; Fontanellas, A.; Enríquez De Salamanca, R. (2007). "Molecular heterogeneity of familial porphyria cutanea tarda in Spain: Characterization of 10 novel mutations in the UROD gene". British Journal of Dermatology. 157 (3): 501–7. doi:10.1111/j.1365-2133.2007.08064.x. hdl:11268/5436. PMID 17627795. 25. ^ Cruz-Rojo, J; Fontanellas, A; Morán-Jiménez, M. J.; Navarro-Ordóñez, S; García-Bravo, M; Méndez, M; Muñoz-Rivero, M. C.; De Salamanca, R. E. (2002). "Precipitating/aggravating factors of porphyria cutanea tarda in Spanish patients". Cellular and Molecular Biology (Noisy-le-Grand, France). 48 (8): 845–52. PMID 12699242. 26. ^ Thunell, S (2000). "Porphyrins, porphyrin metabolism and porphyrias. I. Update". Scandinavian Journal of Clinical and Laboratory Investigation. 60 (7): 509–40. doi:10.1080/003655100448310. PMID 11202048. 27. ^ Singal, Ashwani K.; Kormos–Hallberg, Csilla; Lee, Chul; Sadagoparamanujam, Vaithamanithi M.; Grady, James J.; Freeman, Daniel H.; Anderson, Karl E. (2012). "Low-Dose Hydroxychloroquine is as Effective as Phlebotomy in Treatment of Patients with Porphyria Cutanea Tarda". Clinical Gastroenterology and Hepatology. 10 (12): 1402–9. doi:10.1016/j.cgh.2012.08.038. PMC 3501544. PMID 22985607. 28. ^ a b c http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/006002s043lbl.pdf[full citation needed] 29. ^ De Villiers, Katherine A.; Gildenhuys, Johandie; Le Roex, Tanya (2012). "Iron(III) Protoporphyrin IX Complexes of the Antimalarial Cinchona Alkaloids Quinine and Quinidine". ACS Chemical Biology. 7 (4): 666–71. doi:10.1021/cb200528z. PMID 22276975. 30. ^ Asghari-Khiavi, Mehdi; Vongsvivut, Jitraporn; Perepichka, Inna; Mechler, Adam; Wood, Bayden R.; McNaughton, Don; Bohle, D. Scott (2011). "Interaction of quinoline antimalarial drugs with ferriprotoporphyrin IX, a solid state spectroscopy study". Journal of Inorganic Biochemistry. 105 (12): 1662–9. doi:10.1016/j.jinorgbio.2011.08.005. PMID 22079977. 31. ^ Alumasa, John N.; Gorka, Alexander P.; Casabianca, Leah B.; Comstock, Erica; De Dios, Angel C.; Roepe, Paul D. (2011). "The hydroxyl functionality and a rigid proximal N are required for forming a novel non-covalent quinine-heme complex". Journal of Inorganic Biochemistry. 105 (3): 467–75. doi:10.1016/j.jinorgbio.2010.08.011. PMC 3010338. PMID 20864177. 32. ^ Sweeney, G. D.; Saunders, S. J.; Dowdle, E. B.; Eales, L (1965). "Effects of Chloroquine on Patients with Cutaneous Porphyria of the "symptomatic" Type". British Medical Journal. 1 (5445): 1281–5. doi:10.1136/bmj.1.5445.1281. PMC 2166040. PMID 14278818. 33. ^ Scholnick, Perry L.; Epstein, John; Marver, Harvey S. (1973). "The Molecular Basis of the Action of Chloroquine in Porphyria Cutanea Tarda". Journal of Investigative Dermatology. 61 (4): 226–32. doi:10.1111/1523-1747.ep12676478. PMID 4744026. 34. ^ Sarkany, R. P. E. (2001). "The management of porphyria cutanea tarda". Clinical and Experimental Dermatology. 26 (3): 225–32. doi:10.1046/j.1365-2230.2001.00825.x. PMID 11422163. 35. ^ Arceci, Robert.; Hann, Ian M.; Smith, Owen P. (2006). Pediatric hematolog. Malden MA: Blackwell. ISBN 978-1-4051-3400-2.[page needed] ## External links[edit] * Porphyria cutanea tarda at NIH's Office of Rare Diseases Classification D * ICD-10: E80.1 * ICD-9-CM: 277.1 * OMIM: 176100 * MeSH: D017119 * DiseasesDB: 10376 External resources * eMedicine: derm/344 * Orphanet: 101330 * 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 Vesiculobullous disease Acantholysis (epidermis) Pemphigus * Pemphigus vulgaris: Pemphigus vegetans * of Hallopeau * of Neumann * Pemphigus foliaceus: Pemphigus erythematosus * Endemic pemphigus * Paraneoplastic pemphigus * IgA pemphigus * Subcorneal pustular * Intraepidermal neutrophilic Other * Transient acantholytic dermatosis Pemphigoid (dermis) IgG: * Bullous pemphigoid * Cicatricial pemphigoid * Localised * Gestational pemphigoid * Pemphigoid nodularis * Epidermolysis bullosa acquisita IgA: * Linear IgA bullous dermatosis * Childhood * Adult Other bullous * Dermatitis herpetiformis In diseases classified elsewhere * Porphyria cutanea tarda * Bullous lupus erythematosus * PUVA-induced acrobullous dermatosis * v * t * e Heme metabolism disorders Porphyria, hepatic and erythropoietic (porphyrin) early mitochondrial: * ALAD porphyria * Acute intermittent porphyria cytoplasmic: * Gunther disease/congenital erythropoietic porphyria * Porphyria cutanea tarda/Hepatoerythropoietic porphyria late mitochondrial: * Hereditary coproporphyria * Harderoporphyria * Variegate porphyria * Erythropoietic protoporphyria Hereditary hyperbilirubinemia (bilirubin) unconjugated: * Gilbert's syndrome * Crigler–Najjar syndrome * Lucey–Driscoll syndrome conjugated: * Dubin–Johnson syndrome nd sheet * Rotor 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-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Porphyria cutanea tarda	c0162566	27,084	wikipedia	https://en.wikipedia.org/wiki/Porphyria_cutanea_tarda	2021-01-18T18:32:43	{"gard": ["7433"], "mesh": ["D017119"], "umls": ["C0162566"], "orphanet": ["101330"], "wikidata": ["Q1479497"]}
Periostitis SpecialtyRheumatology Periostitis, also known as periostalgia, is a medical condition caused by inflammation of the periosteum, a layer of connective tissue that surrounds bone.[1] The condition is generally chronic, and is marked by tenderness and swelling of the bone and pain. ## Causes[edit] Acute periostitis is due to infection, is characterized by diffuse formation of pus, severe pain, constitutional symptoms, and usually results in necrosis. It can be caused by excessive physical activity as well, as in the case of medial tibial stress syndrome (also referred to as tibial periostalgia, soleus periostalgia, or shin splints). Congenital infection with syphilis can also cause periostitis in newborn infants. ## History[edit] Evidence for periostitis found in the fossil record is studied by paleopathologists, specialists in ancient disease and injury. Periostitis has been seen in the late Cretaceous-Eocene crocodile Borealosuchus formidabilis, once known as Leidyosuchus. In one study, periostitis was the most common pathology in this species, with 134 instances of the condition out of 7,154 bones the scientists examined showing evidence for the condition. Periostitis has also been documented in dinosaurs, including a forelimb referred to the long-necked Camarasaurus grandis, as well as the shoulder blade of a horned dinosaur.[2] ## See also[edit] * Periosteal reaction ## References[edit] 1. ^ Aufderheide, Arthur C.; Rodriguez-Martin, Conrado; Langsjoen, Odin M. (1998), The Cambridge Encyclopedia of Human Paleopathology, Cambridge University Press, pp. 179–181, ISBN 0521552036. 2. ^ McWhinney, L.; Carpenter, K.; Rothschild, B. (2001), Tanke, D. H.; Carpenter, K. (eds.), "Dinosaurian humeral periostitis: a case of a juxtacortical lesion in the fossil record", Mesozoic Vertebrate Life, Indiana University Press, pp. 364–377, ISBN 0253339073. ## External links[edit] Classification D * ICD-10: M90.1 * ICD-9-CM: 730 * MeSH: D010522 * DiseasesDB: 29059 * v * t * e Bone and joint disease Bone Inflammation endocrine: * Osteitis fibrosa cystica * Brown tumor infection: * Osteomyelitis * Sequestrum * Involucrum * Sesamoiditis * Brodie abscess * Periostitis * Vertebral osteomyelitis Metabolic * Bone density * Osteoporosis * Juvenile * Osteopenia * Osteomalacia * Paget's disease of bone * Hypophosphatasia Bone resorption * Osteolysis * Hajdu–Cheney syndrome * Ainhum * Gorham's disease Other * Ischaemia * Avascular necrosis * Osteonecrosis of the jaw * Complex regional pain syndrome * Hypertrophic pulmonary osteoarthropathy * Nonossifying fibroma * Pseudarthrosis * Stress fracture * Fibrous dysplasia * Monostotic * Polyostotic * Skeletal fluorosis * bone cyst * Aneurysmal bone cyst * Hyperostosis * Infantile cortical hyperostosis * Osteosclerosis * Melorheostosis * Pycnodysostosis Joint Chondritis * Relapsing polychondritis Other * Tietze's syndrome Combined Osteochondritis * Osteochondritis dissecans Child leg: * hip * Legg–Calvé–Perthes syndrome * tibia * Osgood–Schlatter disease * Blount's disease * foot * Köhler disease * Sever's disease spine * * Scheuermann's_disease arm: * wrist * Kienböck's disease * elbow * Panner disease [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Periostitis	c0031111	27,085	wikipedia	https://en.wikipedia.org/wiki/Periostitis	2021-01-18T19:10:20	{"mesh": ["D010522"], "umls": ["C0031111"], "icd-9": ["730"], "icd-10": ["M90.1"], "wikidata": ["Q1480377"]}
A rare, genetic, ectodermal dysplasia syndrome characterized by the association of hypohidrotic ectodermal dysplasia (manifesting with the triad of hypohidrosis, anodontia/hypodontia and hypotrichosis) with primary hypothyroidism and respiratory tract ciliary dyskinesia. Patients frequently present urticaria pigmentosa-like skin pigmentation, increased mast cells and melanin depositions in the dermis and severe, recurrent chest infections. There have been no further descriptions in the literature since 1986. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Hypohidrotic ectodermal dysplasia-hypothyroidism-ciliary dyskinesia syndrome	c1857052	27,086	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1882	2021-01-23T18:19:13	{"gard": ["2049"], "mesh": ["C565604"], "omim": ["225050"], "umls": ["C1857052"], "icd-10": ["Q82.4"], "synonyms": ["ANOTHER syndrome", "HEDH syndrome"]}
Inflammatory aortic aneurysm CT reconstruction image of an abdominal aortic aneurysm SpecialtyVascular surgery Inflammatory aortic aneurysm (IAA), also known as Inflammatory abdominal aortic aneurysm (IAAA), is a type of abdominal aortic aneurysm (AAA) where the walls of the aneurysm become thick and inflamed. Similar to AAA, IAA occurs in the abdominal region.[1] IAA is closely associated and believed to be a response to and extensive peri-aneurysmal fibrosis,[2] which is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process IAA accounts for 5-10% of aortic aneurysms. IAA occurs mainly in a population that is on average younger by 10 years than most AAA patients. Some common symptoms of IAA may include back pain, abdominal tenderness, fevers, weight loss or elevated Erythrocyte sedimentation rate (ESR) levels. Corticosteroids and other immunosuppressive drugs have been found to decrease symptoms and the degree of peri-aortic inflammation and fibrosis [3] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Mechanism * 4 Diagnosis * 5 Treatment * 6 Research * 7 References ## Signs and symptoms[edit] Inflammatory Aortic Aneurysms occur typically in a younger population compared to the typical Abdominal Aortic Aneurysm group. Risk of rupture for the IAA group, due to thinning of aneurysm walls, are also rare due to inflammation and fibrosis [4] Unruptured inflammatory AAAs are usually symptomatic: * abdominal or back pain (70 to 80%) * abdominal tenderness * fever * weight loss * elevated erythrocyte sedimentation rate (90%) ## Causes[edit] Although the exact cause is unknown, some risk factors associated with individuals with IAA are: Tobacco Use: Cigarette smoking and other forms of tobacco use appear to increase the risk of aortic aneurysms. In addition to the damaging effects that smoking causes directly to the arteries, smoking contributes to the buildup of fatty plaques in the arteries (atherosclerosis) and high blood pressure. Smoking may also cause an aneurysm to grow faster by further damaging the aorta. Hardening of the arteries (atherosclerosis). Atherosclerosis occurs when fat and other substances build up on the lining of a blood vessel, increasing the risk of an aneurysm. Infection in the aorta (vasculitis). In rare cases, abdominal aortic aneurysm may be caused by an infection or inflammation that weakens a section of the aortic wall.[3] ## Mechanism[edit] In general, an aneurysm is bulge that can occur in blood vessels or sometimes in the heart itself. In the case of IAA, this type of aneurysm is localized in the aortic artery, which is the artery that carries oxygenated blood from the heart to the rest of the body. This location is ideal for aneurysms to develop based upon the high stress and pressure from blood circulation. Fibrosis, a stiffening of the muscle, may occur due to the exposure to stress and blood pressure. In the development of the fibrosis an autoimmune response may occur which in the area causing the "inflammation." This inflammation is what gives IAA the characteristic thickened walls of the aneurysm. All types of abdominal aortic aneurysms occur in the part of the aorta that passes through the middle to low abdomen. Thoracic aortic aneurysms occur on the aorta as it passes through the chest cavity. These are less common than abdominal aneurysms. Small aneurysms generally pose no threat. However, aneurysms increase the risk for: * Atherosclerotic plaques to form at the site of the aneurysm, which causes further weakening of the artery wall. * blood clots may form at the site and dislodge, increasing the chance of stroke * Increase in the size of the aneurysm, causing it to press on other organs, which may cause pain. * Aneurysm may also rupture. It is fragile and may burst under stress. The rupture of an aortic aneurysm is a catastrophic, life-threatening event. ## Diagnosis[edit] Aortic aneurysms are often encountered during an X-ray, ultrasound, or echocardiogram done for other reasons.[3] IAA may also be found during a routine physical exam by feeling for bulges in the abdominal area. If an aortic aneurysm is suspected, medical history will be considered along with a physical examination. Further tests to locate the aneurysm may be required. When an aneurysm is suspected or diagnosed, it is important to:[4] * Pinpoint the location of the aneurysm. * Estimate its size. * Find out how fast it is growing. * Find out whether other blood vessels are involved. * See if there are blood clots or inflammation. Tests to help find out the location, size, and rate of growth of an aneurysm include: * Abdominal ultrasound \- This imaging allows the doctor to observe growth of the aneurysm. If the aneurysm is large, a monitoring ultrasound may need to occur every 6 to 12 months. If the aneurysm is small, monitoring may occur every 2 to 3 years. * Computed tomography (CT) and magnetic resonance angiogram (MRA) - These imaging techniques give a more detailed view of the aneurysm. These techniques may be used to gather information about aneurysm's relation to the blood vessels of the kidney or other organs. This information may be useful before surgery. CT is used to watch the growth of a thoracic aortic aneurysm. * Echocardiogram \- This ultrasound exam is used to study the heart. A transthoracic echocardiogram (TTE) or a transesophageal echocardiogram (TEE) may also be done to further diagnose thoracic aortic aneurysm. * Angiogram \- An angiogram can help identify the size of the aneurysm and reveal if there are any aortic dissections, blood clots, or other blood vessel involvement.[3] ## Treatment[edit] Corticosteroids and other immunosuppressive drugs have been found to decrease symptoms and the degree of peri-aortic inflammation and fibrosis.[3] ## Research[edit] 2002 the CT scan was assessed for it reliability for imaging inflammatory aortic aneurysms and to quantitatively evaluate its features. The finding were that CT scan was a reliable means to diagnose IAA.[5] 2008 a study was done to test the effectiveness of MRI and FDG-PET tests to detect, diagnose, and measure inflammatory aortic arch syndrome. The results from the study were that MRI and FDG-PET were unreliable techniques due to giant-cell arteritis.[6] 2015 following endovascular repair of an aortic aneurysm the type of the endograft’s material used for repair seems to play a role in the inflammatory response associated with IAA.[7] ## References[edit] 1. ^ Hellmann DB, Grand DJ, Freischlag JA (January 2007). "Inflammatory abdominal aortic aneurysm". JAMA. 297 (4): 395–400. doi:10.1001/jama.297.4.395. PMID 17244836. 2. ^ Ishizaka N, Sohmiya K, Miyamura M, Umeda T, Tsuji M, Katsumata T, Miyata T (2012). "Infected aortic aneurysm and inflammatory aortic aneurysm—In search of an optimal differential diagnosis". Journal of Cardiology. 59 (2): 123–131. doi:10.1016/j.jjcc.2011.10.006. ISSN 0914-5087. PMID 22218322. 3. ^ a b c d e "Aortic Aneurysm: Causes, Symptoms, Treatments, and More." WebMD. WebMD, n.d. Web. 22 July 2015. 4. ^ a b "Abdominal Aortic Aneurysm: Diagnosis and Management." SpringerReference (2011): n. pag. Web. 5. ^ Iino M, Kuribayashi S, Imakita S, Takamiya M, Matsuo H, Ookita Y, Ando M, Ueda H (2002). "Sensitivity and specificity of CT in the diagnosis of inflammatory abdominal aortic aneurysms". J Comput Assist Tomogr. 26 (6): 1006–12. doi:10.1097/00004728-200211000-00026. PMID 12488751. 6. ^ Both M, Ahmadi-Simab K, Reuter M, Dourvos O, Fritzer E, Ullrich S, Gross WL, Heller M, Bähre M (July 2008). "MRI and FDG-PET in the assessment of inflammatory aortic arch syndrome in complicated courses of giant cell arteritis". Ann. Rheum. Dis. 67 (7): 1030–3. doi:10.1136/ard.2007.082123. PMID 18223265. 7. ^ Arnaoutoglou E, Kouvelos G, Koutsoumpelis A, Patelis N, Lazaris A, Matsagkas M (2015). "An Update on the Inflammatory Response after Endovascular Repair for Abdominal Aortic Aneurysm". Mediators Inflamm. 2015: 945035. doi:10.1155/2015/945035. PMC 4488540. PMID 26166953. * v * t * e Cardiovascular disease (vessels) Arteries, arterioles and capillaries Inflammation * Arteritis * Aortitis * Buerger's disease Peripheral artery disease Arteriosclerosis * Atherosclerosis * Foam cell * Fatty streak * Atheroma * Intermittent claudication * Critical limb ischemia * Monckeberg's arteriosclerosis * Arteriolosclerosis * Hyaline * Hyperplastic * Cholesterol * LDL * Oxycholesterol * Trans fat Stenosis * Carotid artery stenosis * Renal artery stenosis Other * Aortoiliac occlusive disease * Degos disease * Erythromelalgia * Fibromuscular dysplasia * Raynaud's phenomenon Aneurysm / dissection / pseudoaneurysm * torso: Aortic aneurysm * Abdominal aortic aneurysm * Thoracic aortic aneurysm * Aneurysm of sinus of Valsalva * Aortic dissection * Aortic rupture * Coronary artery aneurysm * head / neck * Intracranial aneurysm * Intracranial berry aneurysm * Carotid artery dissection * Vertebral artery dissection * Familial aortic dissection Vascular malformation * Arteriovenous fistula * Arteriovenous malformation * Telangiectasia * Hereditary hemorrhagic telangiectasia Vascular nevus * Cherry hemangioma * Halo nevus * Spider angioma Veins Inflammation * Phlebitis Venous thrombosis / Thrombophlebitis * primarily lower limb * Deep vein thrombosis * abdomen * Hepatic veno-occlusive disease * Budd–Chiari syndrome * May–Thurner syndrome * Portal vein thrombosis * Renal vein thrombosis * upper limb / torso * Mondor's disease * Paget–Schroetter disease * head * Cerebral venous sinus thrombosis * Post-thrombotic syndrome Varicose veins * Gastric varices * Portacaval anastomosis * Caput medusae * Esophageal varices * Hemorrhoid * Varicocele Other * Chronic venous insufficiency * Chronic cerebrospinal venous insufficiency * Superior vena cava syndrome * Inferior vena cava syndrome * Venous ulcer Arteries or veins * Angiopathy * Macroangiopathy * Microangiopathy * Embolism * Pulmonary embolism * Cholesterol embolism * Paradoxical embolism * Thrombosis * Vasculitis Blood pressure Hypertension * Hypertensive heart disease * Hypertensive emergency * Hypertensive nephropathy * Essential hypertension * Secondary hypertension * Renovascular hypertension * Benign hypertension * Pulmonary hypertension * Systolic hypertension * White coat hypertension Hypotension * Orthostatic hypotension [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Inflammatory aortic aneurysm	None	27,087	wikipedia	https://en.wikipedia.org/wiki/Inflammatory_aortic_aneurysm	2021-01-18T18:49:57	{"wikidata": ["Q25339466"]}
Actinomycosis A man with actinomycosis on the right side of his face SpecialtyInfectious disease Actinomycosis is a rare infectious bacterial disease caused by Actinomyces species.[1] About 70% of infections are due to either Actinomyces israelii or A. gerencseriae.[1] Infection can also be caused by other Actinomyces species, as well as Propionibacterium propionicus, which presents similar symptoms. The condition is likely to be polymicrobial aerobic anaerobic infection.[2] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 4 Treatment * 5 Epidemiology * 6 History * 7 Other animals * 8 References * 9 Further reading * 10 External links ## Signs and symptoms[edit] The disease is characterised by the formation of painful abscesses in the mouth, lungs,[3][4] breast,[5] or gastrointestinal tract.[2] Actinomycosis abscesses grow larger as the disease progresses, often over months. In severe cases, they may penetrate the surrounding bone and muscle to the skin, where they break open and leak large amounts of pus, which often contains characteristic granules (sulfur granules) filled with progeny bacteria. These granules are named due to their appearance, but are not actually composed of sulfur.[citation needed] ## Causes[edit] Actinomycosis Grocott's stain Actinomycosis Gram stain Actinomycosis is primarily caused by any of several members of the bacterial genus Actinomyces. These bacteria are generally anaerobes.[6] In animals, they normally live in the small spaces between the teeth and gums, causing infection only when they can multiply freely in anoxic environments. An affected human often has recently had dental work, poor oral hygiene, periodontal disease, radiation therapy, or trauma (broken jaw) causing local tissue damage to the oral mucosa, all of which predispose the person to developing actinomycosis. A. israelii is a normal commensal species part of the microbiota species of the lower reproductive tract of women.[7] They are also normal commensals among the gut flora of the caecum; thus, abdominal actinomycosis can occur following removal of the appendix. The three most common sites of infection are decayed teeth, the lungs, and the intestines. Actinomycosis does not occur in isolation from other bacteria. This infection depends on other bacteria (Gram-positive, Gram-negative, and cocci) to aid in invasion of tissue. * * * * * ## Diagnosis[edit] The diagnosis of actinomycosis can be a difficult one to make. In addition to microbiological examinations, magnetic resonance imaging and immunoassays may be helpful.[8] ## Treatment[edit] Actinomyces bacteria are generally sensitive to penicillin, which is frequently used to treat actinomycosis. In cases of penicillin allergy, doxycycline is used. Sulfonamides such as sulfamethoxazole may be used as an alternative regimen at a total daily dosage of 2-4 grams. Response to therapy is slow and may take months. Hyperbaric oxygen therapy may also be used as an adjunct to conventional therapy when the disease process is refractory to antibiotics and surgical treatment.[9][10] ## Epidemiology[edit] Disease incidence is greater in males between the ages of 20 and 60 years than in females.[11] Before antibiotic treatments became available, the incidence in the Netherlands and Germany was one per 100,000 people/year. Incidence in the U.S. in the 1970s was one per 300,000 people/year, while in Germany in 1984, it was estimated to be one per 40,000 people/year.[11] The use of intrauterine devices (IUDs) has increased incidence of genitourinary actinomycosis in females. Incidence of oral actinomycosis, which is harder to diagnose, has increased.[11] ## History[edit] In 1877, pathologist Otto Bollinger described the presence of A. bovis in cattle, and shortly afterwards, James Israel discovered A. israelii in humans. In 1890, Eugen Bostroem isolated the causative organism from a culture of grain, grasses, and soil. After Bostroem's discovery, a general misconception existed that actinomycosis was a mycosis that affected individuals who chewed grass or straw. The pathogen is still known as the “great masquerader".[12] Bergey's Manual of Systematic Bacteriology classified the organism as bacterial in 1939,[13] but the disease remained classified as a fungus in the 1955 edition of the Control of Communicable Diseases in Man.[14] Violinist Joseph Joachim died of actinomycosis on 15 August 1907. The Norwegian painter Halfdan Egedius died from actinomycosis on 2 February 1899. ## Other animals[edit] Main article: Actinomycosis in animals Actinomycosis occurs rarely in humans, but rather frequently in cattle as a disease called "lumpy jaw". This name refers to the large abscesses that grow on the head and neck of the infected animal. It can also affect swine, horses, and dogs, and less often wild animals and sheep. ## References[edit] 1. ^ a b Valour F, Sénéchal A, Dupieux C, Karsenty J, Lustig S, Breton P, Gleizal A, Boussel L, Laurent F, Braun E, Chidiac C, Ader F, Ferry T (2014). "Actinomycosis: etiology, clinical features, diagnosis, treatment, and management". Infect Drug Resist. 7: 183–97. doi:10.2147/IDR.S39601. PMC 4094581. PMID 25045274. 2. ^ a b Bowden GHW (1996). Baron S; et al. (eds.). Actinomycosis in: Baron's Medical Microbiology (4th ed.). Univ of Texas Medical Branch. ISBN 978-0-9631172-1-2. (via NCBI Bookshelf). 3. ^ Brook, I (Oct 2008). "Actinomycosis: diagnosis and management". Southern Medical Journal. 101 (10): 1019–23. doi:10.1097/SMJ.0b013e3181864c1f. PMID 18791528. S2CID 19554893. 4. ^ Mabeza, GF; Macfarlane J (March 2003). "Pulmonary actinomycosis". European Respiratory Journal. 21 (3): 545–551. doi:10.1183/09031936.03.00089103. PMID 12662015. 5. ^ Abdulrahman, Ganiy Opeyemi; Gateley, Christopher Alan (1 January 2015). "Primary actinomycosis of the breast caused by Actinomyces turicensis with associated Peptoniphilus harei". Breast Disease. 35 (1): 45–47. doi:10.3233/BD-140381. PMID 25095985. 6. ^ Ryan KJ; Ray CG, eds. (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. ISBN 978-0-8385-8529-0. 7. ^ Hoffman, Barbara (2012). Williams gynecology (2nd ed.). New York: McGraw-Hill Medical. p. 42. ISBN 978-0071716727. 8. ^ Böhm, Ingrid; Willinek, Winfried; Schild, Hans H. (October 2006). "Magnetic Resonance Imaging Meets Immunology: An Unusual Combination of Diagnostic Tools Leads to the Diagnosis Actinomycosis". The American Journal of Gastroenterology. 101 (10): 2439–2440. PMID 17032212. 9. ^ "Bone Infections". MedlinePlus. US National Library of Medicine. Retrieved 16 August 2015. 10. ^ "Osteomyelitis (Refractory)". Undersea and Hyperbaric Medical Society. Retrieved 16 August 2015. 11. ^ a b c Wolff K, Goldsmith LA, Katz S, Gilchrist BA, Paller A, Leffell DJ (2007). Fitzpatrick's Dermatology in General Medicine (7th ed.). McGraw Hill. 12. ^ Sullivan, D. C.; Chapman, S. W. (12 May 2010). "Bacteria That Masquerade as Fungi: Actinomycosis/Nocardia". Proceedings of the American Thoracic Society. 7 (3): 216–221. doi:10.1513/pats.200907-077AL. PMID 20463251. 13. ^ Strong, Richard (1944). Stitt's Diagnosis, Prevention and Treatment of Tropical Diseases (7th ed.). p. 1182. 14. ^ Control of Communicable Diseases in Man (8th ed.). American Public Health Association. 1955. ## Further reading[edit] * Anderson, Clifton W.; Jenkins, Ralph H. (December 15, 1938). "Actinomycosis of the Scrotum". New England Journal of Medicine. 219 (24): 953–954. doi:10.1056/NEJM193812152192403. * Codman, E. A. (August 11, 1898). "A Case of Actinomycosis". The Boston Medical and Surgical Journal. 139 (6): 134–135. doi:10.1056/NEJM189808111390606. * Randolph HL Wong; Alan DL Sihoe; KH Thung; Innes YP Wan; Margaret BY Ip; Anthony PC Yim (June 2004). "Actinomycosis: an often forgotten diagnosis". Asian Cardiovasc Thorac Ann. 12 (2): 165–7. doi:10.1177/021849230401200218. PMID 15213087. S2CID 9930882. Review * Munro, John C. (September 13, 1900). "Four Cases of Actinomycosis". The Boston Medical and Surgical Journal. 143 (11): 255–256. doi:10.1056/NEJM190009131431103. * Whitney, W. F. (June 5, 1884). "A Case of Actinomycosis in a Heifer". The Boston Medical and Surgical Journal. 110 (23): 532. doi:10.1056/NEJM188406051102302. ## External links[edit] Classification D * ICD-10: A42 * ICD-9-CM: 039 * MeSH: D000196 * DiseasesDB: 145 External resources * MedlinePlus: 000599 * eMedicine: med/31 * Patient UK: Actinomycosis * v * t * e Gram-positive bacterial infection: Actinobacteria Actinomycineae Actinomycetaceae * Actinomyces israelii * Actinomycosis * Cutaneous actinomycosis * Tropheryma whipplei * Whipple's disease * Arcanobacterium haemolyticum * Arcanobacterium haemolyticum infection * Actinomyces gerencseriae Propionibacteriaceae * Propionibacterium acnes Corynebacterineae Mycobacteriaceae M. tuberculosis/ M. bovis * Tuberculosis: Ghon focus/Ghon's complex * Pott disease * brain * Meningitis * Rich focus * Tuberculous lymphadenitis * Tuberculous cervical lymphadenitis * cutaneous * Scrofuloderma * Erythema induratum * Lupus vulgaris * Prosector's wart * Tuberculosis cutis orificialis * Tuberculous cellulitis * Tuberculous gumma * Lichen scrofulosorum * Tuberculid * Papulonecrotic tuberculid * Primary inoculation tuberculosis * Miliary * Tuberculous pericarditis * Urogenital tuberculosis * Multi-drug-resistant tuberculosis * Extensively drug-resistant tuberculosis M. leprae * Leprosy: Tuberculoid leprosy * Borderline tuberculoid leprosy * Borderline leprosy * Borderline lepromatous leprosy * Lepromatous leprosy * Histoid leprosy Nontuberculous R1: * M. kansasii * M. marinum * Aquarium granuloma R2: * M. gordonae R3: * M. avium complex/Mycobacterium avium/Mycobacterium intracellulare/MAP * MAI infection * M. ulcerans * Buruli ulcer * M. haemophilum R4/RG: * M. fortuitum * M. chelonae * M. abscessus Nocardiaceae * Nocardia asteroides/Nocardia brasiliensis/Nocardia farcinica * Nocardiosis * Rhodococcus equi Corynebacteriaceae * Corynebacterium diphtheriae * Diphtheria * Corynebacterium minutissimum * Erythrasma * Corynebacterium jeikeium * Group JK corynebacterium sepsis Bifidobacteriaceae * Gardnerella vaginalis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Actinomycosis	c0001261	27,088	wikipedia	https://en.wikipedia.org/wiki/Actinomycosis	2021-01-18T18:33:28	{"gard": ["5728"], "mesh": ["D000196"], "umls": ["C0001261"], "orphanet": ["457095"], "wikidata": ["Q422268"]}
Aminolevulinic acid dehydratase deficiency porphyria Other namesPorphyria due to ALA dehydratase deficiency ALA dehydratase deficiency has an autosomal recessive pattern of inheritance. SpecialtyGastroenterology, dermatology, medical genetics, endocrinology Aminolevulinic acid dehydratase deficiency porphyria (also known as "Doss porphyria",[1] "plumboporphyria",[1] or "ADP"[2]) is a rare autosomal recessive metabolic disorder that results from inappropriately low levels of the enzyme delta-aminolevulinic acid dehydratase (ALAD), which is required for normal heme synthesis. This deficiency results in the accumulation of a toxic metabolic precursor in the heme synthesis pathway called aminolevulinic acid (ALA). [2] Heme is a component of hemoglobin which carries oxygen in red blood cells. ALA dehydratase deficiency is a rare cause of hepatic porphyria, meaning that excess porphyrins originate from the liver rather than the bone marrow as in erythropoietic porphyrias.[3][4] ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Diagnosis * 4 Treatment * 5 Prevalence * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] The clinical presentation of ADP includes a wide range of neurologic and gastrointestinal symptoms.[2] The severity of symptoms is dependent on how functional the ALAD enzyme is in each person. The higher the enzyme activity, the fewer symptoms a person will exhibit and the later they will present. The less functional a persons ALAD enzyme is, the earlier they will present and the more severe their symptoms will be. The disease can present during early childhood (as well as in adulthood) with acute neurologic symptoms that resemble those encountered in acute intermittent porphyria.[1] Patients can also have gastrointestinal symptoms during acute attacks, including abdominal cramping, vomiting, and constipation.[2] Gastrointestinal symptoms can result in failure to thrive and poor weight gain in children. Other symptoms that can occur during an acute attack include a rapid heart beat, high blood pressure, and respiratory difficulties.[2] Acute attacks can last for weeks and are also called "neurovisceral" attacks due to the neurological complications associated. Patients have reported numbness and tingling in the extremities, seizures, burning pain, poor coordination, inability to move muscles voluntarily, and psychological disturbances.[2] Psychosis, though rare, has occurred in severe instances. Many triggers have been identified for acute ADP attacks including fasting, a low carb diet, dehydration, alcohol intake, the use of estrogen or progesterone, certain drugs, and other mental and physical stressors.[2] ## Genetics[edit] ALA dehydratase deficiency is inherited in an autosomal recessive manner.[3] This means a defective gene responsible for the disorder is located on an autosome, and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder. In conditions where both parents are carriers: * The risk of having a child with ADP is 25% for each pregnancy.[5] * The risk of having a child who is also a carrier is 50%.[5] * The chance of having a child who is unaffected and is not a carrier is 25%.[5] ## Diagnosis[edit] This section is empty. You can help by adding to it. (August 2017) To make a diagnosis, the relevant presenting symptoms and a detailed patient history must be considered in addition to obtaining biomarkers in the urine or blood. These biomarkers include urine porphobilinogen (PBG), aminolevulinic acid (ALA), and porphyrins found in blood and urine.[2] PBG levels fluctuate and are best measured during the onset of acute symptoms.[2] ALA levels are increased in ADP and correlate with the severity of the disease.[6] If levels of porphyrins are significantly elevated, DNA testing can be performed to determine the specific mutations in the ALAD gene. [2][6] DNA analysis is the most specific test for making a diagnosis of ADP.[6] ## Treatment[edit] Supportive care and treatment of symptoms are the typical management options for ADP. During acute attacks, patients are often hospitalized and given medications for nausea/vomiting, rapid heartbeat, and hypertension while their fluid and electrolyte levels are monitored.[2] Glucose supplementation and intravenous hematin are the mainstay of treatment for acute attacks.[2] Avoiding physical and psychological stressors has been shown to limit the reoccurrence of attacks.[2][5] Specific drugs have been identified that can trigger ADP attacks. Inducers of the CYP-450 enzymes are drugs that should be discontinued or avoided in patients with ADP. Drugs included in this category are anti-convulsants like phenytoin and carbamazepine, and other drugs like barbiturates, St. John's wort, and rifampin. ## Prevalence[edit] The condition is extremely rare, with fewer than 10 cases ever reported.[7] All reported cases have been seen in males.[2] A feature of ADP that separates it from other porphyrias is that it is more prevalent in males than in females.[2] However, it theoretically affects males and females at the same rate. Most cases have been identified in Europe but it can occur in any population.[5] ## See also[edit] * List of cutaneous conditions ## References[edit] 1. ^ a b c Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 2. ^ a b c d e f g h i j k l m n o "ALAD-Deficiency Porphyria (ADP)". American Porphyria Foundation. Retrieved 2020-06-29. 3. ^ a b Jaffe EK, Stith L (February 2007). "ALAD porphyria is a conformational disease". American Journal of Human Genetics. 80 (2): 329–37. doi:10.1086/511444. PMC 1785348. PMID 17236137. 4. ^ Doss M, von Tiepermann R, Schneider J, Schmid H (October 1979). "New type of hepatic porphyria with porphobilinogen synthase defect and intermittent acute clinical manifestation". Klinische Wochenschrift. 57 (20): 1123–7. doi:10.1007/bf01481493. PMID 513604. 5. ^ a b c d e "ALAD Porphyria". NORD (National Organization for Rare Disorders). Retrieved 2020-06-29. 6. ^ a b c "ALA Dehydratase Deficiency Porphyria Workup: Laboratory Studies, Other Tests". emedicine.medscape.com. Retrieved 2020-06-29. 7. ^ Overview of the Porphyrias Archived 2011-07-22 at the Wayback Machine at The Porphyrias Consortium (a part of NIH Rare Diseases Clinical Research Network (RDCRN)) Retrieved June 2011 ## External links[edit] Classification D * ICD-10: E80.2 * OMIM: 612740 External resources * Orphanet: 100924 * v * t * e Heme metabolism disorders Porphyria, hepatic and erythropoietic (porphyrin) early mitochondrial: * ALAD porphyria * Acute intermittent porphyria cytoplasmic: * Gunther disease/congenital erythropoietic porphyria * Porphyria cutanea tarda/Hepatoerythropoietic porphyria late mitochondrial: * Hereditary coproporphyria * Harderoporphyria * Variegate porphyria * Erythropoietic protoporphyria Hereditary hyperbilirubinemia (bilirubin) unconjugated: * Gilbert's syndrome * Crigler–Najjar syndrome * Lucey–Driscoll syndrome conjugated: * Dubin–Johnson syndrome nd sheet * Rotor syndrome This dermatology article is a stub. You can help Wikipedia by expanding it. * v * t * e This genetic disorder article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Aminolevulinic acid dehydratase deficiency porphyria	c0162533	27,089	wikipedia	https://en.wikipedia.org/wiki/Aminolevulinic_acid_dehydratase_deficiency_porphyria	2021-01-18T18:56:51	{"mesh": ["D017094"], "umls": ["C0162533"], "icd-9": ["277.1"], "icd-10": ["E80.2"], "orphanet": ["100924"], "wikidata": ["Q419897"]}
The dawn phenomenon, sometimes called the dawn effect, is an observed increase in blood sugar (glucose) levels that takes place in the early-morning, often between 2 a.m. and 8 a.m. First described by Schmidt in 1981 as an increase of blood glucose or insulin demand occurring at dawn,[1] this naturally occurring phenomenon is frequently seen among the general population and is clinically relevant for patients with diabetes as it can affect their medical management. In contrast to Chronic Somogyi rebound, the dawn phenomenon is not associated with nocturnal hypoglycemia. ## Contents * 1 Physiology * 2 Treatment * 3 See also * 4 References * 5 External links ## Physiology[edit] Although not yet completely understood, the dawn phenomenon is thought to be caused by an exaggeration of the normal physiologic hormonal processes that occur overnight. Overnight the human body sees increased levels of several hormones, most notably growth hormone and catecholamines, that lead to increased rates of glucose production and release from the liver. These hormones also inhibit the effects of insulin, leading to an overall increase in circulating blood glucose.[2] This effect is amplified in patients with islet β-cell dysfunction such as diabetics.[3] Notably throughout this process glucagon levels remain unchanged and the increased levels of cortisol observed overnight do not appear to be involved.[4][5] Observed hyperglycemia secondary to the dawn phenomenon is often defined as an increase in blood glucose of at least >1.1mmol/L (20mg/dL) between the lowest level at night and the highest level before breakfast; however, actual ranges may vary.[3][6] The physiologic process involved in causing the dawn phenomenon has been shown to occur in most people. In non-diabetic patients there is a modest increase in insulin secretion just before dawn which compensates for the increased glucose being released from the liver to prevent hyperglycemia. However, studies have shown that diabetic patients fail to compensate for this transiently increased blood glucose release, resulting in hyperglycemia. This resulting hyperglycemia is clinically relevant in diabetic patients as its lasting effects can lead to overall poor glycemic control. In Type 1 diabetics hyperglycemia due to the dawn phenomenon can persist despite adequate insulin compensation overnight, while in Type 2 diabetics the dawn phenomenon has been shown to be resistant to treatment with both oral medications and diet modifications. [6][7][8] An "extended" dawn phenomenon has also been observed in which the abnormal increase in blood glucose levels continues after breakfast. This prolonged duration is thought to be caused by the compounding effects of absorbing and metabolizing breakfast carbohydrates during this period. Both the dawn phenomenon and its extended period have been shown to be significantly more difficult to control when a patient's HbA1c is greater than 7%.[8][7] ## Treatment[edit] Management of the dawn phenomenon varies by patient and thus should be done with regular assistance from a patient's physician. Some treatment options include, but are not limited to, dietary modifications, increased exercise before breakfast and during the evening, and oral anti-hyperglycemic medications if a patient's HbA1c is > 7%.[3][7][9] Insulin pumps can also be used to provide continuous subcutaneous infusions and are regarded as the gold standard for managing the dawn phenomenon in type 1 diabetics.[10] ## See also[edit] * Cortisol awakening response ## References[edit] 1. ^ Schmidt, M. I.; Hadji-Georgopoulos, A.; Rendell, M.; Margolis, S.; Kowarski, A. (1981-11-01). "The Dawn Phenomenon, an Early Morning Glucose Rise: Implications for Diabetic Intraday Blood Glucose Variation". Diabetes Care. 4 (6): 579–585. doi:10.2337/diacare.4.6.579. ISSN 0149-5992. PMID 6751733. S2CID 13046401. 2. ^ Campbell, Peter J.; Bolli, Geremia B.; Cryer, Philip E.; Gerich, John E. (1985-06-06). "Pathogenesis of the Dawn Phenomenon in Patients with Insulin-Dependent Diabetes Mellitus". New England Journal of Medicine. 312 (23): 1473–1479. doi:10.1056/NEJM198506063122302. ISSN 0028-4793. PMID 2859524. 3. ^ a b c Zheng, Xin; Qi, Yanyan; Bi, Lina; Shi, Wenli; Zhang, Yan; Zhao, Dan; Hu, Su; Li, Meixin; Li, Qin (2020). "Effects of Exercise on Blood Glucose and Glycemic Variability in Type 2 Diabetic Patients with Dawn Phenomenon". BioMed Research International. 2020: 1–6. doi:10.1155/2020/6408724. PMC 7057022. PMID 32149118. 4. ^ Bright, G. M.; Melton, T. W.; Rogol, A. D.; Clarke, W. L. (1980-08-01). "Failure of Cortisol Blockade to Inhibit Early Morning Increases in Basal Insulin Requirements in Fasting Insulin-dependent Diabetics". Diabetes. 29 (8): 662–664. doi:10.2337/diab.29.8.662. ISSN 0012-1797. PMID 7002678. 5. ^ Skor, D. A.; White, N. H.; Thomas, L.; Shah, S. D.; Cryer, P. E.; Santiago, J. V. (1983-05-01). "Examination of the role of the pituitary-adrenocortical axis, counterregulatory hormones, and insulin clearance in variable nocturnal insulin requirements in insulin-dependent diabetes". Diabetes. 32 (5): 403–407. doi:10.2337/diabetes.32.5.403. ISSN 0012-1797. PMID 6341122. 6. ^ a b Porcellati, F.; Lucidi, P.; Bolli, G. B.; Fanelli, C. G. (2013-11-21). "Thirty Years of Research on the Dawn Phenomenon: Lessons to Optimize Blood Glucose Control in Diabetes". Diabetes Care. 36 (12): 3860–3862. doi:10.2337/dc13-2088. ISSN 0149-5992. PMC 3836156. PMID 24265365. 7. ^ a b c Monnier, L.; Colette, C.; Dunseath, G. J.; Owens, D. R. (2007-01-26). "The Loss of Postprandial Glycemic Control Precedes Stepwise Deterioration of Fasting With Worsening Diabetes". Diabetes Care. 30 (2): 263–269. doi:10.2337/dc06-1612. ISSN 0149-5992. PMID 17259492. 8. ^ a b Carr, Richard D.; Alexander, Charles M. (2014-06-24). "Comment on Monnier et al. Magnitude of the Dawn Phenomenon and Its Impact on the Overall Glucose Exposure in Type 2 Diabetes: Is This of Concern? Diabetes Care 2013;36:4057–4062". Diabetes Care. 37 (7): e161–e162. doi:10.2337/dc14-0352. ISSN 0149-5992. PMID 24963116. 9. ^ Rybicka, Malwina. (2011). "The dawn phenomenon and the Somogyi effect : two phenomena of morning hyperglycaemia". Endokrynologia Polska. 62 (3): 276–84. OCLC 998912305. PMID 21717414. 10. ^ Janež, Andrej; Guja, Cristian; Mitrakou, Asimina; Lalic, Nebojsa; Tankova, Tsvetalina; Czupryniak, Leszek; Tabák, Adam G.; Prazny, Martin; Martinka, Emil; Smircic-Duvnjak, Lea (2020-01-04). "Insulin Therapy in Adults with Type 1 Diabetes Mellitus: a Narrative Review". Diabetes Therapy. 11 (2): 387–409. doi:10.1007/s13300-019-00743-7. ISSN 1869-6953. PMC 6995794. PMID 31902063. ## External links[edit] * Mayo Clinic - The 'dawn phenomenon': What causes it? * Diabetes Self Management - Dawn Phenomenon * Dawn Phenomenon (Liver Dump) * Spiritual and scientific benefits of waking up before Dawn [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Dawn phenomenon	c0342314	27,090	wikipedia	https://en.wikipedia.org/wiki/Dawn_phenomenon	2021-01-18T18:50:04	{"umls": ["C0342314"], "wikidata": ["Q1178748"]}
Tropical endomyocardial fibrosis is a restrictive cardiopathy, occuring almost exclusively in children and young adults in tropical and subtropical regions, characterized by endocardial fibrosis, affecting the apices and the inflow tract of the right or left ventricle (or both) and manifesting with a restrictive cardimyopathy and atrioventricular regurgitation leading to severe pulmonary hypertension, very high systemic venous pressure and congestive cardiac failure. Suspected etiologies include helminth and protozoal infestation and malnutrition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Tropical endomyocardial fibrosis	c2882252	27,091	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=75565	2021-01-23T19:03:26	{"icd-10": ["I42.3"], "synonyms": ["Davies disease", "TEMF"]}
A number sign (#) is used with this entry because Fanconi renotubular syndrome-4 with maturity-onset diabetes of the young (FRTS4) is caused by heterozygous mutation in the HNF4A gene (600281) on chromosome 20q13. Heterozygous mutation in the HNF4A gene can also cause isolated MODY1 (125850). For a general phenotypic description and a discussion of genetic heterogeneity of Fanconi renotubular syndrome, see FRTS1 (134600). Clinical Features Stanescu et al. (2012) reported a female infant who presented with macrosomia and severe hypoglycemia associated with hyperinsulinism in the first hours of life. Over the following years, she required lower doses to maintain normoglycemia, and treatment was discontinued at age 4 years. By age 1 year, she had also developed radiologic evidence of rickets, increased plasma alkaline phosphatase, decreased phosphorus, glycosuria, proteinuria, and metabolic acidosis. These features were reminiscent of the Fanconi-Bickel syndrome (227810). The child also had hepatomegaly with elevated transaminases; liver biopsy showed abundant cytoplasmic glycogen with mild portal inflammation and fibrosis. Hamilton et al. (2014) reported 2 sisters with neonatal hypoglycemia associated with hyperinsulinism and macrosomia. Both were diagnosed with Fanconi renotubular syndrome and nephrocalcinosis resulting in short stature and rickets. One sister had a similarly affected son. The renal phenotype was manifest as low molecular weight proteinuria, aminoaciduria, glycosuria, phosphaturia, calciuria, and low serum urate. Three additional unrelated patients with a similar disorder were subsequently identified; 2 of these patients developed diabetes mellitus at ages 20 and 12 years, respectively. Inheritance The transmission pattern of FRTS4 in the families with MODY reported by Hamilton et al. (2014) was consistent with autosomal dominant inheritance. Molecular Genetics In a girl with Fanconi renotubular syndrome with MODY, Stanescu et al. (2012) identified a de novo heterozygous missense mutation in the HNF4A gene (R76W; 600281.0008). Hamilton et al. (2014) identified a heterozygous R76W mutation in 3 members of a family with FRTS4 and a pancreatic beta-cell phenotype manifest as macrosomia and neonatal hypoglycemia associated with hyperinsulinemia. Three additional unrelated carriers of the heterozygous R76W mutation were subsequently identified from a cohort of 147 probands with HNF4A mutations; all had the Fanconi renal phenotype with nephrocalcinosis. The R76W mutation, which occurs in the DNA-binding domain, was hypothesized to cause defective interaction with major regulatory genes; however, functional studies were not performed. Analysis of urine and serum samples from 20 diabetic patients with other HNF4A mutations showed no evidence of a Fanconi renal phenotype. Hamilton et al. (2014) concluded that this specific mutation is associated with a unique phenotype comprising both MODY and FRTS. INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature Weight \- Increased birth weight Other \- Macrosomia, neonatal ABDOMEN Liver \- Hepatomegaly (1 patient) GENITOURINARY Kidneys \- Renal proximal tubule defect \- Nephrocalcinosis SKELETAL \- Rickets METABOLIC FEATURES \- Metabolic acidosis due to renal bicarbonate loss ENDOCRINE FEATURES \- Hypoglycemia, neonatal \- Hyperinsulinism \- Diabetes mellitus (in some patients) LABORATORY ABNORMALITIES \- Glycosuria \- Low molecular weight proteinuria \- Aminoaciduria \- Phosphaturia \- Calciuria \- Hypouricemia MISCELLANEOUS \- Onset of hypoglycemia and hyperinsulinism in the neonatal period \- Onset of renal dysfunction in early childhood \- Some patients develop diabetes mellitus as adolescents MOLECULAR BASIS \- Caused by mutation in the hepatocyte nuclear factor 4-alpha gene (HNF4A, 600281.0008 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	FANCONI RENOTUBULAR SYNDROME 4 WITH MATURITY-ONSET DIABETES OF THE YOUNG	c0431693	27,092	omim	https://www.omim.org/entry/616026	2019-09-22T15:50:14	{"mesh": ["C535520"], "omim": ["616026"], "orphanet": ["93111"], "synonyms": ["Alternative titles", "FRTS4 WITH MODY"]}
Tsukahara et al. (1986) described 2 Japanese sisters with ataxia-telangiectasia that had typical clinical and laboratory features except for marked generalized skin pigmentation and unusually early death (at 15 months in the first born). Skin pigmentation was already present at 3 months of age in the first born and appeared at 7 months in the second affected child. Autopsy of the older child provided no obvious explanation for the hyperpigmentation. The anterior pituitary was described as containing 'occasional cells with large hyperchromic, bizarre or doughnut-shaped nuclei.' Limbs \- Flexion-extension finger contractures Eye \- Telangiectasia, conjunctival Inheritance \- Autosomal recessive Thymus \- Hypoplasia Immune \- IgA deficiency \- Anergy to skin testing Neuro \- Cerebral ataxia \- Oculomotor apraxia \- Dystonia Muscle \- Progressive spinal muscular atrophy \- Interosseous muscular atrophy Metabolic \- Glucose tolerance decreased Misc \- Sinopulmonary infection \- Strong predisposition to malignancy, esp. 14q+ leukemia \- Sensitivity to x-ray \- Increased cancer risk in heterozygotes Lab \- Chromosome breakage \- Phytohemagglutinin response impaired \- Serum alpha-fetoprotein increased Growth \- Death in infancy Skin \- Telangiectasia, facial \- Hyperpigmentation, marked generalized ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	ATAXIA-TELANGIECTASIA WITH GENERALIZED SKIN PIGMENTATION AND EARLY DEATH	c0004135	27,093	omim	https://www.omim.org/entry/208910	2019-09-22T16:30:38	{"mesh": ["D001260"], "omim": ["208910"], "orphanet": ["100"]}
A number sign (#) is used with this entry because of evidence that short stature, optic nerve atrophy, and Pelger-Huet anomaly (SOPH syndrome) is caused by homozygous mutation in the NBAS gene (608025) on chromosome 2p24. Description Among the Yakuts, an Asian population isolate that is located in the northeastern part of Siberia, Maksimova et al. (2010) ascertained a short stature syndrome involving autosomal recessive postnatal growth failure, small hands and feet, loss of visual acuity with abnormalities of color vision, abnormal nuclear shape in neutrophil granulocytes (Pelger-Huet anomaly; see 169400), and normal intelligence. Clinical Features In the linguistically and geographically isolated Yakut population of northeastern Siberia, previously studied for the presence of autosomal dominant and recessive as well as X-linked recessive genetic diseases (Nogovitsina et al., 1999; Tarskaia et al., 2003; Tarskaia et al., 2004), Maksimova et al. (2010) ascertained 34 Yakut patients, 22 female and 12 male, all of whom had postnatal growth failure, loose and senile skin with depressed turgor of tissue, micromelia, brachydactyly, and bilateral optic nerve atrophy with nonprogressive loss of visual acuity, associated with complete or incomplete achromatopsia (color blindness). In addition, all of the patients who underwent hematologic examination (22 patients from 21 families) had a high frequency of hypolobulation of granulocyte nuclei, characteristic of Pelger-Huet anomaly. Features seen in at least 28 (82%) of the 34 patients included a brachycephalic skull with hypoplasia of the frontal and parietal tubers and narrow forehead, long senile face with small features, small orbits, bilateral exophthalmos, hypoplastic cheekbones, straight nose with prominent glabella, long philtrum, thin lips, high voice with harsh timber, short neck, hypermobility of small joints, muscular hypotonia, and wide feet with high arch. Other commonly seen features included fine hair, facial asymmetry, thick and/or bushy eyebrows, epicanthus, sandal gap, and wide big toes. All but 1 of the patients had normal intellectual function. Maksimova et al. (2010) designated the phenotype 'SOPH syndrome,' for short stature, optic atrophy, and Pelger-Huet anomaly. Mapping In 33 Yakut patients with SOPH syndrome, who were known to be negative for mutation in the CUL7 gene (609577), which can result in Yakut short stature syndrome (see 273750), Maksimova et al. (2010) performed genomewide homozygosity mapping followed by fine mapping that narrowed the critical interval to a 1.1-Mb segment between the dinucleotide polymorphic markers M1491 and M1599 on chromosome 2p24.3. Molecular Genetics In 33 Yakut patients from 30 families with short stature, optic nerve atrophy, and Pelger-Huet anomaly (SOPH syndrome) mapping to chromosome 2p24.3, Maksimova et al. (2010) analyzed 2 candidate genes and identified homozygosity for a missense mutation in the NBAS gene (R1914H; 608025.0001) that segregated with disease. None of 203 Yakut controls carried the mutation in homozygous state, and the mutation was not found in 100 Japanese controls. Because in cases of autosomal dominantly inherited Pelger-Huet anomaly (169400) caused by mutation in the LBR gene (600024), the amount of LBR quantitatively affects lobulation of neutrophilic nuclei, Maksimova et al. (2010) analyzed neutrophils from a patient with SOPH syndrome and a control, but found LBR expression to be comparable between the 2 individuals. INHERITANCE \- Autosomal recessive GROWTH Height \- Postnatal growth failure HEAD & NECK Head \- Brachycephaly Face \- Long face \- Senile-appearing face \- Narrow forehead \- Prominent glabella \- Hypoplastic cheekbones \- Small facial features \- Facial asymmetry \- Long philtrum Eyes \- Thick eyebrows \- Bushy eyebrows \- Small orbits \- Exophthalmos, bilateral \- Epicanthus \- Optic nerve atrophy, bilateral \- Decreased visual acuity, nonprogressive \- Achromatopsia, complete or incomplete \- Myopia (in some patients) \- Strabismus (in some patients) \- Hypertelorism (in some patients) \- Hypermetropia (rare) \- Pigmented nevus (rare) Nose \- Straight nose Mouth \- Thin lips Neck \- Short neck GENITOURINARY Internal Genitalia (Female) \- Uterine hypoplasia (in some patients) SKELETAL \- Delayed bone age (in some patients) Skull \- Brachycephaly \- Hypoplasia of frontal tubers \- Hypoplasia of parietal tubers Limbs \- Micromelia Hands \- Brachydactyly \- Hypermobility of small joints \- Simian crease (in some patients) \- Syndactyly (rare) Feet \- Brachydactyly \- Hypermobility of small joints \- Wide feet \- High arch \- Sandal gap \- Wide hallux SKIN, NAILS, & HAIR Skin \- Loose skin \- Decreased turgor of skin Hair \- Fine hair MUSCLE, SOFT TISSUES \- Muscular hypotonia NEUROLOGIC Central Nervous System \- Normal intellectual function VOICE \- High voice with harsh timber HEMATOLOGY \- Hypolobulation of granulocyte nuclei (Pelger-Huet anomaly) MOLECULAR BASIS \- Caused by mutation in the neuroblastoma-amplified sequence gene (NBAS, 608025.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	SHORT STATURE, OPTIC NERVE ATROPHY, AND PELGER-HUET ANOMALY	c3541319	27,094	omim	https://www.omim.org/entry/614800	2019-09-22T15:54:19	{"omim": ["614800"], "orphanet": ["391677"], "synonyms": ["SOPH syndrome", "Alternative titles", "SOPH SYNDROME"]}
"Tongue tied" redirects here. For other uses, see Tongue tied (disambiguation). Ankyloglossia Adult with ankyloglossia SpecialtyMedical genetics Ankyloglossia, also known as tongue-tie, is a congenital oral anomaly that may decrease the mobility of the tongue tip[1] and is caused by an unusually short, thick lingual frenulum, a membrane connecting the underside of the tongue to the floor of the mouth.[2] Ankyloglossia varies in degree of severity from mild cases characterized by mucous membrane bands to complete ankyloglossia whereby the tongue is tethered to the floor of the mouth.[2] ## Contents * 1 Presentation * 1.1 Feeding * 1.2 Speech * 1.3 Mechanical and social effects * 1.4 Tongue posture and mouth breathing * 1.5 Dental issues * 1.6 Fascia and Muscle Compensation * 2 Diagnosis * 3 Treatment * 4 References * 5 External links ## Presentation[edit] Ankyloglossia can affect eating, speech, and oral hygiene[3] as well as have mechanical/social effects.[4] Ankyloglossia can also prevent the tongue from contacting the anterior palate. This can then promote an infantile swallow and hamper the progression to an adult-like swallow which can result in an open bite deformity.[2] It can also result in mandibular prognathism; this happens when the tongue contacts the anterior portion of the mandible with exaggerated anterior thrusts.[2] Opinion varies regarding how frequently ankyloglossia truly causes problems. Some professionals believe it is rarely symptomatic, whereas others believe it is associated with a variety of problems. The disagreement among professionals was documented in a study by Messner and Lalakea (2000).[5] ### Feeding[edit] Messner et al.[6] studied ankyloglossia and infant feeding. Thirty-six infants with ankyloglossia were compared to a control group without ankyloglossia. The two groups were followed for six months to assess possible breastfeeding difficulties; defined as nipple pain lasting more than six weeks, or infant difficulty latching onto or staying onto the mother’s breast. Twenty-five percent of mothers of infants with ankyloglossia reported breastfeeding difficulty compared with only 3% of the mothers in the control group. The study concluded that ankyloglossia can adversely affect breastfeeding in certain infants. Infants with ankyloglossia do not, however, have such big difficulties when feeding from a bottle.[7] Limitations of this study include the small sample size and the fact that the quality of the mother’s breastfeeding was not assessed. Wallace and Clark also studied breastfeeding difficulties in infants with ankyloglossia.[8] They followed 10 infants with ankyloglossia who underwent surgical tongue-tie division. Eight of the ten mothers experienced poor infant latching onto the breast, 6/10 experienced sore nipples and 5/10 experienced continual feeding cycles; 3/10 mothers were exclusively breastfeeding. Following a tongue-tie division, 4/10 mothers noted immediate improvements in breastfeeding, 3/10 mothers did not notice any improvements and 6/10 mothers continued breastfeeding for at least four months after the surgery. The study concluded that tongue-tie division may be a possible benefit for infants experiencing breastfeeding difficulties due to ankyloglossia and further investigation is warranted. The limitations of this study include the small sample size and the fact that there was not a control group. In addition, the conclusions were based on subjective parent report as opposed to objective measures. ### Speech[edit] Messner and Lalakea studied speech in children with ankyloglossia. They noted that the phonemes likely to be affected due to ankyloglossia include sibilants and lingual sounds such as 'r'. In addition, the authors also state that it is uncertain as to which patients will have a speech disorder that can be linked to ankyloglossia and that there is no way to predict at a young age which patients will need treatment. The authors studied 30 children from one to 12 years of age with ankyloglossia, all of whom underwent frenuloplasty. Fifteen children underwent speech evaluation before and after surgery. Eleven patients were found to have abnormal articulation before surgery and nine of these patients were found to have improved articulation after surgery. Based on the findings, the authors concluded that it is possible for children with ankyloglossia to have normal speech in spite of decreased tongue mobility. However, according to their study, a large percentage of children with ankyloglossia will have articulation deficits that can be linked to tongue-tie and these deficits may be improved with surgery. The authors also note that ankyloglossia does not cause a delay in speech or language, but at the most, problems with enunciation. Limitations of the study include a small sample size as well as a lack of blinding of the speech-language pathologists who evaluated the subjects’ speech. Messner and Lalakea also examined speech and ankyloglossia in another study. They studied 15 patients and speech was grossly normal in all the subjects. However, half of the subjects reported that they thought that their speech was more effortful than other peoples' speech.[4] Horton and colleagues discussed the relationship between ankyloglossia and speech. They believe that the tongue-tie contributes to difficulty in range and rate of articulation and that compensation is needed. Compensation at its worst may involve a Cupid's bow of the tongue.[2] Although the tongue-tie exists, and even years following surgery, common speech abnormalities include mispronunciation of words, the most common of which is pronouncing Ls as Ws; for example, the word "lemonade" would come out as "wemonade". ### Mechanical and social effects[edit] Ankyloglossia can result in mechanical and social effects.[4] Lalakea and Messner[4] studied 15 people, aged 14 to 68 years old. The subjects were given questionnaires in order to assess functional complaints associated with ankyloglossia. Eight subjects noted one or more mechanical limitations which included cuts or discomfort underneath the tongue and difficulties with kissing, licking one’s lips, eating an ice cream cone, keeping one’s tongue clean and performing tongue tricks. In addition, seven subjects noted social effects such as embarrassment and teasing. The authors concluded that this study confirmed anecdotal evidence of mechanical problems associated with ankyloglossia and it suggests that the kinds of mechanical and social problems noted may be more prevalent than previously thought. Furthermore, the authors note that some patients may be unaware of the extent of the limitations they have due to ankyloglossia, since they have never experienced a normal tongue range of motion. A limitation of this study is the small sample size that also represented a large age range. Lalakea and Messner[9] note that mechanical and social effects may occur even without other problems related to ankyloglossia, such as speech and feeding difficulties. Also, mechanical and social effects may not arise until later in childhood, as younger children may be unable to recognize or report the effects. In addition, some problems, such as kissing, may not come about until later in life. ### Tongue posture and mouth breathing[edit] Ankyloglossia most often prohibits the tongue from resting in its ideal posture, at the roof of the mouth. When the tongue rests at the roof of the mouth, it enables nasal breathing. A seemingly unrelated consequence of ankyloglossia is chronic mouth breathing. Mouth breathing is correlated with other health issues such as enlarged tonsils and adenoids, chronic ear infections, and sleep-disordered breathing.[10][11] ### Dental issues[edit] Ankyloglossia is correlated to grinding teeth (bruxism) and temporomandibular joint (TMJ) pain. When the tongue normally rests at the roof of the mouth, it leads to the development of an ideal "U"-shaped palate. Ankyloglossia often causes a narrow, "V"-shaped palate to develop, which crowds teeth and increases the potential need for braces and possibly jaw surgery.[10][11][12] ### Fascia and Muscle Compensation[edit] The lingual frenulum under the tongue is part of the body's larger fascia network.[13] When the tongue is restricted by an overly tight frenulum, the tightness can travel to other nearby parts of the body such as the neck causing muscle tightness and poor posture. The tongue being restricted can force other muscles in the neck and jaw to compensate causing muscle soreness.[14][15] ## Diagnosis[edit] Ankyloglossia According to Horton et al.,[2] diagnosis of ankyloglossia may be difficult; it is not always apparent by looking at the underside of the tongue, but is often dependent on the range of movement permitted by the genioglossus muscles. For infants, passively elevating the tongue tip with a tongue depressor may reveal the problem. For older children, making the tongue move to its maximum range will demonstrate the tongue tip restriction. In addition, palpation of genioglossus on the underside of the tongue will aid in confirming the diagnosis. A severity scale for ankyloglossia, which grades the appearance and function of the tongue, is recommended for use in the Academy of Breastfeeding Medicine.[16][17] ## Treatment[edit] There are varying types of intervention for ankyloglossia. Horton et al.,[2] have a classical belief that people with ankyloglossia can compensate in their speech for a limited tongue range of motion. For example, if the tip of the tongue is restricted for making sounds such as /n, t, d, l/, the tongue can compensate through dentalization; this is when the tongue tip moves forward and up. When producing /r/, the elevation of the mandible can compensate for restriction of tongue movement. Also, compensations can be made for /s/ and /z/ by using the dorsum of the tongue for contact against the palatal rugae. Thus, Horton et al.[2] proposed compensatory strategies as a way to counteract the adverse effects of ankyloglossia and did not promote surgery. Non-surgical treatments for ankyloglossia are typically performed by Orofacial Myology specialists, and involve using exercises to strengthen and improve the function of the facial muscles and thus promote the proper function of the face, mouth, and tongue [18] Intervention for ankyloglossia does sometimes include surgery in the form of frenotomy (also called a frenectomy or frenulectomy) or frenuloplasty. This relatively common dental procedure may be done with soft-tissue lasers, such as the CO2 laser.[19] However, authors such as Horton et al. [2] are in opposition to it. According to Lalakea and Messner, surgery can be considered for patients of any age with a tight frenulum, as well as a history of speech, feeding, or mechanical/social difficulties. Adults with ankyloglossia may elect the procedure. Some of those who have done so report post-operative pain. A viable alternative to surgery for children with ankyloglossia is to take a wait-and-see approach.[9] Ruffoli et al. report that the frenulum naturally recedes during the process of a child's growth between six months and six years of age.[20][21] ## References[edit] 1. ^ Messner AH, Lalakea ML (2002). "The effect of ankyloglossia on speech in children". Otolaryngology–Head and Neck Surgery. 127 (6): 539–45. doi:10.1067/mhn.2002.1298231. PMID 12501105. 2. ^ a b c d e f g h i Horton CE, Crawford HH, Adamson JE, Ashbell TS (1969). "Tongue-tie". The Cleft Palate Journal. 6: 8–23. PMID 5251442. 3. ^ Travis, Lee Edward (1971). Handbook of speech language pathology and audiology. New York, New York: Appleton-Century-Crofts Education Division Meredith Corporation. 4. ^ a b c d Lalakea, M. Lauren; Messner, Anna H. (2003). "Ankyloglossia: The adolescent and adult perspective". Otolaryngology–Head and Neck Surgery. 128 (5): 746–52. doi:10.1016/s0194-5998(03)00258-4. PMID 12748571. 5. ^ Messner AH, Lalakea ML (2000). "Ankyloglossia: controversies in management". Int. J. Pediatr. Otorhinolaryngol. 54 (2–3): 123–31. doi:10.1016/S0165-5876(00)00359-1. PMID 10967382. 6. ^ Messner, Anna H.; Lalakea, M. Lauren; Aby, Janelle; Macmahon, James; Bair, Ellen (2000). "Ankyloglossia: Incidence and associated feeding difficulties". Archives of Otolaryngology–Head & Neck Surgery. 126 (1): 36–9. doi:10.1001/archotol.126.1.36. PMID 10628708. 7. ^ Lalakea, M. Lauren; Messner, Anna H. (2002). "Frenotomy and frenuloplasty: If, when, and how". Operative Techniques in Otolaryngology–Head and Neck Surgery. 13: 93–97. doi:10.1053/otot.2002.32157. 8. ^ Wallace, Helen; Clarke, Susan (2006). "Tongue tie division in infants with breast feeding difficulties". International Journal of Pediatric Otorhinolaryngology. 70 (7): 1257–61. doi:10.1016/j.ijporl.2006.01.004. PMID 16527363. 9. ^ a b Lalakea ML, Messner AH (2003). "Ankyloglossia: does it matter?". Pediatr. Clin. North Am. 50 (2): 381–97. doi:10.1016/S0031-3955(03)00029-4. PMID 12809329. 10. ^ a b Baxter, Richard. Tongue-tied : how a tiny string under the tongue impacts nursing, feeding, speech, and more. Musso, Megan,, Hughes, Lauren,, Lahey, Lisa,, Fabbie, Paula,, Lovvorn, Marty,, Emanuel, Michelle. Pelham, AL. ISBN 1732508208. OCLC 1046077014. 11. ^ a b Hang, William M.; Gelb, Michael (March 2017). "Airway Centric® TMJ philosophy/Airway Centric® orthodontics ushers in the post-retraction world of orthodontics". Cranio: The Journal of Craniomandibular Practice. 35 (2): 68–78. doi:10.1080/08869634.2016.1192315. ISSN 2151-0903. PMID 27356671. 12. ^ Yoon, Audrey; Zaghi, Soroush; Weitzman, Rachel; Ha, Sandy; Law, Clarice S.; Guilleminault, Christian; Liu, Stanley Y. C. (September 2017). "Toward a functional definition of ankyloglossia: validating current grading scales for lingual frenulum length and tongue mobility in 1052 subjects". Sleep & Breathing = Schlaf & Atmung. 21 (3): 767–775. doi:10.1007/s11325-016-1452-7. ISSN 1522-1709. PMID 28097623. 13. ^ Mills, Nikki; Pransky, Seth M.; Geddes, Donna T.; Mirjalili, Seyed Ali (2019). "What is a tongue tie? Defining the anatomy of the in-situ lingual frenulum". Clinical Anatomy. 32 (6): 749–761. doi:10.1002/ca.23343. ISSN 1098-2353. PMC 6850428. PMID 30701608. 14. ^ Lin, Steven (2017-08-15). "Adult Tongue-Tie Surgery Changed My Life". Dr Steven Lin. Retrieved 2019-10-29. 15. ^ Gutkowski, Shirley; Lind, Timbrey (2016). "Evaluation of a tongue-tie: The range of motion of the tongue should be assessed in all patients". www.rdhmag.com. RDH Magazine. Retrieved 2019-10-29. 16. ^ Hazelbaker AK: The assessment tool for lingual frenulum function (ATLFF): Use in a lactation consultant private practice Masters thesis, Pacific Oaks College, 1993 17. ^ ABM Protocols: Protocol #11: Guidelines for the evaluation and management of neonatal ankyloglossia and its complications in the breastfeeding dyad 18. ^ "The Ins and Outs of Tongue-Tie". OM Health. Archived from the original on 2014-11-07. Retrieved 2014-06-23. 19. ^ "Laser Surgery - Soft Tissue Dentistry". LightScalpel. 20. ^ Harris EF, Friend GW, Tolley EA (1992). "Enhanced prevalence of ankyloglossia with maternal cocaine use". Cleft Palate Craniofac. J. 29 (1): 72–6. doi:10.1597/1545-1569(1992)029<0072:EPOAWM>2.3.CO;2. PMID 1547252. 21. ^ Ruffoli R, Giambelluca MA, Scavuzzo MC, et al. (2005). "Ankyloglossia: a morphofunctional investigation in children". Oral Diseases. 11 (3): 170–4. doi:10.1111/j.1601-0825.2005.01108.x. PMID 15888108. ## External links[edit] Classification D * ICD-10: Q38.1 * ICD-9-CM: 750.0 * OMIM: 106280 * MeSH: C562396 * DiseasesDB: 33478 External resources * MedlinePlus: 001640 * 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 * t * e Congenital malformations and deformations of digestive system Upper GI tract Tongue, mouth and pharynx * Cleft lip and palate * Van der Woude syndrome * tongue * Ankyloglossia * Macroglossia * Hypoglossia Esophagus * EA/TEF * Esophageal atresia: types A, B, C, and D * Tracheoesophageal fistula: types B, C, D and E * esophageal rings * Esophageal web (upper) * Schatzki ring (lower) Stomach * Pyloric stenosis * Hiatus hernia Lower GI tract Intestines * Intestinal atresia * Duodenal atresia * Meckel's diverticulum * Hirschsprung's disease * Intestinal malrotation * Dolichocolon * Enteric duplication cyst Rectum/anal canal * Imperforate anus * Rectovestibular fistula * Persistent cloaca * Rectal atresia Accessory Pancreas * Annular pancreas * Accessory pancreas * Johanson–Blizzard syndrome * Pancreas divisum Bile duct * Choledochal cysts * Caroli disease * Biliary atresia Liver * Alagille syndrome * Polycystic liver disease [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Ankyloglossia	c0152415	27,095	wikipedia	https://en.wikipedia.org/wiki/Ankyloglossia	2021-01-18T18:55:27	{"mesh": ["D000072676"], "umls": ["C0152415"], "icd-9": ["750.0"], "wikidata": ["Q557552"]}
Plasmoacanthoma Plasmoacanthoma is a condition of the oral mucosa characterized by a verrucous tumor with a plasma cell infiltrate.[1]:797 ## See also[edit] * Plasma cell cheilitis * Skin lesion ## References[edit] 1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: Clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. * v * t * e Oral and maxillofacial pathology Lips * Cheilitis * Actinic * Angular * Plasma cell * Cleft lip * Congenital lip pit * Eclabium * Herpes labialis * Macrocheilia * Microcheilia * Nasolabial cyst * Sun poisoning * Trumpeter's wart Tongue * Ankyloglossia * Black hairy tongue * Caviar tongue * Crenated tongue * Cunnilingus tongue * Fissured tongue * Foliate papillitis * Glossitis * Geographic tongue * Median rhomboid glossitis * Transient lingual papillitis * Glossoptosis * Hypoglossia * Lingual thyroid * Macroglossia * Microglossia * Rhabdomyoma Palate * Bednar's aphthae * Cleft palate * High-arched palate * Palatal cysts of the newborn * Inflammatory papillary hyperplasia * Stomatitis nicotina * Torus palatinus Oral mucosa – Lining of mouth * Amalgam tattoo * Angina bullosa haemorrhagica * Behçet's disease * Bohn's nodules * Burning mouth syndrome * Candidiasis * Condyloma acuminatum * Darier's disease * Epulis fissuratum * Erythema multiforme * Erythroplakia * Fibroma * Giant-cell * Focal epithelial hyperplasia * Fordyce spots * Hairy leukoplakia * Hand, foot and mouth disease * Hereditary benign intraepithelial dyskeratosis * Herpangina * Herpes zoster * Intraoral dental sinus * Leukoedema * Leukoplakia * Lichen planus * Linea alba * Lupus erythematosus * Melanocytic nevus * Melanocytic oral lesion * Molluscum contagiosum * Morsicatio buccarum * Oral cancer * Benign: Squamous cell papilloma * Keratoacanthoma * Malignant: Adenosquamous carcinoma * Basaloid squamous carcinoma * Mucosal melanoma * Spindle cell carcinoma * Squamous cell carcinoma * Verrucous carcinoma * Oral florid papillomatosis * Oral melanosis * Smoker's melanosis * Pemphigoid * Benign mucous membrane * Pemphigus * Plasmoacanthoma * Stomatitis * Aphthous * Denture-related * Herpetic * Smokeless tobacco keratosis * Submucous fibrosis * Ulceration * Riga–Fede disease * Verruca vulgaris * Verruciform xanthoma * White sponge nevus Teeth (pulp, dentin, enamel) * Amelogenesis imperfecta * Ankylosis * Anodontia * Caries * Early childhood caries * Concrescence * Failure of eruption of teeth * Dens evaginatus * Talon cusp * Dentin dysplasia * Dentin hypersensitivity * Dentinogenesis imperfecta * Dilaceration * Discoloration * Ectopic enamel * Enamel hypocalcification * Enamel hypoplasia * Turner's hypoplasia * Enamel pearl * Fluorosis * Fusion * Gemination * Hyperdontia * Hypodontia * Maxillary lateral incisor agenesis * Impaction * Wisdom tooth impaction * Macrodontia * Meth mouth * Microdontia * Odontogenic tumors * Keratocystic odontogenic tumour * Odontoma * Dens in dente * Open contact * Premature eruption * Neonatal teeth * Pulp calcification * Pulp stone * Pulp canal obliteration * Pulp necrosis * Pulp polyp * Pulpitis * Regional odontodysplasia * Resorption * Shovel-shaped incisors * Supernumerary root * Taurodontism * Trauma * Avulsion * Cracked tooth syndrome * Vertical root fracture * Occlusal * Tooth loss * Edentulism * Tooth wear * Abrasion * Abfraction * Acid erosion * Attrition Periodontium (gingiva, periodontal ligament, cementum, alveolus) – Gums and tooth-supporting structures * Cementicle * Cementoblastoma * Gigantiform * Cementoma * Eruption cyst * Epulis * Pyogenic granuloma * Congenital epulis * Gingival enlargement * Gingival cyst of the adult * Gingival cyst of the newborn * Gingivitis * Desquamative * Granulomatous * Plasma cell * Hereditary gingival fibromatosis * Hypercementosis * Hypocementosis * Linear gingival erythema * Necrotizing periodontal diseases * Acute necrotizing ulcerative gingivitis * Pericoronitis * Peri-implantitis * Periodontal abscess * Periodontal trauma * Periodontitis * Aggressive * As a manifestation of systemic disease * Chronic * Perio-endo lesion * Teething Periapical, mandibular and maxillary hard tissues – Bones of jaws * Agnathia * Alveolar osteitis * Buccal exostosis * Cherubism * Idiopathic osteosclerosis * Mandibular fracture * Microgenia * Micrognathia * Intraosseous cysts * Odontogenic: periapical * Dentigerous * Buccal bifurcation * Lateral periodontal * Globulomaxillary * Calcifying odontogenic * Glandular odontogenic * Non-odontogenic: Nasopalatine duct * Median mandibular * Median palatal * Traumatic bone * Osteoma * Osteomyelitis * Osteonecrosis * Bisphosphonate-associated * Neuralgia-inducing cavitational osteonecrosis * Osteoradionecrosis * Osteoporotic bone marrow defect * Paget's disease of bone * Periapical abscess * Phoenix abscess * Periapical periodontitis * Stafne defect * Torus mandibularis Temporomandibular joints, muscles of mastication and malocclusions – Jaw joints, chewing muscles and bite abnormalities * Bruxism * Condylar resorption * Mandibular dislocation * Malocclusion * Crossbite * Open bite * Overbite * Overeruption * Overjet * Prognathia * Retrognathia * Scissor bite * Maxillary hypoplasia * Temporomandibular joint dysfunction Salivary glands * Benign lymphoepithelial lesion * Ectopic salivary gland tissue * Frey's syndrome * HIV salivary gland disease * Necrotizing sialometaplasia * Mucocele * Ranula * Pneumoparotitis * Salivary duct stricture * Salivary gland aplasia * Salivary gland atresia * Salivary gland diverticulum * Salivary gland fistula * Salivary gland hyperplasia * Salivary gland hypoplasia * Salivary gland neoplasms * Benign: Basal cell adenoma * Canalicular adenoma * Ductal papilloma * Monomorphic adenoma * Myoepithelioma * Oncocytoma * Papillary cystadenoma lymphomatosum * Pleomorphic adenoma * Sebaceous adenoma * Malignant: Acinic cell carcinoma * Adenocarcinoma * Adenoid cystic carcinoma * Carcinoma ex pleomorphic adenoma * Lymphoma * Mucoepidermoid carcinoma * Sclerosing polycystic adenosis * Sialadenitis * Parotitis * Chronic sclerosing sialadenitis * Sialectasis * Sialocele * Sialodochitis * Sialosis * Sialolithiasis * Sjögren's syndrome Orofacial soft tissues – Soft tissues around the mouth * Actinomycosis * Angioedema * Basal cell carcinoma * Cutaneous sinus of dental origin * Cystic hygroma * Gnathophyma * Ludwig's angina * Macrostomia * Melkersson–Rosenthal syndrome * Microstomia * Noma * Oral Crohn's disease * Orofacial granulomatosis * Perioral dermatitis * Pyostomatitis vegetans Other * Eagle syndrome * Hemifacial hypertrophy * Facial hemiatrophy * Oral manifestations of systemic disease This cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Plasmoacanthoma	None	27,096	wikipedia	https://en.wikipedia.org/wiki/Plasmoacanthoma	2021-01-18T19:06:57	{"wikidata": ["Q7201818"]}
A number sign (#) is used with this entry because of evidence that ventricular septal defect-1 (VSD1) is caused by heterozygous mutation in the GATA4 gene (600576) on chromosome 8p23. Description Ventricular septal defect (VSD) is the most common form of congenital cardiovascular anomaly, occurring in nearly 50% of all infants with a congenital heart defect and accounting for 14 to 16% of cardiac defects that require invasive treatment within the first year of life. Congenital VSDs may occur alone or in combination with other cardiac malformations. Large VSDs that go unrepaired may give rise to cardiac enlargement, congestive heart failure, pulmonary hypertension, Eisenmenger's syndrome, delayed fetal brain development, arrhythmias, and even sudden cardiac death (summary by Wang et al. (2011, 2011)). Other congenital cardiac defects caused by mutation in the GATA4 gene include atrial septal defect (ASD2; 607941), tetralogy of Fallot (see TOF, 187500), and endocardial cushion defects (AVSD4; 614430). ### Genetic Heterogeneity of Ventricular Septal Defect VSD2 (614431) is caused by mutation in the CITED2 gene (602937) on chromosome 6q24; VSD3 (614432) is caused by mutation in the NKX2-5 gene (600584) on chromosome 5q34. Somatic mutations in the HAND1 gene (602406) have been identified in tissue samples from patients with VSD. Molecular Genetics Zhang et al. (2008) analyzed the GATA4 gene (600576) in 486 Chinese patients with nonsyndromic congenital heart defects and identified 9 heterozygous mutations in 12 patients, including 9 (2.8%) of 319 patients with VSD (see, e.g., 600576.0007 and 600576.0009-600576.0010). Peng et al. (2010) screened 135 Chinese pediatric patients with nonfamilial congenital heart defects for mutations in GATA4 and identified a heterozygous missense mutation in 1 of 82 patients with VSD (600576.0013). Wang et al. (2011) scanned the GATA4 gene in 210 unrelated Chinese patients with VSD, 45 of whom had additional cardiac anomalies, and identified a missense mutation (600576.0014) in 1 proband (estimated population prevalence of GATA4 mutations, 0.48%). The proband was a 5-year-old girl, whose affected father and paternal aunt also carried the mutation; none of the 3 had atrioventricular conduction defects. Her father had atrial septal defect (ASD) in addition to VSD, and her deceased paternal grandfather had ASD, pulmonary stenosis, and atrioventricular block. Yang et al. (2012) identified a heterozygous missense mutation in GATA4 (R43W; 600576.0015) in 1 (0.63%) of 160 unrelated Han Chinese individuals with VSD. The proband was a 1-year-old girl from a 4-generation family in which 6 additional affected members over 3 generations were found to be heterozygous for the mutation. All affected individuals had perimembranous VSD; additional cardiac structural defects were present in 3 of the mutation-positive patients, including ASD in the proband's father and paternal grandfather and patent ductus arteriosus in her paternal aunt. A deceased paternal great uncle had VSD, ASD, and pulmonary artery stenosis. ### Associations Pending Confirmation Cheng et al. (2011) analyzed the coding region of the IRX4 gene (606199) in 698 Chinese individuals with nonsyndromic congenital cardiac malformations and identified 2 potentially disease-causing missense mutations in 2 patients with VSD who were not found in 250 controls. Both mutations were located in highly conserved regions of IRX4, and transfection studies demonstrated weakened protein-protein interactions compared to wildtype. Cheng et al. (2011) suggested that protein alterations of IRX4 may have an impact on the development of the interventricular septum. For discussion of a possible relationship between variation in the NTRK3 gene and ventricular septal defect, see 191316. INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Ventricular septal defect \- Atrial septal defect (in some patients) \- Atrioventricular conduction defect (in some patients) Vascular \- Pulmonary stenosis (in some patients) MOLECULAR BASIS \- Caused by mutation in the GATA-binding protein-4 gene (GATA4, 600576.0007 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	VENTRICULAR SEPTAL DEFECT 1	c3280777	27,097	omim	https://www.omim.org/entry/614429	2019-09-22T15:55:20	{"omim": ["614429"]}
Subcorneal pustular dermatosis (SPD) is a rare skin disease in which pus-filled pimples or blisters (pustules) form under the top (subcorneal) layer of the skin. It is most common in middle-aged adults (particularly women) but can develop in children. Pustules usually appear over a few hours and grow together to form round or wavy patterns. They most often form in areas where the skin may touch or rub together, such as the groin area, underarms, inside the elbows, and behind the knees. The pustules may be mildly itchy or painful, but despite being pus filled, are not infected. The diagnosis of SPD is made based on the appearance of the pustules and the results of a skin biopsy (histologic findings). The cause of SPD is not known. There is currently no evidence it is inherited (no familial cases have been reported) and it is not contagious. SPD may be associated with other diseases or health problems including several autoimmune diseases, blood (hematologic) diseases, infections, and cancers. Rarely, it has been associated with taking certain medications (drug-induced SPD). SPD may be treated with is oral dapsone, which often improves symptoms within one month. However, the pustules may return when treatment is stopped. Other therapies have been tried with mixed results. While SPD may cause discomfort and cosmetic concerns, it typically does not affect overall health. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	Subcorneal pustular dermatosis	c0600336	27,098	gard	https://rarediseases.info.nih.gov/diseases/13606/subcorneal-pustular-dermatosis	2021-01-18T17:57:29	{"mesh": ["D012872"], "icd-10": ["L13.1"], "orphanet": ["48377"], "synonyms": ["Sneddon-Wilkinson disease", "Sneddon Wilkinson disease", "Pustulosis subcornealis", "Subcorneal pustular dermatitis"]}
A number sign (#) is used with this entry because of evidence that the Bain type of X-linked syndromic mental retardation (MRXSB) is caused by heterozygous mutation in the HNRNPH2 gene (300610) on chromosome Xq22. Description MRXSB is an X-linked dominant neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability with behavioral abnormalities, and dysmorphic facial features. Additional variable features include musculoskeletal abnormalities, seizures, acquired microcephaly, and feeding problems with poor overall growth. Only females are affected (summary by Bain et al., 2016). Clinical Features Bain et al. (2016) reported 6 unrelated females, ranging in age from 2 to 34 years, with a complex neurodevelopmental disorder. All had delayed psychomotor development, intellectual disability, and poor or absent speech. Three patients showed developmental regression, suggesting an underlying neurodegenerative process. Most had behavioral or psychiatric abnormalities, including autism spectrum disorder, aggression, attention deficit-hyperactivity disorder, and self-injurious behavior. Additional neurologic features included hypotonia, hypertonia, and ataxic gait. Three had seizures and 2 had acquired microcephaly. Dysmorphic facial features included almond-shaped eyes, short palpebral fissures, short philtrum, full lower lip, long columella, hypoplastic alae nasi, and micrognathia. Musculoskeletal abnormalities included short stature, scoliosis, lordosis, pectus carinatum, pes planus, and joint laxity. More variable features included feeding difficulties, gastroesophageal reflux disease, and constipation. Molecular Genetics In 5 unrelated female patients with MRXSB, Bain et al. (2016) identified 3 different de novo heterozygous missense mutations in the HNRNPH2 gene: 3 patients carried the same variant (R206W; 300610.0001), 1 carried a different mutation at the same residue (R206Q; 300610.0002), and 1 carried a mutation that was 3 amino acids away (P209L; 300610.0003). All mutations affected conserved residues in the nuclear localization sequence. The patients were from a large cohort of 2,030 females and 2,486 males with developmental delay and/or intellectual disability who underwent whole-exome sequencing. Bain et al. (2016) noted that a sixth female patient with the R206W mutation and a similar phenotype was identified by another laboratory. Functional studies of the variants and studies of patient cells were not performed; however, Bain et al. (2016) noted that all mutations affected highly conserved residues in the nuclear localization sequence, and postulated a toxic gain-of-function effect. The authors suggested that these variants may be lethal in males. INHERITANCE \- X-linked dominant GROWTH Height \- Short stature Other \- Failure to thrive HEAD & NECK Head \- Microcephaly, acquired (in some patients) Face \- Short philtrum \- Micrognathia Eyes \- Hypotelorism \- Hypertelorism \- Epicanthal folds \- Short palpebral fissures \- Almond-shaped eyes Nose \- Long columella \- Hypoplastic nasal alae Mouth \- Wide mouth \- Full lips \- High-arched palate CHEST External Features \- Pectus carinatum ABDOMEN Gastrointestinal \- Feeding difficulties \- Gastroesophageal reflux disease \- Constipation SKELETAL \- Joint laxity Spine \- Scoliosis \- Lordosis Hands \- Elongated fingers Feet \- Pes planus MUSCLE, SOFT TISSUES \- Hypotonia \- Hypertonia NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Intellectual disability \- Developmental regression \- Poor or absent speech \- Hypotonia \- Hypertonia \- Gait difficulties \- Ataxia \- Seizures \- Cerebellar abnormalities (in some patients) Behavioral Psychiatric Manifestations \- Autism spectrum disorder \- Aggression \- Obsessive-compulsive disorder \- Attention deficit-hyperactivity \- Anxiety MISCELLANEOUS \- Six unrelated females have been reported (last curated October 2016) \- Variable features MOLECULAR BASIS \- Caused by mutation in the heterogeneous nuclear ribonucleoprotein H2 gene (HNRNPH2, 300610.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-aminobutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol *[5-HTP]: 5-hydroxytryptophan	MENTAL RETARDATION, X-LINKED, SYNDROMIC, BAIN TYPE	c4310814	27,099	omim	https://www.omim.org/entry/300986	2019-09-22T16:19:02	{"omim": ["300986"]}

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