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Isolated ectopia lentis (IEL) is a rare, clinically variable, eye disorder characterized by dislocation of the lens, often causing significant reduction in visual acuity. ## Epidemiology The prevalence of IEL is not known. About 90 cases have been reported to date, primarily in Europeans. ## Clinical description Patients with IEL are found to have dislocation of the lens, which may present at any age, but may be present from birth. Dislocation of the lens can be very mild leading to late diagnosis. In more severe cases, the anomaly is generally detected earlier with a greater impact on visual acuity. Lens dislocation may be progressive. Some patients are also found to have displacement of the pupils, usually in the opposite direction to lens displacement (known as ectopia lentis et pupillae). Other findings include congenital abnormalities of the iris, spherophakia, enlarged iris processes leading to abnormal iridocorneal angle, iridodonesis, lens coloboma, refractive errors (hyperopia, myopia, astigmatism), and early-onset cataract. They may develop amblyopia. Increased intraocular pressure (20%-25% of cases), retinal detachment and glaucoma may also befound. Ocular findings vary widely within families, and between the eyes in an affected individual. Visual acuity is variable depending on the severity of ocular anomalies and complications, ranging from light perception to 20/20 vision. IEL does not involve systemic abnormalities. ## Etiology Dislocation of the lens is the result of a loss of zonular fibers. Recessive mutations in the ADAMTSL4 (1q21.2) gene and dominant mutations in FBN1 gene (15q21.1) have been reported to cause IEL. Mutations in the former are thought to be the most important cause of this condition in Europeans. The exact function of these genes has not been clearly established. ADAMTSL4 mutations appear to manifest as a more severe, earlier onset condition than FBN1 mutations. ## Diagnostic methods Diagnosis is based on typical ocular findings through ophthalmologic examination and can be confirmed by molecular genetic testing of the causative genes. ## Differential diagnosis Patients with IEL by definition do not have associated systemic abnormalities, although cardiac and skeletal examinations should be performed to help exclude Marfan syndrome (diagnosed according to the Ghent criteria) (see this term). Ectopia lentis is also a feature of homocystinuria, sulfite oxidase deficiency, Weill-Marchesani syndrome, aniridia, and Knobloch syndrome (see these terms), as well as pseudoexfoliation. ## Antenatal diagnosis Prenatal diagnosis for pregnancies at increased risk is possible if the disease-causing mutations in the family have been identified. ## Genetic counseling ADAMTSL4-related IEL is inherited in an autosomal recessive manner. FBN1-related IEL follows an autosomal dominant pattern of inheritance. ## Management and treatment Visual acuity, refractive error, and intraocular pressure should be monitored regularly in affected patients. The primary aim of treatment in children is to prevent amblyopia through early correction of refractive errors. Surgical intervention may be considered by experienced ophthalmic surgeons. Lensectomy may be considered in patients with cataracts, in cases where the ectopic lens affects vision significantly. Treatment of the resulting aphakia may be with contact lenses. Alternatively, an intraocular lens (IOL) may be inserted in the anterior chamber, and sutured or glued into the posterior chamber or into the capsule, if it has been preserved during surgery. Complications include loss of accommodation, secondary glaucoma, and retinal detachment. A standard approach should be adopted in cases of retinal detachment. All patients found to have mutations in FBN1 should have regular cardiac examinations. ## Prognosis Visual prognosis depends on the degree of lens dislocation, the age of onset, age of treatment and complications. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Isolated ectopia lentis	c0013581	25,600	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1885	2021-01-23T18:57:37	{"gard": ["12251"], "mesh": ["D004479", "C536184"], "omim": ["129600", "225100", "225200"], "umls": ["C0013581", "C1851286", "C2746069"], "icd-10": ["Q12.1"], "synonyms": ["Ectopia lentis syndrome", "Familial ectopia lentis"]}
Mucopolysaccharidosis type 6 (MPS 6) is a lysosomal storage disease with progressive multisystem involvement, associated with a deficiency of arylsulfatase B (ASB) leading to the accumulation of dermatan sulfate. ## Epidemiology Birth prevalence is between 1 in 43,261 and 1 in 1,505,160 live births. ## Clinical description The disorder shows a wide spectrum of symptoms from slowly to rapidly progressing forms. The characteristic skeletal dysplasia includes short stature, dysostosis multiplex and degenerative joint disease. Rapidly progressing forms may have onset from birth, elevated urinary glycosaminoglycans (GAG, generally >100 microgram/mg creatinine), severe dysostosis multiplex, short stature, and death before the 2nd or 3rd decades. A more slowly progressing form has been described as having later onset, mildly elevated glycosaminoglycans (generally <100 microgram/mg creatinine), mild dysostosis multiplex, with death in the 4th or 5th decades. Other clinical findings may include cardiac valve disease, reduced pulmonary function, hepatosplenomegaly, sinusitis, otitis media, hearing loss, sleep apnea, corneal clouding, carpal tunnel disease, and inguinal or umbilical hernia. Although intellectual deficit is generally absent in MPS 6, central nervous system findings may include cervical cord compression caused by cervical spinal instability, meningeal thickening and/or bony stenosis, communicating hydrocephalus, optic nerve atrophy and blindness. ## Etiology The disorder is transmitted in an autosomal recessive manner and is caused by mutations in the ARSB gene, located in chromosome 5 (5q13-5q14). Over 130 ARSB mutations have been reported, causing absent or reduced arylsulfatase B (ASB or N-acetylgalactosamine 4-sulfatase) activity and interrupted dermatan sulfate and chondroitin sulfate degradation. ## Diagnostic methods Diagnosis generally requires evidence of clinical picture, ASB activity of less than 10% of the lower limit of normal in cultured fibroblasts or isolated leukocytes, and demonstration of a normal activity of a different sulfatase enzyme (to exclude mucosulfatidosis, see this term). The finding of elevated urinary dermatan sulfate with the absence of heparan sulfate is supportive. ## Differential diagnosis In addition to multiple sulfatase deficiency, the differential diagnosis should also include other forms of MPS (MPS 1, 2, 4A, 7), sialidosis and mucolipidosis (see these terms). ## Management and treatment Before enzyme replacement therapy (ERT) with galsulfase (Naglazyme®), clinical management was limited to supportive care and hematopoietic stem cell transplantation. Galsulfase is now widely available and is a specific therapy providing improved endurance with an acceptable safety profile. ## Prognosis Prognosis is variable depending on the age of onset, rate of disease progression, age at initiation of ERT and on the quality of the medical care provided. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Mucopolysaccharidosis type 6	c0026709	25,601	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=583	2021-01-23T18:30:37	{"gard": ["7095"], "mesh": ["D009087"], "omim": ["253200"], "umls": ["C0026709"], "icd-10": ["E76.2"], "synonyms": ["ARSB deficiency", "ASB deficiency", "Arylsulfatase B deficiency", "MPS6", "MPSVI", "Maroteaux-Lamy disease", "Mucopolysaccharidosis type VI", "N-acetylgalactosamine 4-sulfatase deficiency"]}
Myoclonic epilepsy SpecialtyNeurology Myoclonic epilepsy refers to a family of epilepsies that present with myoclonus. When myoclonic jerks are occasionally associated with abnormal brain wave activity, it can be categorized as myoclonic seizure. If the abnormal brain wave activity is persistent and results from ongoing seizures, then a diagnosis of myoclonic epilepsy may be considered. ## Contents * 1 Signs and symptoms * 2 Diagnosis * 2.1 Juvenile * 2.2 Progressive * 2.3 Related disorders * 2.4 Differential diagnosis * 3 References * 4 External links ## Signs and symptoms[edit] Myoclonus can be described as brief jerks of the body;[1] it can involve any part of the body, but it is mostly seen in limbs or facial muscles. The jerks are usually involuntary and can lead to falls. EEG is used to read brain wave activity. Spike activity produced from the brain is usually correlated with brief jerks seen on EMG or excessive muscle artifact. They usually occur without detectable loss of consciousness and may be generalized, regional or focal on the EEG tracing. Myoclonus jerks can be epileptic or not epileptic. Epileptic myoclonus is an elementary electroclinical manifestation of epilepsy involving descending neurons, whose spatial (spread) or temporal (self-sustained repetition) amplification can trigger overt epileptic activity.[1] ## Diagnosis[edit] There are two syndromes and several related disorders. ### Juvenile[edit] Juvenile myoclonic epilepsy is responsible for 7% of cases of epilepsy.[unreliable medical source?][2] Seizures usually begin around puberty and usually have a genetic basis.[2] Seizures can be stimulus-selective, with flashing lights being one of the most common triggers.[2] ### Progressive[edit] Progressive myoclonus epilepsy is a disease associated with myoclonus, epileptic seizures, and other problems with walking or speaking. These symptoms often worsen over time and can be fatal.[3] MERRF syndrome is also known as myoclonic epilepsy with ragged-red fibers. This rare inherited disorder affects muscles cells.[4] Features of MERRF, along with myoclonus epilepsy seizures, include ataxia, peripheral neuropathy, and dementia.[4] Lafora disease is also known as Lafora progressive myoclonus epilepsy, which is an autosomal recessive inherited disorder involving recurrent seizures and degradation of mental capabilities.[5] Lafora disease usually occurs in late childhood and usually leads to death around 10 years after first signs of the disease.[5] Unverricht-Lundborg disease is an autosomal recessive inherited disorder seen in individuals as young as six years.[6] It is associated with possible loss of consciousness, rigidity, ataxia, dysarthria, declination of mental functioning, and involuntary shaking.[6] Neuronal ceroid lipofuscinosis is a group of diseases that cause blindness, loss of mental abilities, and loss of movement.[7] All diseases in this group are lysosomal-storage disorders that also lead to death roughly ten years after onset of the disease.[7] ### Related disorders[edit] Lennox–Gastaut syndrome is often associated with intellectual deficits as well as a lack of response to anti-epileptic drugs.[8] It usually begins in the first years of life.[8] Reticular reflex myoclonus is a generalized form of epilepsy originating from the brain stem. Jerks associated with the disorder can affect all muscles on the body or be selective in certain areas.[3] Jerks can be triggered by voluntary movement or be stimulus-selective.[3] ### Differential diagnosis[edit] Myoclonic jerks that are not epileptic may be due to a nervous system disorder or other metabolic abnormalities that may arise in renal (e.g. hyperuraemia) and liver failure (e.g. high ammonia states). ## References[edit] 1. ^ a b Wyllie, Elaine (2006). The Treatment of Epilepsy. Lippincott, Williams and Wilkins. ISBN 0-7817-4995-6. 2. ^ a b c Juvenile Myoclonic Epilepsy: Characteristics and Treatment". Epilepsy.com. 3. ^ a b c Myoclonus Fact Sheet. National Institute of Neurological Disorders and Stroke. 4. ^ a b "Myoclonic epilepsy with ragged-red fibers". Genetics Home Reference. 5. ^ a b "Lafora progressive myoclonus epilepsy". Genetics Home Reference. 6. ^ a b "Unverricht-Lundborg disease". Genetics Home Reference. 7. ^ a b "Neuronal Ceroid-Lipofuscinoses". GeneReviews. 8. ^ a b Niedermeyer, Ernst (1992). "Epileptic Syndromes: A Remarkable Contribution of EEG to Epileptology". American Journal of EEG Technology (32): 10–12. ## External links[edit] Classification D * MeSH: D004831 * v * t * e Diseases of the nervous system, primarily CNS Inflammation Brain * Encephalitis * Viral encephalitis * Herpesviral encephalitis * Limbic encephalitis * Encephalitis lethargica * Cavernous sinus thrombosis * Brain abscess * Amoebic Brain and spinal cord * Encephalomyelitis * Acute disseminated * Meningitis * Meningoencephalitis Brain/ encephalopathy Degenerative Extrapyramidal and movement disorders * Basal ganglia disease * Parkinsonism * PD * Postencephalitic * NMS * PKAN * Tauopathy * PSP * Striatonigral degeneration * Hemiballismus * HD * OA * Dyskinesia * Dystonia * Status dystonicus * Spasmodic torticollis * Meige's * Blepharospasm * Athetosis * Chorea * Choreoathetosis * Myoclonus * Myoclonic epilepsy * Akathisia * Tremor * Essential tremor * Intention tremor * Restless legs * Stiff-person Dementia * Tauopathy * Alzheimer's * Early-onset * Primary progressive aphasia * Frontotemporal dementia/Frontotemporal lobar degeneration * Pick's * Dementia with Lewy bodies * Posterior cortical atrophy * Vascular dementia Mitochondrial disease * Leigh syndrome Demyelinating * Autoimmune * Inflammatory * Multiple sclerosis * For more detailed coverage, see Template:Demyelinating diseases of CNS Episodic/ paroxysmal Seizures and epilepsy * Focal * Generalised * Status epilepticus * For more detailed coverage, see Template:Epilepsy Headache * Migraine * Cluster * Tension * For more detailed coverage, see Template:Headache Cerebrovascular * TIA * Stroke * For more detailed coverage, see Template:Cerebrovascular diseases Other * Sleep disorders * For more detailed coverage, see Template:Sleep CSF * Intracranial hypertension * Hydrocephalus * Normal pressure hydrocephalus * Choroid plexus papilloma * Idiopathic intracranial hypertension * Cerebral edema * Intracranial hypotension Other * Brain herniation * Reye syndrome * Hepatic encephalopathy * Toxic encephalopathy * Hashimoto's encephalopathy Both/either Degenerative SA * Friedreich's ataxia * Ataxia–telangiectasia MND * UMN only: * Primary lateral sclerosis * Pseudobulbar palsy * Hereditary spastic paraplegia * LMN only: * Distal hereditary motor neuronopathies * Spinal muscular atrophies * SMA * SMAX1 * SMAX2 * DSMA1 * Congenital DSMA * Spinal muscular atrophy with lower extremity predominance (SMALED) * SMALED1 * SMALED2A * SMALED2B * SMA-PCH * SMA-PME * Progressive muscular atrophy * Progressive bulbar palsy * Fazio–Londe * Infantile progressive bulbar palsy * both: * Amyotrophic lateral sclerosis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Myoclonic epilepsy	c0014550	25,602	wikipedia	https://en.wikipedia.org/wiki/Myoclonic_epilepsy	2021-01-18T18:45:15	{"gard": ["7142"], "mesh": ["D004831"], "umls": ["C0014550"], "wikidata": ["Q11883686"]}
Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder of ectoderm development characterized by malformation of ectodermal structures such as skin, hair, teeth and sweat glands. It comprises three clinically almost indistinguishable subtypes with impaired sweating as the key symptom: Christ-Siemens-Touraine (CST) syndrome (X-linked), autosomal recessive (AR), and autosomal dominant (AD) HED, as well as a fourth rare subtype with immunodeficiency as the key symptom (HED with immunodeficiency) (see these terms). ## Epidemiology HED has a prevalence of approximately 1/15,000. CST syndrome is the most frequent sub-type (80% of cases) with an incidence in males of 1/50,000 to 1/100,000 births. ## Clinical description HED is characterized by a triad of signs comprising sparse hair (atrichosis/hypotrichosis), abnormal (e.g. conical) or missing teeth (anodontia/hypodontia), and decreased or absent sudation due to a lack of sweat glands (anhidrosis/hypohidrosis) which leads to heat intolerance and may cause recurrent, potentially life-threatening hyperthermic episodes. The skin is thin, dry and eczematous with regional hyperkeratosis. Most of the patients suffer from ''dry eye'' problems (e.g. chronic conjunctivitis, blepharitis), nasopharyngeal dryness and asthma-like symptoms. HED is associated with typical facial features such as a protruding forehead, sparse and fine eyebrows and eyelashes, wrinkles under the eyes, characteristic periorbital hyperpigmentation, a saddle-bridged nose, and hypoplasia of the mandible. Hair pigmentation is often absent or light. Failure to thrive may be observed. The AD and AR forms affect both sexes equally. In the X-linked form, female carriers can be asymptomatic or have a milder phenotype that may include oligodontia, conical incisors, hypotrichosis and moderate hypohidrosis. ## Etiology HED is due to mutations in genes of the ectodysplasin/NF-κB pathway, necessary for the correct development of several ectodermal structures. Mutations in EDA (Xq12-q13.1), encoding the epithelial morphogen ectodysplasin-A of the tumor necrosis factor family, cause the CST syndrome. Mutations in EDAR (2q13), encoding the Ectodysplasin-A receptor, or EDARADD(1q42.3), encoding the EDAR-associated death domain (EDARADD) protein, cause both AR and AD HED. IKBKG (Xq28) mutations cause HED with immunodeficiency. WNT10A, TRAF6, NFKBIA or EDA2R mutations may be responsible for some HED cases. ## Diagnostic methods The diagnosis is often established after hyperthermic episodes or with delayed teeth eruption. Lack of sweat glands can be evidenced by a skin biopsy or non-invasively by confocal microscopy or graphite prints of feet/hands. Sweat gland function can be assessed by quantifying pilocarpine-induced sweat production. Diagnosis is confirmed by genetic testing. ## Differential diagnosis Differential diagnoses include other types of ED like odonto-onycho-dermal dysplasia and certain forms of ichthyosis (see these terms). ## Management and treatment Uncontrolled exposure to heat must be avoided. Continuous monitoring of body temperature is required for babies placed in an incubator. Older children should adopt physical cooling measures, e.g. frequent consumption of cool liquids, wetting the clothes or wearing special cooling vests/caps. Early dental treatment aims at restoring function and improving the appearance of the teeth. Orthodontic treatment often comprises bone grafting or sinus-lift procedures followed by placement of dental implants supporting dental prostheses. HED with immunodeficiency requires immune-based therapies plus aggressive management of infections or hematopoietic stem cell transplantation. ## Prognosis If the disease is not diagnosed early enough in infancy, hyperthermia may lead to brain damage and eventually death. With early diagnosis and adequate management, most patients have a normal life expectancy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Hypohidrotic ectodermal dysplasia	c0162359	25,603	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=238468	2021-01-23T18:19:32	{"gard": ["76"], "mesh": ["D053358"], "omim": ["129490", "224900", "300291", "305100", "612132", "614940", "614941"], "umls": ["C0162359", "C0406702", "C1706004"], "icd-10": ["Q82.4"], "synonyms": ["Anhidrotic ectodermal dysplasia", "HED"]}
Rare childhood cancer of the kidneys Wilms' tumor Other namesWilms's tumor Cut section showing two halves of a nephroblastoma specimen. Note the prominent septa subdividing the sectioned surface and the protrusion of tumor into the renal pelvis, resembling botryoid rhabdomyosarcoma. Pronunciation * /vɪlmz/ SpecialtyOncology, urology, nephrology Wilms' tumor, also known as nephroblastoma, is a cancer of the kidneys that typically occurs in children, rarely in adults.[1] It is named after Max Wilms, the German surgeon (1867–1918) who first described it.[2] Approximately 650 cases are diagnosed in the U.S. annually.[3] The majority of cases occur in children with no associated genetic syndromes; however, a minority of children with Wilms' tumor have a congenital abnormality.[3] It is highly responsive to treatment, with about 9/10 children being cured.[3] ## Contents * 1 Signs and symptoms * 2 Pathogenesis * 2.1 Molecular biology and related conditions * 3 Diagnosis * 3.1 Staging * 4 Treatment/prognosis * 5 Epidemiology * 6 History * 7 See also * 8 References * 9 External links ## Signs and symptoms[edit] Typical signs and symptoms of Wilms' tumor include the following: * a painless, palpable abdominal mass * loss of appetite * abdominal pain * fever * nausea and vomiting * blood in the urine (in about 20% of cases) * high blood pressure in some cases (especially if synchronous or metachronous bilateral kidney involvement) * Rarely as varicocele[4] ## Pathogenesis[edit] Micrograph showing the characteristic triphasic pattern consisting of tubules, solid sheets of small round cells, and stroma. H&E stain. High magnification micrograph showing the epithelial component (tubules). H&E stain. Wilms' tumor has many causes, which can broadly be categorized as syndromic and non-syndromic. Syndromic causes of Wilms' tumor occur as a result of alterations to genes such as the Wilms Tumor 1 (WT1) or Wilms Tumor 2 (WT2) genes, and the tumor presents with a group of other signs and symptoms.[5] Non-syndromic Wilms' tumor is not associated with other symptoms or pathologies.[5] Many, but not all, cases of Wilms' tumor develop from nephrogenic rests, which are fragments of tissue in or around the kidney that develop before birth and become cancerous after birth. In particular, cases of bilateral Wilms' tumor, as well as cases of Wilms' tumor derived from certain genetic syndromes such as Denys-Drash syndrome, are strongly associated with nephrogenic rests.[5] Most nephroblastomas are on one side of the body only and are found on both sides in less than 5% of cases, although people with Denys-Drash syndrome mostly have bilateral or multiple tumors.[6] They tend to be encapsulated and vascularized tumors that do not cross the midline of the abdomen. In cases of metastasis it is usually to the lung. A rupture of Wilms' tumor puts the patient at risk of bleeding and peritoneal dissemination of the tumor. In such cases, surgical intervention by a surgeon who is experienced in the removal of such a fragile tumor is imperative.[citation needed] Pathologically, a triphasic nephroblastoma comprises three elements: * blastema * mesenchyme (stroma) * epithelium Wilms' tumor is a malignant tumor containing metanephric blastema, stromal and epithelial derivatives. Characteristic is the presence of abortive tubules and glomeruli surrounded by a spindled cell stroma. The stroma may include striated muscle, cartilage, bone, fat tissue, and fibrous tissue. Dysfunction is caused when the tumor compresses the normal kidney parenchyma. The mesenchymal component may include cells showing rhabdomyoid differentiation or malignancy (rhabdomyosarcomatous Wilms). Wilms' tumors may be separated into two prognostic groups based on pathologic characteristics: * Favorable – Contains well developed components mentioned above * Anaplastic – Contains diffuse anaplasia (poorly developed cells) ### Molecular biology and related conditions[edit] Mutations of the WT1 gene which is located on the short arm of chromosome 11 (11p13) are observed in approximately 20% of Wilms' tumors.[7][8] At least half of the Wilms' tumors with mutations in WT1 also carry mutations in CTNNB1, the gene encoding the proto-oncogene beta-catenin.[9] This latter gene is found on short arm of chromosome 3 (3p22.1). Most cases do not have mutations in any of these genes.[10] Syndrome Name Associated Genetic Variant Risk for Wilms tumor Description of Syndrome WAGR syndrome (Wilms tumor, aniridia, genital anomalies, retardation) Gene deletion that includes both WT1 and PAX6 45–60% Characterized by Wilms tumor, aniridia (absence of iris), hemihypertrophy (one side of body larger than the other), genitourinary abnormalities, ambiguous genitalia, intellectual disability.[11] Denys-Drash syndrome (DDS) WT1 (exon 8 and 9) 74% Characterized by kidney diseases since birth leading to early-onset kidney failure, ambiguous genitalia (intersex disorders).[11] Beckwith-Wiedemann Syndrome Abnormal regulation of chromosome 11p15.5 7% Characterized by macrosmia (large birth size), macroglossia (large tongue), hemihypertrophy (one side of the body is larger), other tumors in body, omphalocele (open abdominal wall) and visceromegaly (enlargement of organs inside abdomen).[11] An association with H19 has been reported.[12] H19 is a long noncoding RNA located on the short arm of chromosome 11 (11p15.5). ## Diagnosis[edit] Play media CT scan of 11 cm Wilms' tumor of right kidney in 13-month-old. The majority of people with Wilms' tumor present with an asymptomatic abdominal mass which is noticed by a family member or healthcare professional.[13] Renal tumors can also be found during routine screening in children who have known predisposing clinical syndromes.[13] The diagnostic process includes taking a medical history, a physical exam, and a series of tests including blood, urine, and imaging tests.[14] Once Wilms’ tumor is suspected, an ultrasound scan is usually done first to confirm the presence of an intrarenal mass.[14] A computed tomography scan or MRI scan can also be used for more detailed imaging. Finally, the diagnosis of Wilms' tumor is confirmed by a tissue sample.[15] In most cases, a biopsy is not done first because there is a risk of cancer cells spreading during the procedure. Treatment in North America is nephrectomy or in Europe chemotherapy followed by nephrectomy. A definitive diagnosis is obtained by pathological examination of the nephrectomy specimen.[15] ### Staging[edit] Staging is a standard way to describe the extent of spread of Wilms' tumors[16] and to determine prognosis and treatments. Staging is based on anatomical findings and tumor cells pathology.[17][18] According to the extent of tumor tissue at the time of initial diagnosis, five stages are considered. In Stage I Wilms' tumor (43% of cases), all of the following criteria must be met: * Tumor is limited to the kidney and is completely excised. * The surface of the renal capsule is intact. * The tumor is not ruptured or biopsied (open or needle) prior to removal. * No involvement of extrarenal or renal sinus lymph-vascular spaces * No residual tumor apparent beyond the margins of excision. * Metastasis of tumor to lymph nodes not identified. In Stage II (23% of cases), 1 or more of the following criteria must be met: * Tumor extends beyond the kidney but is completely excised. * No residual tumor apparent at or beyond the margins of excision. * Any of the following conditions may also exist: * Tumor involvement of the blood vessels of the renal sinus and/or outside the renal parenchyma. * Extensive tumor involvement of renal sinus soft tissue. In Stage III (20% of cases), 1 or more of the following criteria must be met: * Inoperable primary tumor. * Lymph node metastasis. * Tumor is present at surgical margins. * Tumor spillage involving peritoneal surfaces either before or during surgery, or transected tumor thrombus. * The tumor has been biopsied prior to removal or there is local spillage of tumor during surgery, confined to the flank. Stage IV (10% of cases) Wilms' tumor is defined by the presence of hematogenous metastases (lung, liver, bone, or brain), or lymph node metastases outside the abdomenopelvic region. Stage V (5% of cases) Wilms' tumor is defined by bilateral renal involvement at the time of initial diagnosis. For patients with bilateral involvement, an attempt should be made[according to whom?] to stage each side according to the above criteria (stage I to III) on the basis of extent of disease prior to biopsy. ## Treatment/prognosis[edit] The overall 5-year survival is estimated to be approximately 90%,[19][20] but for individuals the prognosis is highly dependent on individual staging and treatment. Early removal tends to promote positive outcomes. Tumor-specific loss-of-heterozygosity (LOH) for chromosomes 1p and 16q identifies a subset of Wilms' tumor patients who have a significantly increased risk of relapse and death. LOH for these chromosomal regions can now be used as an independent prognostic factor together with disease stage to target intensity of treatment to risk of treatment failure.[21][22] Genome-wide copy number and LOH status can be assessed with virtual karyotyping of tumor cells (fresh or paraffin-embedded). Statistics may sometimes show more favorable outcomes for more aggressive stages than for less aggressive stages, which may be caused by more aggressive treatment and/or random variability in the study groups. Also, a stage V tumor is not necessarily worse than a stage IV tumor. Stage[23] Histopathology[23] 4 Year relapse-free survival (RFS) or event-free survival (EFS)[23] 4 Year overall survival (OS)[23] Treatment[23] Stage I[23] Favorable histology in children younger than 24 months or tumor weight less than 550g 85% 98% Surgery only (should be done only within the context of a clinical trial) Favorable histology in children older than 24 months or tumor weight more than 550g 94% RFS 98% Nephrectomy \+ lymph node sampling followed by regimen EE-4A Diffuse anaplastic 68% EFS 80% Nephrectomy + lymph node sampling followed by regimen EE-4A and radiotherapy Stage II[23] Favorable histology 86% RFS 98% Nephrectomy + lymph node sampling followed by regimen EE-4A Focal anaplastic 80% EFS 80% Nephrectomy + lymph node sampling followed by abdominal radiotherapy and regimen DD-4A Diffuse anaplastic 83% EFS 82% Nephrectomy + lymph node sampling followed by abdominal radiotherapy and regimen I Stage III[23] Favorable histology 87% RFS 94% Nephrectomy + lymph node sampling followed by abdominal radiotherapy and regimen DD-4A Focal anaplastic 88% RFS 100% (8 people in study) Nephrectomy + lymph node sampling followed by abdominal radiotherapy and regimen DD-4A Focal anaplastic (preoperative treatment) 71% RFS 71% Preoperative treatment with regimen DD-4A followed by nephrectomy + lymph node sampling and abdominal radiotherapy Diffuse anaplastic 46% EFS 53% Preoperative treatment with regimen I followed by nephrectomy + lymph node sampling and abdominal radiotherapy Diffuse anaplastic 65% EFS 67% Immediate nephrectomy + lymph node sampling followed by abdominal radiotherapy and regimen I Stage IV[23] Favorable histology 76% RFS 86% Nephrectomy + lymph node sampling, followed by abdominal radiotherapy, bilateral pulmonary radiotherapy, and regimen DD-4A Focal anaplastic 61% EFS 72% Nephrectomy + lymph node sampling, followed by abdominal radiotherapy, bilateral pulmonary radiotherapy, and regimen DD-4A Diffuse anaplastic 33% EFS 33% Immediate nephrectomy + lymph node sampling followed by abdominal radiotherapy, whole-lung radiotherapy, and regimen I Diffuse anaplastic (preoperative treatment) 31% EFS 44% Preoperative treatment with regimen I followed by nephrectomy + lymph node sampling followed by abdominal radiotherapy, whole-lung radiotherapy Stage V[23] Overall 61% EFS 80% Favorable histology 65% 87% Preoperative treatment with regimen DD-4A, followed by nephron sparing surgery or nephrecomy, staging of tumors, and chemotherapy and/or radiotherapy based on pathology and staging Focal anaplastic 76% 88% Preoperative treatment with regimen DD-4A, followed by nephron sparing surgery or nephrecomy, staging of tumors, and chemotherapy and/or radiotherapy based on pathology and staging Diffuse anaplastic 25% 42% Preoperative treatment with regimen DD-4A, followed by nephron sparing surgery or nephrecomy, staging of tumors, and chemotherapy and/or radiotherapy based on pathology and staging In case of relapse of Wilms' tumor, the 4-year survival rate for children with a standard-risk has been estimated to be 80%.[24] ## Epidemiology[edit] Wilms tumor is the most common malignant renal tumor in children.[25] There are a number of rare genetic syndromes that have been linked to an increased risk of developing Wilms Tumor.[26] Screening guidelines vary between countries; however health care professionals are recommending regular ultrasound screening for people with associated genetic syndromes.[26] Wilms' tumor affects approximately one person per 10,000 worldwide before the age of 15 years.[27] People of African descent may have slightly higher rates of Wilms' tumor.[27] The peak age of Wilms' tumor is 3 to 4 years and most cases occur before the age of 10 years.[28] A genetic predisposition to Wilms' tumor in individuals with aniridia has been established, due to deletions in the p13 band on chromosome 11.[29] ## History[edit] Dr. Sidney Farber, founder of Dana–Farber Cancer Institute, and his colleagues achieved the first remissions in Wilms' tumor in the 1950s. By employing the antibiotic actinomycin D in addition to surgery and radiation therapy, they boosted cure rates from 40 to 89 percent.[citation needed] The use of computed tomography scan for the diagnosis of Wilms' tumor began in early 1970s, thanks to the intuition of Dr. Mario Costici, an Italian physician. He discovered that in the direct radiograms and in the urographic images, you can identify determining elements for a differential diagnosis with the Wilms' tumor. This possibility was a premise for starting a treatment.[30] ## See also[edit] * Hemihypertrophy * National Wilms Tumor Study Group (NWTS) * Perlman syndrome * Virtual Karyotype for 1p and 16q LOH ## References[edit] 1. ^ EBSCO database verified by URAC; accessed from Mount Sinai Hospital, New York 2. ^ WhoNamedIt.com: Max Wilms 3. ^ a b c "Wilms Tumor and Other Childhood Kidney Tumors Treatment". National Cancer Institute. Retrieved 2018-11-12. 4. ^ Erginel B, Vural S, Akın M, Karadağ CA, Sever N, Yıldız A. et al (2014) Wilms' tumor: a 24-year retrospective study from a single center. Pediatr Hematol Oncol 31: 409–414 5. ^ a b c PDQ Pediatric Treatment Editorial Board (2002), "Wilms Tumor and Other Childhood Kidney Tumors Treatment (PDQ®): Health Professional Version", PDQ Cancer Information Summaries, National Cancer Institute (US), PMID 26389282, retrieved 2018-11-26 6. ^ Guaragna MS, Soardi FC, Assumpção JG, Zambaldi L, Cardinalli IA, Yunes JA, de Mello MP, Brandalise SR, Aguiar S (August 2010). "The novel WT1 gene mutation p.H377N associated to Denys-Drash syndrome". Journal of Pediatric Hematology/Oncology. 32 (6): 486–8. doi:10.1097/MPH.0b013e3181e5e20d. PMID 20562648. S2CID 205860918. 7. ^ Call KM, Glaser T, Ito CY, Buckler AJ, Pelletier J, Haber DA, Rose EA, Kral A, Yeger H, Lewis WH (February 1990). "Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus". Cell. 60 (3): 509–20. doi:10.1016/0092-8674(90)90601-A. PMID 2154335. S2CID 29092372. 8. ^ Huff V (October 1998). "Wilms tumor genetics". American Journal of Medical Genetics. 79 (4): 260–7. doi:10.1002/(SICI)1096-8628(19981002)79:4<260::AID-AJMG6>3.0.CO;2-Q. PMID 9781905. 9. ^ Maiti S, Alam R, Amos CI, Huff V (November 2000). "Frequent association of beta-catenin and WT1 mutations in Wilms tumors". Cancer Research. 60 (22): 6288–92. PMID 11103785. 10. ^ Ruteshouser EC, Robinson SM, Huff V (June 2008). "Wilms tumor genetics: mutations in WT1, WTX, and CTNNB1 account for only about one-third of tumors". Genes, Chromosomes & Cancer. 47 (6): 461–70. doi:10.1002/gcc.20553. PMC 4332772. PMID 18311776. 11. ^ a b c Dome JS, Graf N, Geller JI, Fernandez CV, Mullen EA, Spreafico F, Van den Heuvel-Eibrink M, Pritchard-Jones K (September 2015). "Advances in Wilms Tumor Treatment and Biology: Progress Through International Collaboration". Journal of Clinical Oncology. 33 (27): 2999–3007. doi:10.1200/JCO.2015.62.1888. PMC 4567702. PMID 26304882. 12. ^ Coorens THH, Treger TD, Al-Saadi R, Moore L, Tran MGB, Mitchell TJ, Tugnait S, Thevanesan C, Young MD, Oliver TRW, Oostveen M, Collord G, Tarpey PS, Cagan A, Hooks Y, Brougham M, Reynolds BC, Barone G, Anderson J, Jorgensen M, Burke GAA, Visser J, Nicholson JC, Smeulders N, Mushtaq I, Stewart GD, Campbell PJ, Wedge DC, Martincorena I, Rampling D, Hook L, Warren AY, Coleman N, Chowdhury T, Sebire N, Drost J, Saeb-Parsy K, Stratton MR, Straathof K, Pritchard-Jones K, Behjati S (2019) Embryonal precursors of Wilms tumor. Science 366(6470):1247-1251 13. ^ a b PDQ Pediatric Treatment Editorial Board (2002). Wilms Tumor and Other Childhood Kidney Tumors Treatment (PDQ®): Health Professional Version. PDQ Cancer Information Summaries. National Cancer Institute (US). PMID 26389282. Retrieved 2018-11-12. 14. ^ a b "Presentation, diagnosis, and staging of Wilms tumor". 15. ^ a b Szychot E, Apps J, Pritchard-Jones K (January 2014). "Wilms' tumor: biology, diagnosis and treatment". Translational Pediatrics. 3 (1): 12–24. doi:10.3978/j.issn.2224-4336.2014.01.09. PMC 4728859. PMID 26835318. 16. ^ "How is Wilms tumor staged?". www.cancer.org. Retrieved 2015-11-15. 17. ^ "Wilms Tumor - Childhood - Stages". Cancer.Net. Retrieved 2015-11-15. 18. ^ "Treatment by type and stage of Wilms tumor". www.cancer.org. Retrieved 2015-11-13. 19. ^ Stewénius Y, Jin Y, Øra I, de Kraker J, Bras J, Frigyesi A, Alumets J, Sandstedt B, Meeker AK, Gisselsson D (November 2007). "Defective chromosome segregation and telomere dysfunction in aggressive Wilms' tumors". Clinical Cancer Research. 13 (22 Pt 1): 6593–602. doi:10.1158/1078-0432.CCR-07-1081. PMID 18006759. 20. ^ Tournade MF, Com-Nougué C, de Kraker J, Ludwig R, Rey A, Burgers JM, Sandstedt B, Godzinski J, Carli M, Potter R, Zucker JM (January 2001). "Optimal duration of preoperative therapy in unilateral and nonmetastatic Wilms' tumor in children older than 6 months: results of the Ninth International Society of Pediatric Oncology Wilms' Tumor Trial and Study". Journal of Clinical Oncology. 19 (2): 488–500. doi:10.1200/jco.2001.19.2.488. PMID 11208843. 21. ^ Messahel B, Williams R, Ridolfi A, A'hern R, Warren W, Tinworth L, Hobson R, Al-Saadi R, Whyman G, Brundler MA, Kelsey A, Sebire N, Jones C, Vujanic G, Pritchard-Jones K (March 2009). "Allele loss at 16q defines poorer prognosis Wilms tumour irrespective of treatment approach in the UKW1-3 clinical trials: a Children's Cancer and Leukaemia Group (CCLG) Study". European Journal of Cancer. 45 (5): 819–26. doi:10.1016/j.ejca.2009.01.005. PMID 19231157. 22. ^ Grundy PE, Breslow NE, Li S, Perlman E, Beckwith JB, Ritchey ML, Shamberger RC, Haase GM, D'Angio GJ, Donaldson M, Coppes MJ, Malogolowkin M, Shearer P, Thomas PR, Macklis R, Tomlinson G, Huff V, Green DM (October 2005). "Loss of heterozygosity for chromosomes 1p and 16q is an adverse prognostic factor in favorable-histology Wilms tumor: a report from the National Wilms Tumor Study Group". Journal of Clinical Oncology. 23 (29): 7312–21. doi:10.1200/JCO.2005.01.2799. PMID 16129848. 23. ^ a b c d e f g h i j Unless otherwise specified in boxes, then reference is: Treatment of Wilms Tumor at National Cancer Institute. Last Modified: 03/29/2012 24. ^ Spreafico F, Pritchard Jones K, Malogolowkin MH, Bergeron C, Hale J, de Kraker J, Dallorso S, Acha T, de Camargo B, Dome JS, Graf N (December 2009). "Treatment of relapsed Wilms tumors: lessons learned". Expert Review of Anticancer Therapy. 9 (12): 1807–15. doi:10.1586/era.09.159. PMID 19954292. S2CID 207212698. 25. ^ Sonn G, Shortliffe LM (October 2008). "Management of Wilms tumor: current standard of care". Nature Clinical Practice. Urology. 5 (10): 551–60. doi:10.1038/ncpuro1218. PMID 18836464. S2CID 23599363. 26. ^ a b Kalish JM, Doros L, Helman LJ, Hennekam RC, Kuiper RP, Maas SM, Maher ER, Nichols KE, Plon SE, Porter CC, Rednam S, Schultz KA, States LJ, Tomlinson GE, Zelley K, Druley TE (July 2017). "Surveillance Recommendations for Children with Overgrowth Syndromes and Predisposition to Wilms Tumors and Hepatoblastoma". Clinical Cancer Research. 23 (13): e115–e122. doi:10.1158/1078-0432.CCR-17-0710. PMC 5538793. PMID 28674120. 27. ^ a b Breslow N, Olshan A, Beckwith JB, Green DM (1993). "Epidemiology of Wilms tumor". Medical and Pediatric Oncology. 21 (3): 172–81. doi:10.1002/mpo.2950210305. PMID 7680412. 28. ^ Breslow NE, Beckwith JB, Perlman EJ, Reeve AE (September 2006). "Age distributions, birth weights, nephrogenic rests, and heterogeneity in the pathogenesis of Wilms tumor". Pediatric Blood & Cancer. 47 (3): 260–7. doi:10.1002/pbc.20891. PMC 1543666. PMID 16700047. 29. ^ Pritchard-Jones K, Fleming S, Davidson D, Bickmore W, Porteous D, Gosden C, Bard J, Buckler A, Pelletier J, Housman D (July 1990). "The candidate Wilms' tumour gene is involved in genitourinary development". Nature. 346 (6280): 194–7. Bibcode:1990Natur.346..194P. doi:10.1038/346194a0. PMID 2164159. S2CID 4350729. 30. ^ Nephroblastoma in childhood: current possibilities for an early radiographic diagnosis,Italian Journal of Surgery 1969 ## External links[edit] Classification D * ICD-10: C64 * ICD-9-CM: 189.0 * ICD-O: M8960/3 * OMIM: 194070 607102 * MeSH: D009396 * DiseasesDB: 8896 * SNOMED CT: 302849000 External resources * MedlinePlus: 001575 * eMedicine: med/3093 ped/2440 * Wilms' tumor at Curlie * GeneReviews/NCBI/NIH/UW entry on Wilms' Tumor Overview * Information from National Cancer Institute * Cancer.Net Wilms' Tumor – Childhood * v * t * e Tumors of the urinary and genital systems Kidney Glandular and epithelial neoplasm * Renal cell carcinoma * Renal oncocytoma Mixed tumor * Wilms' tumor * Mesoblastic nephroma * Clear-cell sarcoma of the kidney * Angiomyolipoma * Cystic nephroma * Metanephric adenoma by location * Renal medullary carcinoma * Juxtaglomerular cell tumor * Renal medullary fibroma Ureter * Ureteral neoplasm Bladder * Transitional cell carcinoma * Squamous-cell carcinoma * Inverted papilloma Urethra * Transitional cell carcinoma * Squamous-cell carcinoma * Adenocarcinoma * Melanoma Other * Malignant fibrous histiocytoma * v * t * e Connective/soft tissue tumors and sarcomas Not otherwise specified * Soft-tissue sarcoma * Desmoplastic small-round-cell tumor Connective tissue neoplasm Fibromatous Fibroma/fibrosarcoma: * Dermatofibrosarcoma protuberans * Desmoplastic fibroma Fibroma/fibromatosis: * Aggressive infantile fibromatosis * Aponeurotic fibroma * Collagenous fibroma * Diffuse infantile fibromatosis * Familial myxovascular fibromas * Fibroma of tendon sheath * Fibromatosis colli * Infantile digital fibromatosis * Juvenile hyaline fibromatosis * Plantar fibromatosis * Pleomorphic fibroma * Oral submucous fibrosis Histiocytoma/histiocytic sarcoma: * Benign fibrous histiocytoma * Malignant fibrous histiocytoma * Atypical fibroxanthoma * Solitary fibrous tumor Myxomatous * Myxoma/myxosarcoma * Cutaneous myxoma * Superficial acral fibromyxoma * Angiomyxoma * Ossifying fibromyxoid tumour Fibroepithelial * Brenner tumour * Fibroadenoma * Phyllodes tumor Synovial-like * Synovial sarcoma * Clear-cell sarcoma Lipomatous * Lipoma/liposarcoma * Myelolipoma * Myxoid liposarcoma * PEComa * Angiomyolipoma * Chondroid lipoma * Intradermal spindle cell lipoma * Pleomorphic lipoma * Lipoblastomatosis * Spindle cell lipoma * Hibernoma Myomatous general: * Myoma/myosarcoma smooth muscle: * Leiomyoma/leiomyosarcoma skeletal muscle: * Rhabdomyoma/rhabdomyosarcoma: Embryonal rhabdomyosarcoma * Sarcoma botryoides * Alveolar rhabdomyosarcoma * Leiomyoma * Angioleiomyoma * Angiolipoleiomyoma * Genital leiomyoma * Leiomyosarcoma * Multiple cutaneous and uterine leiomyomatosis syndrome * Multiple cutaneous leiomyoma * Neural fibrolipoma * Solitary cutaneous leiomyoma * STUMP Complex mixed and stromal * Adenomyoma * Pleomorphic adenoma * Mixed Müllerian tumor * Mesoblastic nephroma * Wilms' tumor * Malignant rhabdoid tumour * Clear-cell sarcoma of the kidney * Hepatoblastoma * Pancreatoblastoma * Carcinosarcoma Mesothelial * Mesothelioma * Adenomatoid tumor [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Wilms' tumor	c0027708	25,604	wikipedia	https://en.wikipedia.org/wiki/Wilms%27_tumor	2021-01-18T19:02:43	{"gard": ["7892"], "mesh": ["D009396"], "umls": ["C0027708", "C1333015", "C1332219"], "icd-9": ["189.0"], "icd-10": ["C64"], "wikidata": ["Q756289"]}
Zellweger spectrum disorders are a group of rare disorders that create the same disease process.[1] The subdivisions of this spectrum are hyperpipecolic acidemia, Infantile Refsum disease, neonatal adrenoleukodystrophy (NALD), and Zellweger syndrome. It can also be referred to as Peroxisomal Biogenesis Disorders, Zellweger Syndrome Spectrum, NALD, Cerebrohepatorenal Syndrome, and ZSS.[2] It can affect many body organs, including the kidneys, eyes, and hearing.[3] It is named after Hans Zellweger. ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 4 Treatment * 5 Epidemiology * 6 References ## Signs and symptoms[edit] The symptoms of the disorders can vary from every patient. Most symptoms are noticeable at birth. There is often lack in growth and muscle tone as the child develops. Also the disorders involve neurological problems. This would include frequent seizures, delays in intellectual development, and the absence in basic reflexes.[citation needed] Facial abnormalities are also often common with patients. Including a small chin, upturned nostrils, and a mouth with a highly arched roof. There are also a variety of eye abnormalities that could happen. The eye abnormalities including clouding of the cataracts and retinopathy, which can lead to vision loss. Children with Zellweger Spectrum disorder can have hearing loss with onset during the first months following birth.[4] Infants with the disorder can also have abnormalities including their organs. They might have a large spleen or liver, as well as heart defects. Including holes in the heart, and high blood pressure. Due to the lack of muscle tone, infants can face respiratory problems as the disease progresses.[citation needed] ## Causes[edit] Zellweger spectrum disorders are a group of autosomal recessive genetic disorders. They are caused due to pathogenic mutations in at least 13 different PEX genes that encode peroxins.[5] It affects the peroxisomes, which are organelles in the body that are meant to breakdown items like acids and toxic compounds. Both parents will have to have the recessive gene for the child to show symptoms. If one parent has the gene and the other one does not, the child will be a carrier and will not show symptoms. Any mutation involving the genes that create or work the peroxisomes can lead to the development of any of the Zellweger Spectrum Disorders. Both genders have an equal chance to end up with these disorders.[citation needed] ## Diagnosis[edit] Definite diagnosis requires evaluation of peroxisomal functions.[5] Mutation analysis is done from fibroblast cell lines.[6] ## Treatment[edit] Treatment may involve a team of specialists. This would include neurologists, endocrinologists, and pediatricians.[citation needed] Early intervention is important when treating someone with these disorders. Special education, physical therapy, and other medical services to aid the child through treatment. There are medical trials taking place to learn more about these disorders. Most infants that are diagnosed do not live past 6 months.[citation needed] It can be diagnosed by a blood test looking for PEX genes in the body.[clarification needed][7] ## Epidemiology[edit] It occurs in 1 in 50,000 individuals.[8] ## References[edit] 1. ^ "zellweger". Zellweger UK. Retrieved 20 February 2018. 2. ^ "Zellweger Spectrum Disorders". University of Michigan. Retrieved 20 February 2018. 3. ^ "Zellweger Spectrum Disorder". National Organization of Rare Diseases. Retrieved 20 February 2018. 4. ^ "Zellweger Syndrome". Hereditary Ocular Diseases. Retrieved 20 February 2018. 5. ^ a b Berendse, Kevin; Engelen, Marc; Ferdinandusse, Sacha; Majoie, Charles B. L. M.; Waterham, Hans R.; Vaz, Frédéric M.; Koelman, Johannes H. T. M.; Barth, Peter G.; Wanders, Ronald J. A.; Poll-The, Bwee Tien (19 August 2015). "Zellweger spectrum disorders: clinical manifestations in patients surviving into adulthood". Journal of Inherited Metabolic Disease. 39 (1): 93–106. doi:10.1007/s10545-015-9880-2. PMC 4710674. PMID 26287655. 6. ^ Ebberink, Merel S.; Mooijer, Petra A.W.; Gootjes, Jeannette; Koster, Janet; Wanders, Ronald J.A.; Waterham, Hans R. (January 2011). "Genetic classification and mutational spectrum of more than 600 patients with a Zellweger syndrome spectrum disorder" (PDF). Human Mutation. 32 (1): 59–69. doi:10.1002/humu.21388. PMID 21031596. 7. ^ "Zellweger Spectrum Disorder". Johns Hopkins Medicine. Retrieved 20 February 2018. 8. ^ "Zellweger Spectrum Disorders". U.S National Library of Medicine. Retrieved 20 February 2018. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Zellweger spectrum disorders	c1832200	25,605	wikipedia	https://en.wikipedia.org/wiki/Zellweger_spectrum_disorders	2021-01-18T18:46:53	{"gard": ["11890"], "mesh": ["C536664"], "umls": ["C1832200"], "orphanet": ["79189"], "wikidata": ["Q51250082"]}
A number sign (#) is used with this entry because of evidence that Winchester syndrome (WNCHRS) is caused by homozygous mutation in the MMP14 gene (600754) on chromosome 14q11. One such family has been reported. Description Winchester syndrome presents with severe osteolysis in the hands and feet and generalized osteoporosis and bone thinning, similar to multicentric osteolysis, nodulosis, and arthropathy (MONA; 259600), but subcutaneous nodules are characteristically absent. Various additional features including coarse face, corneal opacities, gum hypertrophy, and EKG changes have been reported (summary by Zankl et al., 2007). Clinical Features In 2 daughters of first-cousin Puerto Rican parents, Winchester et al. (1969) described a new syndrome characterized by short stature, severe joint contractures, peripheral corneal opacities, coarsened facies, dissolution of carpal and tarsal bones, and generalized osteoporosis. Changes in and about joints simulated advanced rheumatoid arthritis. Urinary mucopolysaccharide excretion was normal, but cultured skin fibroblasts showed metachromasia and increased uronic acid. Fibroblasts from the parents showed intermediate levels. Brown and Kuwabara (1970) described electron microscopic findings in a corneal biopsy from 1 of the patients reported by Winchester et al. (1969). Together with reported fibroblast studies, the authors concluded that Winchester syndrome was a mucopolysaccharide storage disease. Hollister et al. (1974) studied a Mexican family with 3 affected persons in 2 sibships related as first cousins and each apparently with consanguineous parents. On the basis of electron microscopic studies, they concluded that Winchester syndrome was a nonlysosomal connective tissue disease. Irani et al. (1978) reported a male case, the offspring of first cousins. Dunger et al. (1987) reported 2 unrelated patients with Winchester syndrome. Gum and skin biopsies from 1 patient showed active phagocytosis, an active endoplasmic reticulum, and an abundance of fibrillogranular material consistent with excessive collagen turnover. Both patients had increased urinary oligosaccharide excretion. Winter (1989) provided a review of Winchester syndrome. Molecular Genetics Evans et al. (2012) sequenced the MMP2 gene (120360) in 1 of the probands reported by Winchester et al. (1969) and found no mutations. Because of the similarity of the phenotype to that of Mmp14-null mice, they sequenced the MMP14 gene and identified a homozygous missense mutation (T17R; 600754.0001). Functional studies showed that the T17R mutation resulted in decreased amount of the active form of MMP14, although mRNA levels were unchanged. History In 2 sisters originally reported by Lambert et al. (1989) as having Winchester syndrome, Rouzier et al. (2006) identified a homozygous mutation in the MMP2 gene (120360.0004), and in an Italian patient diagnosed with Winchester syndrome, Zankl et al. (2005) identified a different homozygous mutation in the MMP2 gene (120360.0003). Based on their finding a mutation in the MMP14 gene in one of the original patients reported by Winchester et al. (1969), Evans et al. (2012) stated that the patients reported by Rouzier et al. (2006) and Zankl et al. (2005) had been misdiagnosed and actually had MONA (259600). When Winchester syndrome was thought to be allelic to MONA and Torg osteolysis, Zankl et al. (2007) had suggested that they be viewed as a continuous clinical spectrum. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	WINCHESTER SYNDROME	c0432289	25,606	omim	https://www.omim.org/entry/277950	2019-09-22T16:21:10	{"mesh": ["C536709"], "omim": ["277950"], "orphanet": ["371428"], "synonyms": ["MONA spectrum"]}
A number sign (#) is used with this entry because Leber congenital amaurosis-11 (LCA11) is caused by heterozygous mutation in the IMPDH1 gene (146690) on chromosome 7q32. Heterozygous mutation in the IMPDH1 gene can also cause retinitis pigmentosa-10 (RP10; 180105). Description Leber congenital amaurosis comprises a group of early-onset childhood retinal dystrophies characterized by vision loss, nystagmus, and severe retinal dysfunction. Patients usually present at birth with profound vision loss and pendular nystagmus. Electroretinogram (ERG) responses are usually nonrecordable. Other clinical findings may include high hypermetropia, photodysphoria, oculodigital sign, keratoconus, cataracts, and a variable appearance to the fundus (summary by Chung and Traboulsi, 2009). For a general description and a discussion of genetic heterogeneity of LCA, see 204000. Clinical Features Bowne et al. (2006) described 2 unrelated patients with Leber congenital amaurosis. The affected child in 1 family was first seen at 8 months of age when he was diagnosed with LCA and developmental delay with severe hypotonia. He had roving nystagmus with no fixation to light. Macular reflex was present in both eyes with the retina showing diffuse RPE mottling. No pigmentary deposits were present. The affected child in the other family was seen after referral at age 33 months. The parents had noted that the child could not see things in her peripheral vision and could not find her food in dimly lighted conditions. Refractive error was OD +3.50+1.50 x 85, and OS +3.50+1.50 x 95. By Allen cards, her vision was 20/40. Molecular Genetics In 2 unrelated patients with Leber congenital amaurosis-11, Bowne et al. (2006) identified heterozygous missense mutations in the IMPDH1 gene (146690.0004 and 146690.0005). INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Nystagmus \- Reduced visual acuity \- Reduced peripheral vision \- Reduced night vision \- Diffuse mottling of retinal pigment epithelium MISCELLANEOUS \- Based on report of 2 unrelated patients (last curated January 2019) \- Onset within the first few years of life MOLECULAR BASIS \- Caused by mutation in the IMP dehydrogenase-1 gene (IMPDH1, 146690.0004 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	LEBER CONGENITAL AMAUROSIS 11	c0339527	25,607	omim	https://www.omim.org/entry/613837	2019-09-22T15:57:16	{"doid": ["0110216"], "mesh": ["D057130"], "omim": ["613837"], "orphanet": ["65"], "genereviews": ["NBK531510"]}
A number sign (#) is used with this entry because oculocutaneous albinism type IV (OCA4) is caused by homozygous or compound heterozygous mutation in the MATP gene (SLC45A2; 606202) on chromosome 5p13. For a general phenotypic description and a discussion of genetic heterogeneity of oculocutaneous albinism, see OCA1 (203100). Clinical Features Newton et al. (2001) reported a Turkish patient with generalized hypopigmentation and ocular abnormalities consistent with OCA. He had white hair, pale skin, and translucent blue-gray irides. The phenotype was reminiscent of the relatively mild OCA2 (203200). Inagaki et al. (2004) reported Japanese patients with OCA4. Hair color ranged from white to yellow to brown, and iris color ranged from blue to brown. Most patients had nystagmus. Rundshagen et al. (2004) reported 5 unrelated German patients with OCA4. Clinical features included lack of pigmentation of the skin, hair, and eyes associated with classic albinism ocular abnormalities, including decreased visual acuity, macular hypoplasia, optic dysplasia, atypical choroidal vessels, and nystagmus. Most patients did not show increased pigmentation with age or ability to tan. Molecular Genetics Newton et al. (2001) identified a homozygous mutation in the SLC45A2 gene (606202.0001) in a Turkish patient with OCA4. The patient's parents were heterozygous for the mutation. Rundshagen et al. (2004) screened 176 German patients with albinism for mutations in the MATP gene; in 5, they identified homozygous or compound heterozygous mutations (see 606202.0002-606202.0005). These 5 patients were considered to be affected by OCA4. In 18 of 75 (24%) unrelated Japanese patients with OCA, Inagaki et al. (2004) identified 7 mutations in the MATP gene (see, e.g., D157N, 606202.0006). The authors suggested that OCA4 is one of the most common types of albinism in Japan. Inagaki et al. (2005) investigated the haplotypes of 20 alleles carrying the D157N mutation from 1 Korean and 21 Japanese OCA4 patients and found 1 Korean and 12 Japanese alleles to be associated with so-called 'haplotype 15' (G-A-G-A-G). Their results were consistent with a founder effect for the D157N mutation in East Asia, suggesting that Japan and Korea might be areas with a high prevalence of OCA4. Inagaki et al. (2005) suggested that the D157N mutation might have occurred on an ancestral chromosome after the divergence of East Asians and Caucasians approximately 15,000 to 35,000 years ago. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	ALBINISM, OCULOCUTANEOUS, TYPE IV	c1847836	25,608	omim	https://www.omim.org/entry/606574	2019-09-22T16:10:19	{"doid": ["0070098"], "mesh": ["C564696"], "omim": ["606574"], "orphanet": ["79435"], "synonyms": ["Alternative titles", "OCULOCUTANEOUS ALBINISM, TYPE IV"], "genereviews": ["NBK1510"]}
Radiation burn Other namesRadiodermatitis Ionizing radiation burn: large red patches of skin on the back and arm from multiple prolonged fluoroscopy procedures SpecialtyDermatology A radiation burn is a damage to the skin or other biological tissue and organs as an effect of radiation. The radiation types of greatest concern are thermal radiation, radio frequency energy, ultraviolet light and ionizing radiation. The most common type of radiation burn is a sunburn caused by UV radiation. High exposure to X-rays during diagnostic medical imaging or radiotherapy can also result in radiation burns. As the ionizing radiation interacts with cells within the body—damaging them—the body responds to this damage, typically resulting in erythema—that is, redness around the damaged area. Radiation burns are often discussed in the same context as radiation-induced cancer due to the ability of ionizing radiation to interact with and damage DNA, occasionally inducing a cell to become cancerous. Cavity magnetrons can be improperly used to create surface and internal burning. Depending on the photon energy, gamma radiation can cause very deep gamma burns, with 60Co internal burns common. Beta burns tend to be shallow as beta particles are not able to penetrate deeply into the person; these burns can be similar to sunburn. Alpha particles can cause internal alpha burns if inhaled, with external damage (if any) being limited to minor erythema. Radiation burns can also occur with high power radio transmitters at any frequency where the body absorbs radio frequency energy and converts it to heat.[1] The U.S. Federal Communications Commission (FCC) considers 50 watts to be the lowest power above which radio stations must evaluate emission safety. Frequencies considered especially dangerous occur where the human body can become resonant, at 35 MHz, 70 MHz, 80-100 MHz, 400 MHz, and 1 GHz.[2] Exposure to microwaves of too high intensity can cause microwave burns. ## Contents * 1 Types * 1.1 Acute * 1.2 Chronic * 1.3 Other * 1.4 Delayed effects * 2 Alpha burns * 3 Beta burns * 3.1 Energy vs penetration depth * 4 Causes * 4.1 Medical imaging * 4.2 Radioactive fallout * 4.3 Nuclear accidents * 5 Treatment * 6 See also * 7 References * 8 External links ## Types[edit] Radiation dermatitis (also known as radiodermatitis) is a skin disease associated with prolonged exposure to ionizing radiation.[3]:131–2 Radiation dermatitis occurs to some degree in most patients receiving radiation therapy, with or without chemotherapy.[4] There are three specific types of radiodermatitis: acute radiodermatitis, chronic radiodermatitis, and eosinophilic, polymorphic, and pruritic eruption associated with radiotherapy.[3]:39–40 Radiation therapy can also cause radiation cancer.[3]:40 With interventional fluoroscopy, because of the high skin doses that can be generated in the course of the intervention, some procedures have resulted in early (less than two months after exposure) and/or late (two months or more after exposure) skin reactions, including necrosis in some cases.[5]:773 Radiation dermatitis, in the form of intense erythema and vesiculation of the skin, may be observed in radiation ports.[3]:131 As many as 95% of patients treated with radiation therapy for cancer will experience a skin reaction. Some reactions are immediate, while others may be later (e.g., months after treatment).[6] ### Acute[edit] Acute radiodermatitis occurs when an "erythema dose" of ionizing radiation is given to the skin, after which visible erythema appears up to 24 hours after.[3]:39 Radiation dermatitis generally manifests within a few weeks after the start of radiotherapy.[4]:143 Acute radiodermatitis, while presenting as red patches, may sometimes also present with desquamation or blistering.[7] Erythema may occur at a dose of 2 Gy radiation or greater.[8] ### Chronic[edit] Chronic radiodermatitis occurs with chronic exposure to "sub-erythema" doses of ionizing radiation over a prolonged period, producing varying degrees of damage to the skin and its underlying parts after a variable latent period of several months to several decades.[3]:40 In the distant past this type of radiation reaction occurred most frequently in radiologists and radiographers who were constantly exposed to ionizing radiation, especially before the use of X-ray filters.[3]:40 Chronic radiodermatitis, squamous and basal cell carcinomas may develop months to years after radiation exposure.[7]:130[9] Chronic radiodermatitis presents as atrophic indurated plaques, often whitish or yellowish, with telangiectasia, sometimes with hyperkeratosis.[7]:130 ### Other[edit] Eosinophilic, polymorphic, and pruritic eruption associated with radiotherapy is a skin condition that occurs most often in women receiving cobalt radiotherapy for internal cancer.[3]:39–40 Radiation-induced erythema multiforme may occur when phenytoin is given prophylactically to neurosurgical patients who are receiving whole-brain therapy and systemic steroids.[3]:130 ### Delayed effects[edit] Radiation acne is a cutaneous condition characterized by comedo-like papules occurring at sites of previous exposure to therapeutic ionizing radiation, skin lesions that begin to appear as the acute phase of radiation dermatitis begins to resolve.[10]:501 Radiation recall reactions occur months to years after radiation treatment, a reaction that follows recent administration of a chemotherapeutic agent and occurs with the prior radiation port, characterized by features of radiation dermatitis.[3][11] Restated, radiation recall dermatitis is an inflammatory skin reaction that occurs in a previously irradiated body part following drug administration.[12] There does not appear to be a minimum dose, nor an established radiotherapy dose relationship.[12] ## Alpha burns[edit] "Alpha burns" are caused by alpha particles, which can cause extensive tissue damage if inhaled.[13] Due to the keratin in the epidermal layer of the skin, external alpha burns are limited to only mild reddening of the outermost layer of skin.[14] ## Beta burns[edit] "Beta burns"—caused by beta particles—are shallow surface burns, usually of skin and less often of lungs or gastrointestinal tract, caused by beta particles, typically from hot particles or dissolved radionuclides that came to direct contact with or close proximity to the body. They can appear similar to sunburn. Unlike gamma rays, beta emissions are stopped much more effectively by materials and therefore deposit all their energy in only a shallow layer of tissue, causing more intense but more localized damage. On cellular level, the changes in skin are similar to radiodermatitis. High doses of radiation can cause rapid browning of skin, known as "nuclear tan".[citation needed] The dose is influenced by relatively low penetration of beta emissions through materials. The cornified keratine layer of epidermis has enough stopping power to absorb beta radiation with energies lower than 70 keV. Further protection is provided by clothing, especially shoes. The dose is further reduced by limited retention of radioactive particles on skin; a 1 millimeter particle is typically released in 2 hours, while a 50 micrometer particle usually does not adhere for more than 7 hours. Beta emissions are also severely attenuated by air; their range generally does not exceed 6 feet (1.8 m) and intensity rapidly diminishes with distance.[15] The eye lens seems to be the most sensitive organ to beta radiation,[16] even in doses far below maximum permissible dose. Safety goggles are recommended to attenuate strong beta.[17] Beta burns can occur also to plants. An example of such damage is the Red Forest, a victim of the Chernobyl accident. Careful washing of exposed body surface, removing the radioactive particles, may provide significant dose reduction. Exchanging or at least brushing off clothes also provides a degree of protection. If the exposure to beta radiation is intense, the beta burns may first manifest in 24–48 hours by itching and/or burning sensation that last for one or two days, sometimes accompanied by hyperaemia. After 1–3 weeks burn symptoms appear; erythema, increased skin pigmentation (dark colored patches and raised areas), followed by epilation and skin lesions. Erythema occurs after 5–15 Gy, dry desquamation after 17 Gy, and bullous epidermitis after 72 Gy.[15] Chronic radiation keratosis may develop after higher doses. Primary erythema lasting more than 72 hours is an indication of injury severe enough to cause chronic radiation dermatitis. Edema of dermal papillae, if present within 48 hours since the exposition, is followed by transepidermal necrosis. After higher doses, the malpighian layer cells die within 24 hours; lower doses may take 10–14 days to show dead cells.[18] Inhalation of beta radioactive isotopes may cause beta burns of lungs and nasopharyngeal region, ingestion may lead to burns of gastrointestinal tract; the latter being a risk especially for grazing animals. * In first degree beta burns the damage is largely limited to epidermis. Dry or wet desquamation occurs; dry scabs are formed, then heal rapidly, leaving a depigmented area surrounded with irregular area of increased pigmentation. The skin pigmentation returns to normal within several weeks. * Second degree beta burns lead to formation of blisters. * Third and fourth degree beta burns result in deeper, wet ulcerated lesions, which heal with routine medical care after covering themselves with dry scab. In case of heavy tissue damage, ulcerated necrotic dermatitis may occur. Pigmentation may return to normal within several months after wound healing.[15] Lost hair begins regrowing in nine weeks and is completely restored in about half a year.[19] The acute dose-dependent effects of beta radiation on skin are as follows:[20] 0–6 Gy no acute effect 6–20 Gy moderate early erythema 20–40 Gy early erythema in 24 hours, skin breakdown in 2 weeks 40–100 Gy severe erythema in less than 24 hours 100–150 Gy severe erythema in less than 4 hours, skin breakdown in 1–2 weeks 150–1000 Gy blistering immediate or up to 1 day According to other source:[21] 2–6 Gy transient erythema 2–24 h 3–5 Gy dry desquamation in 3–6 weeks 3–4 Gy temporary epilation in 3 weeks 10–15 Gy erythema 18–20 days 15–20 Gy moist desquamation 25 Gy ulceration with slow healing 30–50 Gy blistering, necrosis in 3 weeks 100 Gy blistering, necrosis in 1–3 weeks As shown, the dose thresholds for symptoms vary by source and even individually. In practice, determining the exact dose tends to be difficult. Similar effects apply to animals, with fur acting as additional factor for both increased particle retention and partial skin shielding. Unshorn thickly wooled sheep are well protected; while the epilation threshold for sheared sheep is between 23–47 Gy (2500–5000 rep) and the threshold for normally wooled face is 47–93 Gy (5000–10000 rep), for thickly wooled (33 mm hair length) sheep it is 93–140 Gy (10000–15000 rep). To produce skin lesions comparable with contagious pustular dermatitis, the estimated dose is between 465–1395 Gy.[22] ### Energy vs penetration depth[edit] Medium-lived fission products Prop: Unit: t½ (a) Yield (%) Q * (keV) βγ * 155Eu 4.76 0.0803 252 βγ 85Kr 10.76 0.2180 687 βγ 113mCd 14.1 0.0008 316 β 90Sr 28.9 4.505 2826 β 137Cs 30.23 6.337 1176 βγ 121mSn 43.9 0.00005 390 βγ 151Sm 88.8 0.5314 77 β The effects depend on both the intensity and the energy of the radiation. Low-energy beta (sulfur-35, 170 keV) produces shallow ulcers with little damage to dermis, while cobalt-60 (310 keV), caesium-137 (550 keV), phosphorus-32 (1.71 MeV), strontium-90 (650 keV) and its daughter product yttrium-90 (2.3 MeV) damage deeper levels of the dermis and can result in chronic radiation dermatitis. Very high energies from electron beams from particle accelerators, reaching tens of megaelectronvolts, can be deeply penetrating. Conversely, megavolt-scale beams can deposit their energy deeper with less damage to the dermis; modern radiotherapy electron beam accelerators take advantage of this. At yet higher energies, above 16 MeV, the effect does not show significantly anymore, limiting the usefulness of higher energies for radiotherapy. As a convention, surface is defined as the topmost 0.5 mm of skin.[23] High-energy beta emissions should be shielded with plastic instead of lead, as high-Z elements generate deeply penetrating gamma bremsstrahlung. The electron energies from beta decay are not discrete but form a continuous spectrum with a cutoff at maximum energy. The rest of the energy of each decay is carried off by an antineutrino which does not significantly interact and therefore does not contribute to the dose. Most energies of beta emissions are at about a third of the maximum energy.[17] Beta emissions have much lower energies than what is achievable from particle accelerators, no more than few megaelectronvolts. The energy-depth-dose profile is a curve starting with a surface dose, ascending to the maximum dose in a certain depth dm (usually normalized as 100% dose), then descends slowly through depths of 90% dose (d90) and 80% dose (d80), then falls off linearly and relatively sharply though depth of 50% dose (d50). The extrapolation of this linear part of the curve to zero defines the maximum electron range, Rp. In practice, there is a long tail of weaker but deep dose, called "bremsstrahlung tail", attributable to bremsstrahlung. The penetration depth depends also on beam shape, narrower beam tend to have less penetration. In water, broad electron beams, as is the case in homogeneous surface contamination of skin, have d80 about E/3 cm and Rp about E/2 cm, where E is the beta particle energy in MeV.[24] The penetration depth of lower-energy beta in water (and soft tissues) is about 2 mm/MeV. For a 2.3 MeV beta the maximum depth in water is 11 mm, for 1.1 MeV it is 4.6 mm. The depth where maximum of the energy is deposited is significantly lower.[25] The energy and penetration depth of several isotopes is as follows:[26] isotope half-life specific activity (TBq/g) avg. (keV) max. (keV) in air (mm) in tissue (mm) comment tritium 12.3 years 357 5.7 18.6 6 0.006 no beta passes the dead layer of skin; however, tritium and its compounds may diffuse through skin carbon-14 5730 years 0.165 49 156 240 0.28 about 1% of beta passes through the dead layer of skin sulfur-35 87.44 days 1580 48.8 167.47 260 0.32 phosphorus-33 25.3 days 5780 76.4 248.5 500 0.6 phosphorus-32 14.29 days 10600 695 1710 6100 7.6 risk of Bremsstrahlung if improperly shielded For a wide beam, the depth-energy relation for dose ranges is as follows, for energies in megaelectronvolts and depths in millimeters. The dependence of surface dose and penetration depth on beam energy is clearly visible.[24] MeV surface dose % max. depth 90% 80% 50% 10% Rp 5 74% 9 12 14 17 22 23 7 76% 16 20 22 27 33 34 10 82% 24 31 34 39 48 49 13 88% 32 40 43 51 61 64 16 93% 34 51 56 65 80 80 19 94% 26–36 59 67 78 95 95 22 96% 26–36 65 76 93 113 114 25 96% 26–36 65 80 101 124 124 ## Causes[edit] Radiation burns are caused by exposure to high levels of radiation. Levels high enough to cause burn are generally lethal if received as a whole-body dose, whereas they may be treatable if received as a shallow or local dose. ### Medical imaging[edit] Fluoroscopy may cause burns if performed repeatedly or for too long.[10] Similarly, X-ray computed tomography and traditional projectional radiography have the potential to cause radiation burns if the exposure factors and exposure time are not appropriately controlled by the operator. A study of radiation-induced skin injuries[27][28] has been performed by the Food and Drug Administration (FDA) based on results from 1994,[29] followed by an advisory to minimize further fluoroscopy-induced injuries.[30] The problem of radiation injuries due to fluoroscopy has been further investigated in review articles in 2000,[31] 2001,[32][33] 2009[34] and 2010.[35][36][37] ### Radioactive fallout[edit] Beta burns are frequently the result of exposure to radioactive fallout after nuclear explosions or nuclear accidents. Shortly after the explosion, the fission products have very high beta activity, with about two beta emissions per each gamma photon. After the Trinity test, the fallout caused localized burns on the backs of cattle in the area downwind.[38] The fallout had the appearance of small flaky dust particles. The cattle showed temporary burns, bleeding, and loss of hair. Dogs were also affected; in addition to localized burns on their backs, they also had burned paws, likely from the particles lodged between their toes as hoofed animals did not show problems with feet. About 350–600 cattle were affected by superficial burns and localized temporary loss of dorsal hair; the army later bought 75 most affected cows as the discolored regrown hair lowered their market value.[39] The cows were shipped to Los Alamos and Oak Ridge, where they were observed. They healed, now sporting large patches of white fur; some looked as if they had been scalded.[40] The fallout produced by the Castle Bravo test was unexpectedly strong. A white snow-like dust, nicknamed by the scientists "Bikini snow" and consisting of contaminated crushed calcined coral, fell for about 12 hours upon the Rongelap Atoll, depositing a layer of up to 2 cm. Residents suffered beta burns, mostly on the backs of their necks and on their feet,[38] and were resettled after three days. After 24–48 hours their skin was itching and burning; in a day or two the sensations subsided, to be followed after 2–3 weeks by epilation and ulcers. Darker-colored patches and raised areas appeared on their skin, blistering was uncommon. Ulcers formed dry scabs and healed. Deeper lesions, painful, weeping and ulcerated, formed on more contaminated residents; the majority healed with simple treatment. In general, the beta burns healed with some cutaneous scarring and depigmentation. Individuals who bathed and washed the fallout particles from their skin did not develop skin lesions.[20] The fishing ship Daigo Fukuryu Maru was affected by the fallout as well; the crew suffered skin doses between 1.7–6.0 Gy, with beta burns manifesting as severe skin lesions, erythema, erosions, sometimes necrosis, and skin atrophy. Twenty-three U.S. radar servicemen of the 28-member weather station on Rongerik[41] were affected, experiencing discrete 1–4 mm skin lesions which healed quickly, and ridging of fingernails several months later. Sixteen crew members of the aircraft carrier USS Bairoko received beta burns, and there was an increased cancer rate.[15] During the Zebra test of the Operation Sandstone in 1948, three men suffered beta burns on their hands when removing sample collection filters from drones flying through the mushroom cloud; their estimated skin surface dose was 28 to 149 Gy, and their disfigured hands required skin grafts. A fourth man showed weaker burns after the earlier Yoke test.[42] The Upshot–Knothole Harry test at the Frenchman Flat site released a large amount of fallout. A significant number of sheep died after grazing on contaminated areas. The AEC however had a policy to compensate farmers only for animals showing external beta burns, so many claims were denied. Other tests on the Nevada Test Site also caused fallout and corresponding beta burns to sheep, horses and cattle.[43] During the Operation Upshot–Knothole, sheep as far as 50 miles (80 km) from the test site suffered beta burns to their backs and nostrils.[42] During underground nuclear testing in Nevada, several workers developed burns and skin ulcers, in part attributed to exposure to tritium.[44] ### Nuclear accidents[edit] Beta burns were a serious medical issue for some victims of the Chernobyl disaster; from 115 patients treated in Moscow, 30% had burns covering 10–50% of body surface, 11% were affected on 50–100% of skin; the massive exposure was often caused by clothes drenched with radioactive water. Some firefighters suffered beta burns of lungs and nasopharyngeal region after inhalation of massive amounts of radioactive smoke. Out of 28 deaths, 16 had skin injuries listed among the causes. The beta activity was extremely high, with beta/gamma ratio reaching 10–30[clarification needed] and beta energy high enough to damage basal layer of the skin, resulting in large area portals for infections, exacerbated by damage to bone marrow and weakened immune system. Some patients received skin dose of 400–500 Gy. The infections caused more than half of the acute deaths. Several died of fourth degree beta burns between 9–28 days after dose of 6–16 Gy. Seven died after dose of 4–6 Gy and third degree beta burns in 4–6 weeks. One died later from second degree beta burns and dose 1-4 Gy.[44] The survivors have atrophied skin which is spider veined and with underlying fibrosis.[15] The burns may manifest at different times at different body areas. The Chernobyl liquidators’ burns first appeared on wrists, face, neck and feet, followed by chest and back, then by knees, hips and buttocks.[45] Industrial radiography sources are a common source of beta burns in workers. Radiation therapy sources can cause beta burns during exposure of the patients. The sources can be also lost and mishandled, as in the Goiânia accident, during which several people suffered external beta burns and more serious gamma burns, and several died. Numerous accidents also occur during radiotherapy due to equipment failures, operator errors, or wrong dosage. Electron beam sources and particle accelerators can be also sources of beta burns.[46] The burns may be fairly deep and require skin grafts, tissue resection or even amputation of fingers or limbs.[47] ## Treatment[edit] Radiation burns should be covered by a clean, dry dressing as soon as possible to prevent infection. Wet dressings are not recommended.[48] The presence of combined injury (exposure to radiation plus trauma or radiation burn) increases the likelihood of generalized sepsis.[49] This requires administration of systemic antimicrobial therapy.[50] ## See also[edit] * Effective radiated power * Radiation poisoning * Radiation protection * Therac-25 ## References[edit] 1. ^ ARRL: RF Exposure Regulations News Archived 2008-05-17 at the Wayback Machine 2. ^ ARRL: RF Radiation and Electromagnetic Field Safety 3. ^ a b c d e f g h i j James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. 4. ^ a b Bernier, J.; Bonner, J; Vermorken, J. B.; Bensadoun, R.-J.; Dummer, R.; Giralt, J.; Kornek, G.; Hartley, A.; et al. (January 2008). "Consensus guidelines for the management of radiation dermatitis and coexisting acne-like rash in patients receiving radiotherapy plus EGFR inhibitors for the treatment of squamous cell carcinoma of the head and neck" (PDF). Annals of Oncology. 19 (1): 142–9. doi:10.1093/annonc/mdm400. PMID 17785763. 5. ^ Wagner, LK; McNeese, MD; Marx, MV; Siegel, EL (December 1999). "Severe skin reactions from interventional fluoroscopy: case report and review of the literature". Radiology. 213 (3): 773–6. doi:10.1148/radiology.213.3.r99dc16773. PMID 10580952. 6. ^ Porock D, Nikoletti S, Kristjanson L (1999). "Management of radiation skin reactions: literature review and clinical application". Plast Surg Nurs. 19 (4): 185–92, 223, quiz 191–2. doi:10.1097/00006527-199901940-00004. PMID 12024597. 7. ^ a b c Rapini, Ronald P. (2005). Practical dermatopathology. Elsevier Mosby. ISBN 978-0-323-01198-3. 8. ^ Valentin J (2000). "Avoidance of radiation injuries from medical interventional procedures". Ann ICRP. 30 (2): 7–67. doi:10.1016/S0146-6453(01)00004-5. PMID 11459599. S2CID 70923586. 9. ^ Dehen L, Vilmer C, Humilière C, et al. (March 1999). "Chronic radiodermatitis following cardiac catheterisation: a report of two cases and a brief review of the literature". Heart. 81 (3): 308–12. doi:10.1136/hrt.81.3.308. PMC 1728981. PMID 10026359. 10. ^ a b Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 11. ^ Hird AE, Wilson J, Symons S, Sinclair E, Davis M, Chow E. Radiation recall dermatitis: case report and review of the literature. Current Oncology. 2008 February; 15(1):53-62. 12. ^ a b Ayoola, A.; Lee, Y. J. (2006). "Radiation recall dermatitis with cefotetan: a case study". The Oncologist. 11 (10): 1118–1120. doi:10.1634/theoncologist.11-10-1118. PMID 17110631. 13. ^ Bhattacharya, S. (2010). "Radiation injury". Indian Journal of Plastic Surgery. 43 (Suppl): S91–S93. doi:10.1055/s-0039-1699465. 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Nuclear handbook for medical service personnel. p. 18. 21. ^ Medical decision making and care of casualties from delayed effects of a nuclear detonation[permanent dead link], Fred A. Mettler Jr., New Mexico Federal Regional Medical Center 22. ^ National Research Council (U.S.). Committee on Physiological Effects of Environmental Factors on Animals (1971). A guide to environmental research on animals. National Academies. p. 224. ISBN 9780309018692. 23. ^ Philip Mayles; Alan E. Nahum; Jean-Claude Rosenwald (2007). Handbook of radiotherapy physics: theory and practice. CRC Press. p. 522. ISBN 978-0-7503-0860-1. 24. ^ a b Mike Benjamin Siroky; Robert D. Oates; Richard K. Babayan (2004). Handbook of urology: diagnosis and therapy. Lippincott Williams & Wilkins. p. 328. ISBN 978-0-7817-4221-4. 25. ^ α, β, γ Penetration and Shielding. Fas.harvard.edu. 26. ^ Isotope Safety Data Sheets 27. ^ Shope, T. B. (1995). "Radiation-induced Skin Injuries from Fluoroscopy". FDA / Center for Devices and Radiological Health. 28. ^ Shope, T. B. (1996). "Radiation-induced skin injuries from fluoroscopy". Radiographics. 16 (5): 1195–1199. doi:10.1148/radiographics.16.5.8888398. PMID 8888398. 29. ^ Wagner, L. K.; Eifel, P. J.; Geise, R. A. (1994). "Potential biological effects following high X-ray dose interventional procedures". Journal of Vascular and Interventional Radiology. 5 (1): 71–84. doi:10.1016/s1051-0443(94)71456-1. PMID 8136601. 30. ^ "FDA Public Health Advisory: Avoidance of Serious X-Ray-Induced Skin Injuries to Patients During Fluoroscopically-Guided Procedures". FDA / Center for Devices and Radiological Health. September 30, 1994. 31. ^ Valentin, J. (2000). "Avoidance of radiation injuries from medical interventional procedures". Annals of the ICRP. 30 (2): 7–67. doi:10.1016/S0146-6453(01)00004-5. PMID 11459599. S2CID 70923586. 32. ^ Vano, E.; Goicolea, J.; Galvan, C.; Gonzalez, L.; Meiggs, L.; Ten, J. I.; Macaya, C. (2001). "Skin radiation injuries in patients following repeated coronary angioplasty procedures". The British Journal of Radiology. 74 (887): 1023–1031. doi:10.1259/bjr.74.887.741023. PMID 11709468. 33. ^ Koenig, T. R.; Mettler, F. A.; Wagner, L. K. (2001). "Skin injuries from fluoroscopically guided procedures: Part 2, review of 73 cases and recommendations for minimizing dose delivered to patient". AJR. American Journal of Roentgenology. 177 (1): 13–20. doi:10.2214/ajr.177.1.1770013. PMID 11418390. 34. ^ Ukisu, R.; Kushihashi, T.; Soh, I. (2009). "Skin Injuries Caused by Fluoroscopically Guided Interventional Procedures: Case-Based Review and Self-Assessment Module". American Journal of Roentgenology. 193 (6_Supplement): S59–S69. doi:10.2214/AJR.07.7140. PMID 19933677. 35. ^ Chida, K.; Kato, M.; Kagaya, Y.; Zuguchi, M.; Saito, H.; Ishibashi, T.; Takahashi, S.; Yamada, S.; Takai, Y. (2010). "Radiation dose and radiation protection for patients and physicians during interventional procedure" (pdf). Journal of Radiation Research. 51 (2): 97–105. Bibcode:2010JRadR..51...97C. doi:10.1269/jrr.09112. PMID 20339253.[permanent dead link] 36. ^ Balter, S.; Hopewell, J. W.; Miller, D. L.; Wagner, L. K.; Zelefsky, M. J. (2010). "Fluoroscopically Guided Interventional Procedures: A Review of Radiation Effects on Patients' Skin and Hair". Radiology. 254 (2): 326–341. doi:10.1148/radiol.2542082312. PMID 20093507. 37. ^ Miller, D. L.; Balter, S.; Schueler, B. A.; Wagner, L. K.; Strauss, K. J.; Vano, E. (2010). "Clinical Radiation Management for Fluoroscopically Guided Interventional Procedures". Radiology. 257 (2): 321–332. doi:10.1148/radiol.10091269. PMID 20959547. 38. ^ a b National Research Council (U.S.). Committee on Fire Research, United States. Office of Civil Defense (1969). Mass burns: proceedings of a workshop, 13–14 March 1968. National Academies. p. 248. 39. ^ Barton C. Hacker (1987). The dragon's tail: radiation safety in the Manhattan Project, 1942–1946. University of California Press. p. 105. ISBN 978-0-520-05852-1. "beta burns." 40. ^ Ferenc Morton Szasz (1984). The day the sun rose twice: the story of the Trinity Site nuclear explosion, July 16, 1945. UNM Press. p. 134. ISBN 978-0-8263-0768-2. 41. ^ Wayne D. LeBaron (1998). America's nuclear legacy. Nova Publishers. p. 29. ISBN 978-1-56072-556-5. 42. ^ a b Barton C. Hacker (1994). Elements of controversy: the Atomic Energy Commission and radiation safety in nuclear weapons testing, 1947–1974. University of California Press. ISBN 978-0-520-08323-3. 43. ^ A. Costandina Titus (2001). Bombs in the backyard: atomic testing and American politics. University of Nevada Press. p. 65. ISBN 978-0-87417-370-3. 44. ^ a b Thomas D. Luckey (1991). Radiation hormesis. CRC Press. p. 143. ISBN 978-0-8493-6159-3. 45. ^ Robert J. Ursano; Ann E. Norwood; Carol S. Fullerton (2004). Bioterrorism: psychological and public health interventions. Cambridge University Press. p. 174. ISBN 978-0-521-81472-0. 46. ^ Burguieres TH, Stair T, Rolnick MA, Mossman KL (1980). "Accidental beta radiation burns from an electron accelerator". Annals of Emergency Medicine. 9 (7): 371–3. doi:10.1016/S0196-0644(80)80115-6. PMID 7396251. 47. ^ J. B. Brown; Fryer, MP (1965). "High Energy Electron Injury from Accelerator Machines (Cathode Rays): Radiation Burns of Chest Wall and Neck: 17-Year Follow Up of Atomic Burns". Annals of Surgery. 162 (3): 426–37. doi:10.1097/00000658-196509000-00012. PMC 1476928. PMID 5318671. 48. ^ Of The Army, United States. Dept (1982). Nuclear handbook for medical service personnel. 49. ^ Palmer JL, Deburghgraeve CR, Bird MD, Hauer-Jensen M, Kovacs EJ (2011). "Development of a combined radiation and burn injury model". J Burn Care Res. 32 (2): 317–23. doi:10.1097/BCR.0b013e31820aafa9. PMC 3062624. 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PMID 15080238. ## External links[edit] Classification D * ICD-10: L58 * ICD-9-CM: 692.82 * MeSH: D011855 * ARRL: RF Exposure Safety * FCC: Radio Frequency Safety FAQ * v * t * e Radiation-related disorders / Photodermatoses Ultraviolet/ionizing * Sunburn * Phytophotodermatitis * Solar urticaria * Polymorphous light eruption * Benign summer light eruption * Juvenile spring eruption * Acne aestivalis * Hydroa vacciniforme * Solar erythema Non-ionizing Actinic rays * Actinic keratosis * Atrophic actinic keratosis * Hyperkeratotic actinic keratosis * Lichenoid actinic keratosis * Pigmented actinic keratosis * Actinic cheilitis * Actinic granuloma * Actinic prurigo * Chronic actinic dermatitis Infrared/heat * Erythema ab igne (Kangri ulcer * Kairo cancer * Kang cancer * Peat fire cancer) * Cutis rhomboidalis nuchae * Poikiloderma of Civatte Other * Radiation dermatitis * Acute * Chronic radiodermatitis) * Favre–Racouchot syndrome * Photoaging * Photosensitivity with HIV infection * Phototoxic tar dermatitis * v * t * e Consequences of external causes Temperature Elevated Hyperthermia Heat syncope Reduced Hypothermia Immersion foot syndromes Trench foot Tropical immersion foot Warm water immersion foot Chilblains Frostbite Aerosol burn Cold intolerance Acrocyanosis Erythrocyanosis crurum Radiation Radiation poisoning Radiation burn Chronic radiation keratosis Eosinophilic, polymorphic, and pruritic eruption associated with radiotherapy Radiation acne Radiation-induced cancer Radiation recall reaction Radiation-induced erythema multiforme Radiation-induced hypertrophic scar Radiation-induced keloid Radiation-induced morphea Air * Hypoxia/Asphyxia * Barotrauma * Aerosinusitis * Decompression sickness * High altitude * Altitude sickness * Chronic mountain sickness * Death zone * HAPE * HACE Food * Starvation Maltreatment * Physical abuse * Sexual abuse * Psychological abuse Travel * Motion sickness * Seasickness * Airsickness * Space adaptation syndrome Adverse effect * Hypersensitivity * Anaphylaxis * Angioedema * Allergy * Arthus reaction * Adverse drug reaction Other * Electrical injury * Drowning * Lightning injuries Ungrouped skin conditions resulting from physical factors * Dermatosis neglecta * Pinch mark * Pseudoverrucous papules and nodules * Sclerosing lymphangitis * Tropical anhidrotic asthenia * UV-sensitive syndrome environmental skin conditions Electrical burn frictional/traumatic/sports Black heel and palm Equestrian perniosis Jogger's nipple Pulling boat hands Runner's rump Surfer's knots Tennis toe Vibration white finger Weathering nodule of ear Wrestler's ear Coral cut Painful fat herniation Uranium dermatosis iv use Skin pop scar Skin track Slap mark Pseudoacanthosis nigricans Narcotic dermopathy * Nuclear technology 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-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Radiation burn	c1504534	25,609	wikipedia	https://en.wikipedia.org/wiki/Radiation_burn	2021-01-18T18:32:41	{"mesh": ["D011855"], "umls": ["C0034561", "C1504534"], "icd-9": ["692.82"], "icd-10": ["L58"], "wikidata": ["Q658873"]}
A number sign (#) is used with this entry because of evidence that autosomal recessive limb-girdle muscular dystrophy-10 (LGMDR10) is caused by homozygous or compund heterozygous mutation in the titin gene (TTN; 188840) on chromosome 2q31. Heterozygous mutation in the titin gene causes tardive tibial muscular dystrophy (TMD; 600334). For a general description and a discussion of genetic heterogeneity of autosomal recessive limb-girdle muscular dystrophy, see LGMDR1 (253600). Nomenclature According to the report of the 105th ENMC workshop, the phenotype of the homozygous TTN gene mutation is termed 'LGMD2J' (Bushby and Beckmann, 2003). At the 229th ENMC international workshop, Straub et al. (2018) reviewed, reclassified, and/or renamed forms of LGMD. The proposed naming formula was 'LGMD, inheritance (R or D), order of discovery (number), affected protein.' Under this formula, LGMD2J was renamed LGMDR10. Clinical Features Udd et al. (1991, 1992) reported a large consanguineous Finnish pedigree in which 12 members had mild late-onset distal tibial myopathy (see TMD) inherited in an autosomal dominant pattern and 8 members had a severe limb-girdle muscular dystrophy inherited in an autosomal recessive pattern. Both groups had nonspecific myopathic changes on muscle biopsy and progressive fatty infiltration of involved muscles. Onset of the severe LGMD phenotype was in the first to third decades and involved weakness of all proximal muscles. Severe disability with loss of ambulation occurred within 20 years (third to sixth decades). There was no facial muscle involvement or cardiomyopathy. Some patients later developed distal muscle involvement. Segregation analysis showed that the corrected proportion of affected persons with the severe proximal type was 0.246 and the proportion of affected persons with the distal myopathy was 0.58. The findings were compatible with the hypothesis that the severe LGMD phenotype was the homozygous manifestation of a dominant gene that in the heterozygous state caused the milder distal myopathy (Udd, 1992). In muscle biopsies from a patient with limb-girdle muscular dystrophy who was homozygous for a TMD haplotype, Haravuori et al. (2001) found almost complete loss of calpain-3 (CAPN3; 114240), a ligand of titin. The authors concluded that the loss of calpain-3 is a secondary downstream effect of deficiency of the TMD gene protein and results in phenotypic overlap with LGMDR1, which is caused by mutation in the calpain-3 gene. Dabby et al. (2015) reported a 29-year-old man of Romanian and Hungarian descent who presented with slowly progressive proximal muscle weakness of the lower limbs resulting in difficulty climbing stairs and getting up from a seated position. He also had mild weakness of the shoulder girdle muscles. Laboratory studies showed increased serum creatine kinase, a myopathic and irritative pattern on EMG, nonspecific myopathic changes on muscle biopsy, including variability in fiber size, necrotic and regenerating fibers, and a lymphocytic infiltrate, and fatty replacement of muscles of the lower limb on MRI. He was treated with various immunomodulatory medications with no improvement. Muscle biopsy showed some reduction of C-terminal titin compared to controls, but it was not as severe as had been reported in other patients. Zheng et al. (2016) reported 3 adult sibs from a consanguineous Han Chinese family with LGMDR10. The patients presented between 13 and 16 years of age with difficulty running and climbing, frequent falls, and Gower sign. They developed proximal muscle weakness and atrophy affecting the lower and upper limbs. The disorder was progressive, and they developed elbow and ankle joint contractures; none was able to walk or raise their arms above their shoulders after their thirties. One patient also had lordosis. Skeletal muscle biopsy of 1 patient showed variation in fiber diameter, cell necrosis, fibrosis, and some regenerating fibers. Serum creatine kinase was increased in 2 patients. There was no cardiac involvement. Inheritance The transmission pattern of LGMDR10 in the family reported by Dabby et al. (2015) was consistent with autosomal recessive inheritance. Mapping By genomewide scan of the large Finnish family with LGMD and TMD reported by Udd et al. (1992), Haravuori et al. (1997, 1998) found a region of interest on 2q. Further analyses with additional family members and additional families with TMD, yielded a maximum multipoint lod score of 12.4 with marker D2S324. Haplotype analysis revealed the same core haplotype in all analyzed families, providing evidence for an ancestral mutation, further restricting the critical chromosomal region to about 1 cM, and mapping the disease locus to chromosome 2q31. Three patients with the more severe LGMD phenotype were homozygous for the haplotype, whereas those with the milder TMD phenotype were heterozygous. Molecular Genetics In patients with LGMD2J from the large Finnish family reported by Udd et al. (1992), Hackman et al. (2002) identified homozygosity for an 11-bp deletion/insertion in the last exon (exon 363) of the TTN gene (188840.0004). Family members affected with the milder adult-onset TMD phenotype were heterozygous for the TTN deletion. In a 29-year-old man of Romanian and Hungarian origin with a relatively mild form of LGMDR10, Dabby et al. (2015) identified compound heterozygous missense mutations at conserved residues in the TTN gene: K26320T (188840.0017) and A6135G (188840.0018). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variants were not performed, but patient skeletal muscle biopsy showed a reduction in C-terminal titin compared to controls. In 3 sibs from a consanguineous Han Chinese family with LGMDR10, Zheng et al. (2016) identified a homozygous missense mutation in the TTN gene (W35930R; 188840.0019). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed. INHERITANCE \- Autosomal recessive CARDIOVASCULAR Heart \- No cardiomyopathy MUSCLE, SOFT TISSUES \- Proximal muscle weakness \- Distal muscle weakness, mild \- Upper and lower limbs affected \- Muscle atrophy \- No facial muscle involvement \- Myopathic changes seen on EMG \- Dystrophic changes seen on muscle biopsy \- Fatty infiltration of affected muscles \- Secondary decrease of calpain-3 (CAPN3, 114240 ) protein expression in muscle LABORATORY ABNORMALITIES \- Normal or increased serum creatine kinase MISCELLANEOUS \- Childhood or young adult-onset \- Progressive disorder \- Variable severity \- Loss of ambulation between third and sixth decade (in most patients) MOLECULAR BASIS \- Caused by mutation in the titin gene (TTN, 188840.0004 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 10	c1837342	25,610	omim	https://www.omim.org/entry/608807	2019-09-22T16:07:08	{"doid": ["0110283"], "mesh": ["C563854"], "omim": ["608807"], "orphanet": ["140922"], "synonyms": ["Alternative titles", "MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 2J"]}
A number sign (#) is used with this entry because of evidence that the EVEN-plus syndrome, involving the epiphyses, vertebrae, ears, and nose, plus associated findings, is caused by homozygous or compound heterozygous mutation in the HSPA9 gene (600548) on chromosome 5q31. Description EVEN-PLUS syndrome is characterized by prenatal-onset short stature, vertebral and epiphyseal changes, microtia, midface hypoplasia with flat nose and triangular nares, cardiac malformations, and other findings including anal atresia, hypodontia, and aplasia cutis. The features overlap those reported in patients with CODAS syndrome (600373; Royer-Bertrand et al., 2015). Clinical Features Amiel et al. (1999) reported 2 sisters, born to distantly related Algerian parents, who exhibited epiphyseal, vertebral, and ear dysplasia, but had normal stature and psychomotor development. Their facial features were strikingly similar and included flat face, high forehead, depressed nasal bridge, short nose with anteverted nares, midface hypoplasia, and prominent philtrum. Both had dysplastic ears, with hypoplastic helices and antihelices. Passive joint mobility was normal, although the younger sister could spontaneously dislocate her elbows, and the older sister had been able to but could no longer do so at age 3.75 years. The older sister also had a unilateral patch of skin aplasia above the ear, and both had short, overriding toes. Radiologic findings included delayed bone age, polyepiphyseal dysplasia, mild metaphyseal dysplasia, persistent midcoronal vertebral clefts, and odontoid hypoplasia. Cardiac and renal ultrasound were normal. Amiel et al. (1999) noted shared features with CODAS syndrome, including delayed bone age, epiphyseal dysplasia, and vertebral clefts, as well as midface hypoplasia, anteverted nares, and ear anomalies. However, the sisters did not exhibit other features of CODAS syndrome such as neonatal hypotonia, postnatal growth retardation, mental retardation, and eye and dental anomalies. Amiel et al. (1999) proposed the acronym 'EVE' for this syndrome involving epiphyseal, vertebral, and ear dysplasia. Royer-Bertrand et al. (2015) reported 2 Chilean sisters, born to consanguineous parents, who were very short at birth with short long bones, in whom x-rays showed dysplasia of the femoral heads, acetabula, and epiphyses at the knees, and bifid distal femurs. The younger sister also had vertebral coronal clefts and agenesis of the coccyx. Dysmorphic features included hypoplasia of the midface and nasal bones, resulting in a flat nose with triangular nares, as well as arched eyebrows with synophrys and severe microtia or anotia. Both sisters had a small area of aplasia cutis on the vertex of the skull, and the older sister also had 2 lateral hair whorls. Other features included atrial septal defect in the older sister and patent foramen ovale and aneurysmal septum in the younger; the younger sister also had hypodontia, vesicoureteral reflux with hypoplastic right kidney, imperforate anus, developmental delay, and agenesis of the corpus callosum on brain MRI. Royer-Bertrand et al. (2015) also described a Korean girl with similar bone findings and facial dysmorphism, including anotia. Other features included an atrial septal defect that closed spontaneously by age 20 months, anal atresia, atopic dermatitis, and sparse hair. Psychomotor development was borderline normal, and brain MRI was normal at age 5 months. The authors noted that the skeletal features in these patients were the same as those seen in patients with CODAS syndrome, but stated that the additional features such as prenatal-onset short stature, the craniofacial phenotype with microtia, flat facial profile with flat nose and triangular nares, cardiac malformations, and other findings such as anal atresia, hypodontia, and aplasia cutis distinguished this disorder. Noting similarities to the sisters described by Amiel et al. (1999), Royer-Bertrand et al. (2015) designated this syndrome 'EVEN-plus,' for epiphyseal, vertebral, ear, and nose involvement, plus associated findings. Molecular Genetics In 2 Chilean sisters and a Korean girl with EVEN-plus syndrome, who were negative for mutation in the LONP1 gene (605490), Royer-Bertrand et al. (2015) performed exome sequencing and identified mutations in the HSPA9 gene (600548) in all 3 patients: the 2 sisters were homozygous for a missense mutation (R126W; 600548.0003), whereas the Korean girl was compound heterozygous for a missense (Y128C; 600548.0004) and a nonsense mutation (V296X; 600548.0005). INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature, prenatal onset HEAD & NECK Head \- Aplasia cutis congenita on skull vertex \- Brachycephaly Face \- Midface hypoplasia Ears \- Severe microtia or anotia, with open ear ducts Eyes \- Arched eyebrows \- Synophrys Nose \- Hypoplastic nose \- Bifid tip of nose \- Triangular nares Mouth \- High palate Teeth \- Single upper central incisor \- Absence of some lateral incisors Neck \- Short neck CARDIOVASCULAR Heart \- Atrial septal defect, small \- Patent foramen ovale \- Aneurysmal septum ABDOMEN Gastrointestinal \- Anal atresia GENITOURINARY Kidneys \- Hypoplastic kidney Ureters \- Vesicoureteral reflux Bladder \- Urinary tract infection SKELETAL Skull \- Brachycephaly Spine \- Coronal vertebral clefts \- Agenesis of the coccyx Pelvis \- Dysplastic acetabula Limbs \- Short long bones \- Dysplastic femoral heads \- Bifid distal femurs \- Epiphyseal dysplasia of distal femur \- Epiphyseal dysplasia of proximal tibia \- Lateral dislocation of patellae SKIN, NAILS, & HAIR Skin \- Aplasia cutis congenita on skull vertex \- Atopic dermatitis Hair \- Sparse hair \- Lateral hair whorls NEUROLOGIC Central Nervous System \- Developmental delay, mild to moderate \- Agenesis of corpus callosum \- Separated frontal horns MISCELLANEOUS \- Based on report of 3 patients from 2 families (last curated March 2016) MOLECULAR BASIS \- Caused by mutation in the heat-shock 70-kd protein-9 gene (HSPA9, 600548.0003 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	EVEN-PLUS SYNDROME	c4225180	25,611	omim	https://www.omim.org/entry/616854	2019-09-22T15:47:44	{"omim": ["616854"], "orphanet": ["496751"], "synonyms": ["EPIPHYSEAL AND VERTEBRAL DYSPLASIA, MICROTIA, AND FLAT NOSE, PLUS ASSOCIATED MALFORMATIONS", "Alternative titles", "Epiphysial-vertebral-ear dysplasia-nose-plus associated findings syndrome"]}
## Clinical Features Hardikar et al. (1992) reported 2 unrelated girls with obstructive hepatic cholestasis and cholangitis associated with cleft lip/palate, hydronephrosis/hydroureter, retinal pigmentation, and intestinal septum. The features were apparent at birth. Both patients had recurrent urinary tract infections, early onset of jaundice, and poor weight gain. Both also developed hepatomegaly and pruritus. Nydegger et al. (2008) reported long-term follow-up of the patients reported by Hardikar et al. (1992). The first patient had cleft lip and palate, pigmentary retinopathy, aortic coarctation, vesicoureteric reflux, obstructive liver disease, and malrotation of the gut. Liver biopsy showed ductal proliferation with hepatic artery hypertrophy. She developed recurrent obstructive jaundice that required surgical intervention at age 13 years. The second patient was born by artificial insemination by donor sperm. She had cleft soft palate, pigmentary retinopathy, hydroureters with distal obstruction, jejunal septum, patent foramen ovale, and mild pulmonary artery stenosis. Liver biopsy showed multiple cystic dilations of the intrahepatic ducts and stenosis of the common bile duct. She required liver transplantation at age 15 years. Cognition in both patients was normal. Hardikar et al. (1992) commented on the multiple tubular stenoses apparent in these patients. Nydegger et al. (2008) noted that the syndrome resembled the Kabuki (147920) and Alagille (ALGS1; 118450) syndromes. Cools and Jaeken (1997) reported an infant girl with Hardikar syndrome. She had cleft lip and palate, pigmentary retinopathy, hydroureteronephrosis with severe vesicoureteral reflux, cholestasis, and nonrotation of the gut. Liver ultrasound showed dilated intrahepatic bile ducts, and biopsy showed fibrosis with ductal proliferation and inflammatory cells. She also had patent ductus arteriosus and a small ventricular septal defect. Dysmorphic facial features included long narrow palpebral fissures, depressed nasal tip, and preauricular dimples. She was noted to have moderate psychomotor delay at that time, but follow-up by Nydegger et al. (2008) reported normal development at age 11 years. Cools and Jaeken (1997) had noted that the syndrome resembled the Kabuki syndrome. Maluf et al. (2002) reported a girl with features consistent with Hardikar syndrome. She had cleft lip and palate, retinopathy, intestinal malrotation, and recurrent urinary tract infections associated with stenosis of the ureters. She was jaundiced from birth. Liver biopsy showed cirrhosis with regenerating nodules, portal chronic inflammation with bile duct proliferation, and lobular cholestasis. The liver disease was progressive, requiring transplantation at age 24 months. Nydegger et al. (2008) provided follow-up on the girl and noted that she had an excellent clinical course after transplantation and had normal development at age 8 years. Poley and Proud (2008) reported another girl with Hardikar syndrome who had malrotation of the gut, pigmentary retinopathy, patent ductus arteriosus, hydronephrosis, and persistent cholestasis resulting in liver failure and transplant. Additional features included vaginal atresia and a common urogenital sinus. Mild dysmorphic facial features were also noted: a prominent forehead, hypertelorism, small chin, bulbous nose, and preauricular dimples. Poley and Proud (2008) postulated that the constellation of defects correlated with a critical time of organogenesis between 30 and 70 days' gestation. INHERITANCE \- Isolated cases GROWTH Other \- Failure to thrive \- Poor growth HEAD & NECK Ears \- Preauricular dimples \- Hearing impairment, mild (2 patients) Eyes \- Pigmentary retinopathy \- Stippled pigmentation (cat's paw) \- Choroidoretinal degeneration (1 patient) \- Long narrow palpebral fissures (1 patient) Mouth \- Cleft lip \- Cleft palate CARDIOVASCULAR Heart \- Atrial septal defect (1 patient) \- Ventricular septal defect (1 patient) \- Patent foramen ovale (1 patient) Vascular \- Pulmonary artery stenosis (1 patient) \- Patent ductus arteriosus \- Aortic coarctation (1 patient) \- Hypertrophy of branches of the hepatic artery ABDOMEN Liver \- Hepatomegaly \- Obstructive liver disease \- Liver biopsy shows ductal proliferation \- Large duct obstruction \- Ductal plate malformations \- Portal inflammation \- Fibrosis \- Portal hypertension Biliary Tract \- Dilated intrahepatic bile ducts \- Stenosis of common bile duct \- Cholestasis \- Cholangitis Spleen \- Splenomegaly Gastrointestinal \- Intestinal malrotation \- Jejunal web \- Small intestinal septum GENITOURINARY Internal Genitalia (Female) \- Vaginal atresia (1 patient) Kidneys \- Hydronephrosis Ureters \- Ureteral stenosis \- Hydroureter Bladder \- Vesicoureteric reflux \- Recurrent urinary tract infections SKIN, NAILS, & HAIR Skin \- Jaundice \- Pruritus secondary to liver disease NEUROLOGIC Central Nervous System \- Normal cognition LABORATORY ABNORMALITIES \- Hyperbilirubinemia \- Abnormal liver function tests MISCELLANEOUS \- Onset at birth \- Four cases have been reported, all female \- Two patients required liver transplantation ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	HARDIKAR SYNDROME	c0795969	25,612	omim	https://www.omim.org/entry/612726	2019-09-22T16:00:43	{"mesh": ["C535632"], "omim": ["612726"], "orphanet": ["1415"]}
'Near-head,' intermediate, and 'flare' types can be recognized. The data of Kloepfer (1946) suggested complex genetics. Inheritance \- ? Autosomal dominant \- probably complex genetics Ears \- Near-head, intermediate, or flared ears ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	EAR FLARE	c1851902	25,613	omim	https://www.omim.org/entry/128400	2019-09-22T16:42:00	{"omim": ["128400"]}
A mixed tumor is a tumor that derives from multiple tissue types.[1] A biplastic tumor or biphasic tumor has two tissue types.[2][3] ## Contents * 1 True versus false * 2 Number of cell types * 3 Examples of true mixed tumors * 4 References ## True versus false[edit] * A true mixed tumor contains multiple types of neoplastic cells.[4] Some sources require the included tissue types to be neoplastic for the definition of mixed tumor.[1] * A "false" mixed tumor contains one type of neoplastic cells, but which have more than one appearance. For example, benign pleomorphic salivary gland tumors may have some tumors cells that form pseudocartilage. Yet, all the tumor cells have similar myoepithelial profile on immunohistochemistry, and are thus classified as one cell type. Reactive or adaptive changes to a tumor does not count towards a classification as mixed. Such changes include angiogenesis (blood vessel proliferation) and/or desmoplasia (proliferation of connective tissue).[5] ## Number of cell types[edit] * A biplastic tumor or biphasic tumor consists of two tissue types.[2][3] * A teratoma is the main tumor type that often includes more than two tissue types. They may form for example hair, muscle, teeth, and/or bone.[6] ## Examples of true mixed tumors[edit] Carcinosarcoma, a malignant mixed tumor. Disease Cellular elements Fibroadenoma[7] Epithelium Stroma Ceruminous adenoma[8] Inner luminal secretory cells Myoepithelial cells Carcinosarcoma[9] Carcinomatous cells Sarcomatous cells ## References[edit] 1. ^ a b "mixed tumor". TheFreeDictionary (by Farlex). Retrieved 2020-04-26. In turn citing: -For requiring neoplastic types: Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health, Seventh Edition \- Without further specification: \- Farlex Partner Medical Dictionary 2. ^ a b Santosh, Arvind Babu Rajendra (2014). "Histogenetic Concepts, Terminology and Categorization of Biphasic Tumours of the Oral and Maxillofacial Region". Journal of Clinical and Diagnostic Research. 8 (2): 266–70. doi:10.7860/JCDR/2014/7506.4078. ISSN 2249-782X. PMC 3972583. PMID 24701553. 3. ^ a b "Fibroadenoma". Patholines.org. This page was last edited on 4 November 2019 4. ^ Fowler, Melissa H; Fowler, Jason; Ducatman, Barbara; Barnes, Leon; Hunt, Jennifer L (2006). "Malignant mixed tumors of the salivary gland: a study of loss of heterozygosity in tumor suppressor genes". Modern Pathology. 19 (3): 350–355. doi:10.1038/modpathol.3800533. ISSN 0893-3952. 5. ^ Miller, Daniel D; Emley, Andrew; Yang, Shi; Richards, Joanna E; Lee, Jung Eun; Deng, April; Hoang, Mai P; Mahalingam, Meera (2011). "Mixed versus pure variants of desmoplastic melanoma: a genetic and immunohistochemical appraisal". Modern Pathology. 25 (4): 505–515. doi:10.1038/modpathol.2011.196. ISSN 0893-3952. 6. ^ "NCI Dictionary of Cancer Terms". National Cancer Institute. 2011-02-02. Retrieved 20 December 2017. 7. ^ Tavassoli, F.A.; Devilee, P., eds. (2003). World Health Organization Classification of Tumours: Pathology & Genetics: Tumours of the breast and female genital organs. Lyon: IARC Press. ISBN 978-92-832-2412-9. 8. ^ Thompson LD, Nelson BL, Barnes EL (Mar 2004). "Ceruminous adenomas: a clinicopathologic study of 41 cases with a review of the literature". Am J Surg Pathol. 28 (3): 308–18. doi:10.1097/00000478-200403000-00003. PMID 15104293. 9. ^ M Sherif Said. "Pathology of True Malignant Mixed Tumor (Carcinosarcoma)". Medscape. Updated: Dec 01, 2015 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Mixed tumor	c1368354	25,614	wikipedia	https://en.wikipedia.org/wiki/Mixed_tumor	2021-01-18T18:53:24	{"umls": ["C1368354"], "wikidata": ["Q6884024"]}
Cor triatriatum sinister (CTS) results when the left atrium is divided into two compartments by a membrane. The membrane can vary in size and shape and may have one or more openings. Severe cases of cor triatriatum sinister usually present in infancy and are often associated with other heart defects. In less severe cases, the diagnosis may not be made until later in life. The specific symptoms depend on the degree to which the membrane obstructs the flow of blood and whether or not there are additional heart defects. Symptoms may range from mild shortness of breath during exercise to signs of heart failure and lung congestion. Some people with CTS may not have symptoms. Treatment varies according to the severity of the symptoms. For symptomatic patients, surgery is generally considered the definitive course of therapy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Cor triatriatum sinister	c0344712	25,615	gard	https://rarediseases.info.nih.gov/diseases/12484/cor-triatriatum-sinister	2021-01-18T18:01:05	{"orphanet": ["99099"], "synonyms": ["Divided left atrium", "Cor triatriatum sinistrum"]}
Juvenile temporal arteritis (JTA) is an extremely uncommon vasculitis of unknown etiology. Eleven documented cases have been reported in the literature, affecting older children and young adults. In contrast to the classic form of temporal arteritis, it is not a systemic disease nor does it cause local symptoms at the temporal area. The term JTA was coined by Lie and his colleagues, in 1975, when they reported four cases of an otherwise asymptomatic disease presenting with a painless nodule at the temporal region. None of the cases showed evidence of systemic disease or history of trauma to the temporal region. Excisional biopsy of the lesions revealed a non-giant cell granulomatous inflammation of the temporal arteries with eosinophilic infiltration, intimal proliferation and microaneurysmal disruption of the media. JTA has a benign clinical course, is treated by surgical excision and does not recur. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Juvenile temporal arteritis	c0751547	25,616	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=26137	2021-01-23T18:23:04	{"gard": ["3068"], "mesh": ["D013700"], "umls": ["C0751547"], "icd-10": ["L95.8"], "synonyms": ["JTA", "Non-giant cell granulomatous temporal arteritis with eosinophilia"]}
A number sign (#) is used with this entry because it represents a contiguous gene deletion syndrome on chromosome 15q15.3. Two of the genes residing in this region are STRC (606440) and CATSPER2 (607249). STRC alterations cause autosomal recessive nonsyndromic sensorineural deafness-16 (DFNB16; 603720). Description Deafness-infertility syndrome (DIS), characterized by early-onset deafness in both males and females and exclusive male infertility, is caused by homozygous deletion of the STRC and CATSPER2 genes on chromosome 15q15.5 (summary by Vona et al., 2015). Clinical Features Dgany et al. (2002) reported a nonconsanguineous French family in which a 56-year-old male and his 2 brothers suffered from type I congenital dyserythropoietic anemia (CDA1; 224120), infertility, and nonsyndromic deafness. Further examination of the 3 brothers by Avidan et al. (2003) revealed a moderate symmetric sensorineural hearing loss of 40 dB involving all frequencies. Semen analysis showed a normal volume and sperm concentration but abnormal motility and morphology, indicative of asthenoteratozoospermia. Zhang et al. (2007) described 3 consanguineous unrelated Iranian families segregating autosomal recessive nonsyndromic deafness. In each family, affected individuals had prelingual auditory impairment with normal vestibular function and no syndromic features. Sperm motility was assessed in 3 males from 2 of the families, and all 3 had reductions in motility and viability consistent with asthenoteratozoospermia; in the third family, the only affected male was too young to assess. Knijnenburg et al. (2009) described a 10-year-old boy, born of nonconsanguineous parents, who had progressive bilateral sensorineural hearing loss with moderate hearing impairment for all frequencies. He had mental retardation, short stature, normal head circumference, and dysmorphic features consisting of metopic ridge, low set ears, high nasal bridge and protruding columella, high-arched palate, small palpebral fissures, thick eyelashes, and synophrys. He also displayed brachydactyly and had intermittent swelling of hands and feet with no known cause. Vona et al. (2015) reported 3 patients, including 2 boys and a girl, with onset of sensorineural deafness between birth and early childhood. All had homozygous deletions of the STRC and CATSPER2 genes. All were prepubertal at the time of study and were not evaluated for fertility. One boy had additional congenital abnormalities and comorbidities, which were likely independent of the deafness. The patients were ascertained from a larger cohort of 94 GJB2 (121011)/GJB6 (604418)-negative pediatric patients with sensorineural hearing loss who underwent genetic analysis. Mapping Zhang et al. (2007) performed a genomewide screen using STRP marker analysis in 2 consanguineous unrelated Iranian families with deafness and male infertility and identified a single region of homozygosity by descent in affected individuals on chromosome 15q15.1-q15.3. Molecular Genetics In 3 French brothers with type I CDA, asthenoteratozoospermia, and nonsyndromic deafness, Dgany et al. (2002) identified homozygosity for a point mutation within the codanin gene (607465.0003) as the cause of the type I CDA. Avidan et al. (2003) found that the 3 sibs were also homozygous for an approximately 70-kb deletion in chromosome 15q15, which removed the entire STRC gene and the last 2 exons (225 bp) of the CATSPER2 gene. Avidan et al. (2003) suggested that lack of functional stereocilin, which is mutated in DFNB16 (603720), and CATSPER2, a voltage-gated cation channel expressed exclusively in spermatozoa, might explain the observed deafness and male infertility phenotypes, respectively. In 3 consanguineous Iranian families segregating nonsyndromic deafness and male infertility, Zhang et al. (2007) identified an approximately 100-kb deleted region on chromosome 15q15.3 involving KIAA0377 (610979), CKMT1B (123290), STRC, and CATSPER2. The families did not share identical deletions, and haplotype analysis indicated that they did not share a common ancestor. Zhang et al. (2007) noted that the hearing loss phenotype in these families was similar by audioprofiling to that of DFNB16, suggesting that deletion of STRC is causally related to their deafness. In a 10-year-old boy, born of nonconsanguineous parents, who had progressive bilateral sensorineural hearing loss, mental retardation, and dysmorphic features, Knijnenburg et al. (2009) identified homozygosity for a 90-kb deletion on chromosome 15q15.3, containing 4 genes, including the STRC gene. The unaffected parents were hemizygous carriers. By screening healthy control individuals and reviewing publicly available copy number variation (CNV) data, Knijnenburg et al. (2009) estimated the frequency of hemizygous deletion carriers to be about 1.6%. The authors noted that this case illustrates the importance of not automatically eliminating registered CNVs from further analysis. INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Hearing loss, sensorineural (bilateral, prelingual) GENITOURINARY Internal Genitalia (Male) \- Asthenoteratozoospermia MOLECULAR BASIS \- A contiguous gene syndrome caused by deletion of the stereocilin gene (STRC, 606440 ) and the sperm-associated cation channel-2 gene (CATSPER2, 607249 ) gene ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	DEAFNESS-INFERTILITY SYNDROME	c1970187	25,617	omim	https://www.omim.org/entry/611102	2019-09-22T16:03:38	{"mesh": ["C567010"], "omim": ["611102"], "orphanet": ["94064"], "synonyms": ["Alternative titles", "DEAFNESS, SENSORINEURAL, AND MALE INFERTILITY", "CHROMOSOME 15q15.3 DELETION SYNDROME"], "genereviews": ["NBK22925"]}
A rare primary bone dysplasia syndrome characterized by growth retardation with proportionate short stature, cortical thickening and medullary stenosis of the long bones, delayed anterior fontanelle closure, hypocalcemia due to congenital hypoparathyroidism and facial dysmorphism, including prominent forehead, microphthalmia, and micrognathia. Additonal manifestations include ocular and dental anomalies (e.g. corneal opacity, hyperopia, optic atrophy, tortuous retinal vessels, dental caries, enamel defects) and, occasionally, hypoplastic nails and neonatal liver disease. Inheritance may be autosomal dominant or autosomal recessive, with more severe growth retardation, small hands and feet, intellectual disability, microcephaly and recurrent bacterial infections being observed in the latter. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Kenny-Caffey syndrome	c0265291	25,618	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2333	2021-01-23T18:34:48	{"mesh": ["C537020"], "omim": ["127000", "244460"], "umls": ["C0265291"], "icd-10": ["Q87.1"], "synonyms": ["Kenny syndrome"]}
Mucoepidermoid carcinoma is a type of cancer of the salivary glands. Salivary gland cancer is diagnosed in 2-3 individuals per 100,000 people each year, and 30-35% of these are mucoepidermoid carcinomas. Mucoepidermoid carcinoma develops when a cell randomly acquires changes (mutations) in genes that regulate how the cell divides such that it begins to grow quickly, forming a cluster of cells (a mass or lump). The earliest signs of a mucoepidermoid carcinoma may include a lump in the face, neck, or mouth; numbness, weakness, or pain in part of the face; or difficulty swallowing. Treatment often begins with surgery to remove the entire tumor. In some cases, radiation therapy and/or chemotherapy may be used after surgery to ensure that no cancer cells remain in the body. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Mucoepidermoid carcinoma	c0206694	25,619	gard	https://rarediseases.info.nih.gov/diseases/10671/mucoepidermoid-carcinoma	2021-01-18T17:58:57	{"mesh": ["D018277"], "umls": ["C0206694"], "synonyms": ["C3772"]}
Complete androgen insensitivity syndrome is a condition that affects sexual development before birth and during puberty. People with this condition are genetically male (one X and one Y chromosome) but do not respond to male hormones at all. As a result, they generally have normal female external genitalia and female breasts. However, they do not have a uterus or cervix so are unable to menstruate or conceive children. Other signs and symptoms may include undescended testes and sparse to absent pubic hair. Gender identity is typically female. Complete androgen insensitivity syndrome is caused by changes (mutations) in the AR gene and is inherited in an X-linked manner. Treatment and gender assignment can be a very complex issue, and must be individualized with each affected person. In general, surgery may be required to remove testes that are located in unusual places and estrogen replacement therapy can be prescribed after puberty. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Complete androgen insensitivity syndrome	c0936016	25,620	gard	https://rarediseases.info.nih.gov/diseases/10597/complete-androgen-insensitivity-syndrome	2021-01-18T18:01:12	{"mesh": ["D013734"], "umls": ["C0936016"], "orphanet": ["99429"], "synonyms": ["CAIS", "Androgen insensitivity syndrome, complete"]}
A number sign (#) is used with this entry because of evidence that mucopolysaccharidosis type IX can be caused by compound heterozygous mutation in the HYAL1 gene (607071) on chromosome 3p21. One such patient has been reported. Clinical Features Natowicz et al. (1996) described the clinical, pathologic, and biochemical findings in a child with short stature and multiple periarticular soft-tissue masses who proved to have a storage disease of hyaluronan (hyaluronic acid) due to a genetic deficiency of hyaluronidase. Genetic deficiencies of most of the lysosomal enzymes that catalyze the degradation of glycosaminoglycans had been previously identified, with the exception of hyaluronidase, a lysosomal endoglycosidase that catalyzes the degradation of hyaluronan. The patient was a 14-year-old girl who had a normal early medical history except for frequent episodes of otitis media and a 'ganglion' that had been excised from her left wrist when she was 6 months old. At the age of 7.5 years, a soft-tissue mass over the lateral aspect of her left ankle had been removed. During the next year, additional periarticular masses developed involving the proximal right second finger, the left popliteal fossa, the left inferior patella, and the right and left lateral malleoli. At the age of 9.5 years, the patient had the first of several episodes of transient, painful swelling of the periarticular masses, and generalized cutaneous swelling. These episodes accompanied or followed exertion or a febrile illness and were self-limited, resolving spontaneously within a period of 72 hours. Between the ages of 8.5 and 14 years, her growth rate declined from about the 15th percentile to below the 5th percentile, some of the periarticular masses enlarged, and new masses and right-foot pain developed. She was 145.5 cm tall (less than 5th percentile) at the age of 14 years. Natowicz et al. (1996) noted mildly dysmorphic craniofacial features with a flattened nasal bridge, bifid uvula, and a submucosal cleft palate. There was full range of motion of all joints and no scoliosis, kyphosis, adenopathy, or organomegaly. Magnetic resonance imaging (MRI) of the left knee at the age of 10 years revealed a nodular synovium, a popliteal cyst, and a large joint effusion. Computed tomography (CT) and MRI of hip joints at the age of 12 years demonstrated the presence of masses and erosions and also revealed bilateral joint effusions and a possible cyst of the right trochanteric bursa. The patient had no plasma hyaluronidase activity, and a mixing experiment provided no evidence of an inhibitor of enzyme activity. The plasma hyaluronidase activity of the patient's father and mother was 30% and 53% of normal, respectively, and 2 of her grandparents also had low or intermediate levels of enzyme activity. Plasma concentrations of hyaluronan were very high in the patient, but normal in the father and mother. The descriptions of hyaluronidase deficiency in this family are consistent with autosomal recessive inheritance. Natowicz et al. (1996) noted that plasma hyaluronidase activity was normal in 56 patients with 25 different lysosomal storage disorders, and there was no marked elevation of the plasma hyaluronan concentration in 16 patients with other storage diseases. Natowicz et al. (1996) suggested that the accumulation of nodular aggregates of histiocytes around and in joints may be the result of the failure of catabolism of hyaluronan by hyaluronidase. The histiocytic predominance at these sites might be the result of the hyaluronan-induced aggregation of macrophages. The marked intracellular storage of substrate and macrophages was presumably due to the receptor-mediated internalization of hyaluronan by these cells, in conjunction with the enzymatic deficiency. The lesser involvement of fibroblasts (and of the skin) and, possibly, other tissues may be due to less efficient internalization of hyaluronan, the delivery of hyaluronan to the lymphatic system, or other enzymatic or nonenzymatic degradative pathways. Natowicz et al. (1996) stated: 'It is curious that the periarticular aggregates of histiocytes caused bone erosions detected only the acetabula. Activated macrophages secrete a variety of cytokines that can stimulate localized osteoclastic activity.' Molecular Genetics To determine the molecular basis of MPS IX, Triggs-Raine et al. (1999) analyzed 2 candidate genes tandemly distributed on chromosome 3p21.3 that encode proteins with homology to a sperm protein with hyaluronidase activity. These genes, HYAL1 and HYAL2 (603551), encode 2 distinct lysosomal hyaluronidases with different substrate specificities. They found that the patient with hyaluronidase deficiency originally reported by Natowicz et al. (1996) was a compound heterozygote for 2 mutations in the HYAL1 gene: a 1412G-A mutation that introduced a nonconservative amino acid substitution (glu268 to lys; 607071.0001) in a putative active site residue, and a complex intragenic rearrangement, 1361del37ins14 (607071.0002), that resulted in a premature termination codon. They showed that these 2 hyaluronidase genes, as well as the adjacent HYAL3 gene (604038), had markedly different tissue expression patterns, consistent with differing roles in the metabolism of hyaluronan. The findings in relation to these 3 genes explained the unexpectedly mild phenotype of MPS IX and predicted the existence of other hyaluronidase deficiency disorders. Nomenclature The hyaluronan form of mucopolysaccharidosis is designated mucopolysaccharidosis type IX (MPS9). A form of mucopolysaccharidosis had earlier been designated mucopolysaccharidosis VIII (MPS VIII; MPS8), DiFerrante syndrome, or glucosamine-6-sulfate sulfatase deficiency, but the phenotype was later found to be based on incorrect data (see HISTORY). These designations are no longer used for a form of mucopolysaccharidosis. History Ginsburg et al. (1977) described a patient with a form of mucopolysaccharidosis that combined clinical and biochemical features of the Morquio and Sanfilippo syndromes. The patient was a 5-year-old male with short stature, mental retardation, excessive coarse hair, hepatomegaly, only mild dysostosis multiplex, and hypoplasia of the odontoid. The cornea was unaffected. Both keratan sulfate and heparan sulfate were excreted in the urine. Circulating lymphocytes stained with toluidine blue showed a peculiar ring-shaped metachromasia underlying the cell membrane. Unlike Morquio syndrome, cultured fibroblasts accumulated (35)S and showed delayed wash-out of (35)S. Heparan sulfate and keratan sulfate have in common a sulfated N-acetylglucosamine. Sulfated N-acetylgalactosamine is limited to keratan sulfate. Ginsburg et al. (1977) suspected the existence of 2 hexosamine sulfatases, one (deficient in MPS IV, or Morquio syndrome) specific for sulfate attached to galactosamine, and one specific for sulfate attached to glucosamine. Although they stated that the latter sulfatase was deficient in their patient, DiFerrante (1980) subsequently found that N-acetylglucosamine-6-sulfate sulfatase was normal. Scientific fraud in his laboratory was suspected. The designation for the disorder based on the article by Ginsburg et al. (1977), mucopolysaccharidosis VIII (MPS VIII), was retired and the next-described MPS was designated MPS IX. Growth \- Short stature Mouth \- Bifid uvula \- Submucosal cleft palate Nose \- Flat nasal bridge Skin \- Generalized cutaneous swelling Joints \- Multiple periarticular soft-tissue masses \- Popliteal cyst \- Joint effusion \- Acetabular erosions Inheritance \- Autosomal recessive Misc \- Frequent episodes of otitis media Lab \- Hyaluronidase deficiency \- Elevated plasma hyaluronan ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	MUCOPOLYSACCHARIDOSIS, TYPE IX	c1291490	25,621	omim	https://www.omim.org/entry/601492	2019-09-22T16:14:45	{"doid": ["0050809"], "mesh": ["C563209"], "omim": ["601492"], "orphanet": ["67041"], "synonyms": ["Alternative titles", "MPS IX", "HYALURONIDASE DEFICIENCY"]}
Not to be confused with Wilson's temperature syndrome, an alternative medicine concept. Genetic multisystem copper-transport disease Wilson's disease Other namesWilson disease, hepatolenticular degeneration A brown ring on the edge of the cornea (Kayser–Fleischer ring) is common in Wilson's disease, especially when neurological symptoms are present. SpecialtyGastroenterology SymptomsSwelling of the legs, yellowish skin, personality changes[1] Usual onsetAge 5 to 35[1] CausesGenetic Differential diagnosisChronic liver disease, Parkinson's disease, multiple sclerosis, others[2][3] TreatmentDietary changes, chelating agents, zinc supplements, liver transplant[1] Frequency~1 per 30,000[1] Wilson's disease is a genetic disorder in which excess copper builds up in the body. Symptoms are typically related to the brain and liver. Liver-related symptoms include vomiting, weakness, fluid build up in the abdomen, swelling of the legs, yellowish skin and itchiness. Brain-related symptoms include tremors, muscle stiffness, trouble speaking, personality changes, anxiety, and psychosis.[1] Wilson's disease is caused by a mutation in the Wilson disease protein (ATP7B) gene. This protein transports excess copper into bile, where it is excreted in waste products. The condition is autosomal recessive; for a person to be affected, they must inherit a mutated copy of the gene from both parents. Diagnosis may be difficult and often involves a combination of blood tests, urine tests and a liver biopsy. Genetic testing may be used to screen family members of those affected.[1] Wilson's disease is typically treated with dietary changes and medication. Dietary changes involve eating a low-copper diet and not using copper cookware. Medications used include chelating agents such as trientine and d-penicillamine and zinc supplements. Complications of Wilson's disease can include liver failure, liver cancer and kidney problems. A liver transplant may be helpful in those in whom other treatments are not effective or if liver failure occurs.[1] Wilson's disease occurs in about 1 in 30,000 people.[1] Symptoms usually begin between the ages of 5 and 35 years.[1] It was first described in 1854 by German pathologist Friedrich Theodor von Frerichs and is named after British neurologist Samuel Wilson.[4] ## Contents * 1 Signs and symptoms * 1.1 Liver disease * 1.2 Neuropsychiatric symptoms * 1.3 Other organ systems * 2 Genetics * 3 Pathophysiology * 4 Diagnosis * 4.1 Ceruloplasmin * 4.2 Serum and urine copper * 4.3 Liver biopsy * 4.4 Genetic testing * 5 Treatment * 5.1 Diet * 5.2 Medication * 5.3 Physical and occupational therapies * 5.4 Transplantation * 6 Prognosis * 7 History * 8 Other animals * 9 See also * 10 References * 11 External links ## Signs and symptoms[edit] The main sites of copper accumulation are the liver and the brain, and consequently liver disease and neuropsychiatric symptoms are the main features that lead to diagnosis.[5] People with liver problems tend to come to medical attention earlier, generally as children or teenagers, than those with neurological and psychiatric symptoms, who tend to be in their twenties or older. Some are identified only because relatives have been diagnosed with Wilson's disease; many of these, when tested, turn out to have been experiencing symptoms of the condition but have not received a diagnosis.[6] ### Liver disease[edit] Liver disease may present itself as tiredness, increased bleeding tendency or confusion (due to hepatic encephalopathy) and portal hypertension. The latter, a condition in which the pressure in the portal vein is markedly increased, leads to esophageal varices, blood vessels in the esophagus that may bleed in a life-threatening fashion, as well as enlargement of the spleen (splenomegaly) and accumulation of fluid in the abdominal cavity (ascites). On examination, signs of chronic liver disease such as spider angiomata (small distended blood vessels, usually on the chest) may be observed. Chronic active hepatitis has caused cirrhosis of the liver in most by the time they develop symptoms. While most people with cirrhosis have an increased risk of hepatocellular carcinoma (liver cancer), this risk is relatively very low in Wilson's disease.[5] About 5% of all people are diagnosed only when they develop fulminant acute liver failure, often in the context of a hemolytic anemia (anemia due to the destruction of red blood cells). This leads to abnormalities in protein production (identified by deranged coagulation) and metabolism by the liver. The deranged protein metabolism leads to the accumulation of waste products such as ammonia in the bloodstream. When these irritate the brain, the person develops hepatic encephalopathy (confusion, coma, seizures and finally life-threatening swelling of the brain).[5] ### Neuropsychiatric symptoms[edit] About half the people with Wilson's disease have neurological or psychiatric symptoms. Most initially have mild cognitive deterioration and clumsiness, as well as changes in behavior. Specific neurological symptoms usually then follow, often in the form of parkinsonism (cogwheel rigidity, bradykinesia or slowed movements and a lack of balance are the most common parkinsonian features[7]) with or without a typical hand tremor, masked facial expressions, slurred speech, ataxia (lack of coordination) or dystonia (twisting and repetitive movements of part of the body). Seizures and migraine appear to be more common in Wilson's disease.[5] A characteristic tremor described as "wing-beating tremor" is encountered in many people with Wilson's; this is absent at rest but can be provoked by abducting the arms and flexing the elbows toward the midline.[8] Cognition can also be affected in Wilson's disease. This comes in two, not mutually exclusive, categories: frontal lobe disorder (may present as impulsivity, impaired judgement, promiscuity, apathy and executive dysfunction with poor planning and decision making) and subcortical dementia (may present as slow thinking, memory loss and executive dysfunction, without signs of aphasia, apraxia or agnosia). It is suggested that these cognitive involvements are related and closely linked to psychiatric manifestations of the disease.[7] Psychiatric problems due to Wilson's disease may include behavioral changes, depression, anxiety disorders, and psychosis.[5] Psychiatric symptoms are commonly seen in conjunction with neurological symptoms and are rarely manifested on their own. These symptoms are often poorly defined and can sometimes be attributed to other causes. Because of this, diagnosis of Wilson's disease is rarely made when only psychiatric symptoms are present.[7] ### Other organ systems[edit] Medical conditions have been linked with copper accumulation in Wilson's disease: * Eyes: Kayser–Fleischer rings (KF rings), a pathognomonic sign, may be visible in the cornea of the eyes, either directly or on slit lamp examination as deposits of copper in a ring around the cornea. They are due to copper deposition in Descemet's membrane. These rings can be either dark brown, golden, or reddish-green, are 1 to 3 mm wide, and appear at the corneal limbus. They do not occur in all people with Wilson's disease. Wilson's disease is also associated with sunflower cataracts exhibited by brown or green pigmentation of the anterior and posterior lens capsule.[9] Neither cause significant visual loss.[5] KF rings occur in approximately 66% of diagnosed cases (more often in those with neurological symptoms rather than with liver problems).[6] * Kidneys: renal tubular acidosis (Type 2), a disorder of bicarbonate handling by the proximal tubules leads to nephrocalcinosis (calcium accumulation in the kidneys), a weakening of bones (due to calcium and phosphate loss), and occasionally aminoaciduria (loss of essential amino acids needed for protein synthesis).[5] * Heart: cardiomyopathy (weakness of the heart muscle) is a rare but recognized problem in Wilson's disease; it may lead to heart failure (fluid accumulation due to decreased pump function) and cardiac arrhythmias (episodes of irregular and/or abnormally fast or slow heart beat).[5] * Hormones: hypoparathyroidism (failure of the parathyroid glands leading to low calcium levels), infertility, and recurrent miscarriage.[5] * Sunflower cataract and thick KF ring of a 40-year-old male with Wilson's disease and decompensated CLD * Diffuse illumination of cornea * Copper deposition on corneal Descemet's membrane ## Genetics[edit] Wilson's disease has an autosomal recessive pattern of inheritance. Main article: ATP7B The Wilson's disease gene (ATP7B) is on chromosome 13 (13q14.3) and is expressed primarily in the liver, kidney, and placenta. The gene codes for a P-type (cation transport enzyme) ATPase that transports copper into bile and incorporates it into ceruloplasmin.[5] Mutations can be detected in 90% of cases. Most (60%) are homozygous for ATP7B mutations (two abnormal copies), and 30% have only one abnormal copy. Ten percent have no detectable mutation.[6] Although 300 mutations of ATP7B have been described, in most populations the cases of Wilson's disease are due to a small number of mutations specific for that population. For instance, in Western populations the H1069Q mutation (replacement of a histidine by a glutamine at position 1069 in the protein) is present in 37–63% of cases, while in China this mutation is very uncommon and R778L (arginine to leucine at 778) is found more often. Relatively little is known about the relative impact of various mutations, although the H1069Q mutation seems to predict later onset and predominantly neurological problems, according to some studies.[5][10] A comprehensive clinically annotated resource, WilsonGen provides clinical classification for the variants as per the recent ACMG & AMP guidelines[11] A normal variation in the PRNP gene can modify the course of the disease by delaying the age of onset and affecting the type of symptoms that develop. This gene produces prion protein, which is active in the brain and other tissues and also appears to be involved in transporting copper.[12] A role for the ApoE gene was initially suspected but could not be confirmed.[10] The condition is inherited in an autosomal recessive pattern. In order to inherit it, both of the parents of an individual must carry an affected gene. Most have no family history of the condition.[10] People with only one abnormal gene are called carriers (heterozygotes) and may have mild, but medically insignificant, abnormalities of copper metabolism.[13] Wilson's disease is the most common from a group of hereditary diseases that cause copper overload in the liver. All can cause cirrhosis at a young age. The other members of the group are Indian childhood cirrhosis (ICC), endemic Tyrolean infantile cirrhosis and idiopathic copper toxicosis. These are not related to ATP7B mutations: for example, ICC has been linked to mutations in the KRT8 and the KRT18 gene.[10] ## Pathophysiology[edit] Normal absorption and distribution of copper. Cu = copper, CP = ceruloplasmin, green = ATP7B carrying copper. Copper is needed by the body for a number of functions, predominantly as a cofactor for a number of enzymes such as ceruloplasmin, cytochrome c oxidase, dopamine β-hydroxylase, superoxide dismutase and tyrosinase.[10] Copper enters the body through the digestive tract. A transporter protein on the cells of the small bowel, copper membrane transporter 1 (Ctr1; SLC31A1), carries copper inside the cells, where some is bound to metallothionein and part is carried by ATOX1 to an organelle known as the trans-Golgi network. Here, in response to rising concentrations of copper, an enzyme called ATP7A (Menkes' protein) releases copper into the portal vein to the liver. Liver cells also carry the CMT1 protein, and metallothionein and ATOX1 bind it inside the cell, but here it is ATP7B that links copper to ceruloplasmin and releases it into the bloodstream, as well as removing excess copper by secreting it into bile. Both functions of ATP7B are impaired in Wilson's disease. Copper accumulates in the liver tissue; ceruloplasmin is still secreted, but in a form that lacks copper (termed apoceruloplasmin) and is rapidly degraded in the bloodstream.[10] When the amount of copper in the liver overwhelms the proteins that normally bind it, it causes oxidative damage through a process known as Fenton chemistry; this damage eventually leads to chronic active hepatitis, fibrosis (deposition of connective tissue) and cirrhosis. The liver also releases copper into the bloodstream that is not bound to ceruloplasmin. This free copper precipitates throughout the body but particularly in the kidneys, eyes and brain. In the brain, most copper is deposited in the basal ganglia, particularly in the putamen and globus pallidus (together called the lenticular nucleus); these areas normally participate in the coordination of movement as well as playing a significant role in neurocognitive processes such as the processing of stimuli and mood regulation. Damage to these areas, again by Fenton chemistry, produces the neuropsychiatric symptoms seen in Wilson's disease.[10] It is not clear why Wilson's disease causes hemolysis, but various lines of evidence suggest that a high level of free (non-ceruloplasmin bound) copper has a direct effect on either oxidation of hemoglobin, inhibition of energy-supplying enzymes in the red blood cell, or direct damage to the cell membrane.[14] ## Diagnosis[edit] Location of the basal ganglia, the part of the brain affected by Wilson's disease Wilson's disease may be suspected on the basis of any of the symptoms mentioned above, or when a close relative has been found to have Wilson's. Most have slightly abnormal liver function tests such as a raised aspartate transaminase, alanine transaminase and bilirubin level. If the liver damage is significant, albumin may be decreased due to an inability of damaged liver cells to produce this protein; likewise, the prothrombin time (a test of coagulation) may be prolonged as the liver is unable to produce proteins known as clotting factors.[5] Alkaline phosphatase levels are relatively low in those with Wilson's-related acute liver failure.[15] If there are neurological symptoms, magnetic resonance imaging (MRI) of the brain is usually performed; this shows hyperintensities in the part of the brain called the basal ganglia in the T2 setting.[13] MRI may also demonstrate the characteristic "face of the giant panda" pattern.[16] There is no totally reliable test for Wilson's disease, but levels of ceruloplasmin and copper in the blood, as well of the amount of copper excreted in urine during a 24-hour period, are together used to form an impression of the amount of copper in the body. The gold standard—or most ideal test—is a liver biopsy.[5] ### Ceruloplasmin[edit] Ceruloplasmin Levels of ceruloplasmin are abnormally low (<0.2 g/L) in 80–95% of cases.[5] It can, however, be present at normal levels in people with ongoing inflammation as it is an acute phase protein. Low ceruloplasmin is also found in Menkes disease and aceruloplasminemia, which are related to, but much rarer than Wilson's disease.[5][13] The combination of neurological symptoms, Kayser–Fleischer rings and a low ceruloplasmin level is considered sufficient for the diagnosis of Wilson's disease. In many cases, however, further tests are needed.[13] ### Serum and urine copper[edit] Serum copper is low, which may seem paradoxical given that Wilson's disease is a disease of copper excess. However, 95% of plasma copper is carried by ceruloplasmin which is often low in Wilson's disease. Urine copper is elevated in Wilson's disease and is collected for 24 hours in a bottle with a copper-free liner. Levels above 100 μg/24h (1.6 μmol/24h) confirm Wilson's disease, and levels above 40 μg/24h (0.6 μmol/24h) are strongly indicative.[5] High urine copper levels are not unique to Wilson's disease; they are sometimes observed in autoimmune hepatitis and in cholestasis (any disease obstructing the flow of bile from the liver to the small bowel).[13] In children, the penicillamine test may be used. A 500 mg oral dose of penicillamine is administered, and urine collected for 24 hours. If this contains more than 1600 μg (25 μmol), it is a reliable indicator of Wilson's disease.[clarification needed] This test has not been validated in adults.[13] ### Liver biopsy[edit] Once other investigations have indicated Wilson's disease, the ideal test is the removal of a small amount of liver tissue through a liver biopsy. This is assessed microscopically for the degree of steatosis and cirrhosis, and histochemistry and quantification of copper are used to measure the severity of the copper accumulation. A level of 250 μg of copper per gram of dried liver tissue confirms Wilson's disease. Occasionally, lower levels of copper are found; in that case, the combination of the biopsy findings with all other tests could still lead to a formal diagnosis of Wilson's.[5] In the earlier stages of the disease, the biopsy typically shows steatosis (deposition of fatty material), increased glycogen in the nucleus, and areas of necrosis (cell death). In more advanced disease, the changes observed are quite similar to those seen in autoimmune hepatitis, such as infiltration by inflammatory cells, piecemeal necrosis and fibrosis (scar tissue). In advanced disease, finally, cirrhosis is the main finding. In acute liver failure, degeneration of the liver cells and collapse of the liver tissue architecture is seen, typically on a background of cirrhotic changes. Histochemical methods for detecting copper are inconsistent and unreliable, and taken alone are regarded as insufficient to establish a diagnosis.[13] ### Genetic testing[edit] Mutation analysis of the ATP7B gene, as well as other genes linked to copper accumulation in the liver, may be performed. Once a mutation is confirmed, it is possible to screen family members for the disease as part of clinical genetics family counseling.[5] Regional distributions of genes associated with Wilson's disease are important to follow, as this can help clinicians design appropriate screening strategies. Since mutations of the WD gene vary between populations, research and genetic testing done in countries like the USA or United Kingdom can pose problems as they tend to have more mixed populations.[17] ## Treatment[edit] ### Diet[edit] In general, a diet low in copper-containing foods is recommended with the avoidance of mushrooms, nuts, chocolate, dried fruit, liver, sesame seeds and sesame oil, and shellfish.[5] ### Medication[edit] Medical treatments are available for Wilson's disease. Some increase the removal of copper from the body, while others prevent the absorption of copper from the diet. Generally, penicillamine is the first treatment used. This binds copper (chelation) and leads to excretion of copper in the urine. Hence, monitoring of the amount of copper in the urine can be done to ensure a sufficiently high dose is taken. Penicillamine is not without problems: about 20% experience a side effect or complication of penicillamine treatment, such as drug-induced lupus (causing joint pains and a skin rash) or myasthenia (a nerve condition leading to muscle weakness). In those who presented with neurological symptoms, almost half experience a paradoxical worsening in their symptoms. While this phenomenon is observed in other treatments for Wilson's, it is usually taken as an indication for discontinuing penicillamine and commencing second-line treatment.[5][13] Those intolerant to penicillamine may instead be commenced on trientine hydrochloride, which also has chelating properties. Some recommend trientine as first-line treatment, but experience with penicillamine is more extensive.[13] A further agent, under clinical investigation by Wilson Therapeutics, with known activity in Wilson's disease is tetrathiomolybdate. This is regarded as experimental,[13] though some studies have shown a beneficial effect.[5] Once all results have returned to normal, zinc (usually in the form of a zinc acetate prescription called Galzin) may be used instead of chelators to maintain stable copper levels in the body. Zinc stimulates metallothionein, a protein in gut cells that binds copper and prevents their absorption and transport to the liver. Zinc therapy is continued unless symptoms recur or if the urinary excretion of copper increases.[13] In rare cases where none of the oral treatments are effective, especially in severe neurological disease, dimercaprol (British anti-Lewisite) is occasionally necessary. This treatment is injected intramuscularly (into a muscle) every few weeks and has unpleasant side effects such as pain.[18] People who are asymptomatic (for instance, those diagnosed through family screening or only as a result of abnormal test results) are generally treated, as the copper accumulation may cause long-term damage in the future. It is unclear whether these people are best treated with penicillamine or zinc acetate.[13] ### Physical and occupational therapies[edit] Physiotherapy and occupational therapy are beneficial for patients with the neurologic form of the disease. The copper chelating treatment may take up to six months to start working, and these therapies can assist in coping with ataxia, dystonia, and tremors, as well as preventing the development of contractures that can result from dystonia.[19] ### Transplantation[edit] Liver transplantation is an effective cure for Wilson's disease but is used only in particular scenarios because of the risks and complications associated with the procedure. It is used mainly in people with fulminant liver failure who fail to respond to medical treatment or in those with advanced chronic liver disease. Liver transplantation is avoided in severe neuropsychiatric illness, in which its benefit has not been demonstrated.[5][13] ## Prognosis[edit] Left untreated, Wilson's disease tends to become progressively worse and is eventually fatal. With early detection and treatment, most of those affected can live relatively normal lives. Liver and neurologic damage that occurs prior to treatment may improve, but it is often permanent.[20] ## History[edit] The disease bears the name of the British physician Samuel Alexander Kinnier Wilson (1878–1937), a neurologist who described the condition, including the pathological changes in the brain and liver, in 1912.[21] Wilson's work had been predated by, and drew on, reports from German neurologist Carl Westphal (in 1883), who termed it "pseudosclerosis"; by the British neurologist William Gowers (in 1888);[22] by the Finnish neuropathologist Ernst Alexander Homén (in 1889–1892), who noted the hereditary nature of the disease;[23] and by Adolph Strümpell (in 1898), who noted hepatic cirrhosis.[22] Neuropathologist John Nathaniel Cumings made the link with copper accumulation in both the liver and the brain in 1948.[24] The occurrence of hemolysis was noted in 1967.[25] In 1951, Cumings, and New Zealand neurologist Derek Denny-Brown, working in the United States, simultaneously reported the first effective treatment, using metal chelator British anti-Lewisite .[26][27] This treatment had to be injected but was one of the first therapies available in the field of neurology, a field that classically was able to observe and diagnose but had few treatments to offer.[22][28] The first effective oral chelation agent, penicillamine, was discovered in 1956 by British neurologist John Walshe.[29] In 1982, Walshe also introduced trientine,[30] and was the first to develop tetrathiomolybdate for clinical use.[31] Zinc acetate therapy initially made its appearance in the Netherlands, where physicians Schouwink and Hoogenraad used it in 1961 and in the 1970s, respectively, but it was further developed later by Brewer and colleagues at the University of Michigan.[18][32] The genetic basis of Wilson's disease, and its linkage to ATP7B mutations, was elucidated by several research groups in the 1980s and 1990s.[33][34] ## Other animals[edit] Hereditary copper accumulation has been described in Bedlington Terriers,[35] where it generally only affects the liver. It is due to mutations in the COMMD1 (or MURR1) gene.[36] Despite this findings, COMMD1 mutations could not be detected in humans with non-Wilsonian copper accumulation states (such as Indian childhood cirrhosis) to explain their genetic origin.[37] ## See also[edit] * Copper in health * Menkes syndrome ## References[edit] 1. ^ a b c d e f g h i "Wilson Disease". NIDDK. July 2014. Archived from the original on 2016-10-04. Retrieved 2016-11-06. 2. ^ Lynn, D. Joanne; Newton, Herbert B.; Rae-Grant, Alexander (2004). The 5-minute Neurology Consult. Lippincott Williams & Wilkins. p. 442. ISBN 9780683307238. Archived from the original on 2016-11-07. 3. ^ Sahani, Dushyant V.; Samir, Anthony E. (2016). Abdominal Imaging: Expert Radiology Series (2 ed.). Elsevier Health Sciences. p. 400. ISBN 9780323431613. Archived from the original on 2016-11-07. 4. ^ "Whonamedit - dictionary of medical eponyms". www.whonamedit.com. Archived from the original on 2016-11-07. Retrieved 2016-11-06. 5. ^ a b c d e f g h i j k l m n o p q r s t u v Ala A, Walker AP, Ashkan K, Dooley JS, Schilsky ML (2007). "Wilson's disease". Lancet. 369 (9559): 397–408. doi:10.1016/S0140-6736(07)60196-2. PMID 17276780. S2CID 24663871. 6. ^ a b c Merle U, Schaefer M, Ferenci P, Stremmel W (2007). "Clinical presentation, diagnosis and long‐term outcome of Wilson's disease: a cohort study". Gut. 56 (1): 115–20. doi:10.1136/gut.2005.087262. PMC 1856673. PMID 16709660. 7. ^ a b c Lorincz MT (2010). "Neurologic Wilson's disease" (PDF). Annals of the New York Academy of Sciences. 1184 (1): 173–87. Bibcode:2010NYASA1184..173L. doi:10.1111/j.1749-6632.2009.05109.x. hdl:2027.42/78731. PMID 20146697. S2CID 2989668. 8. ^ Pagonabarraga, J; Goetz, C (2012). Biller, J (ed.). Practical Neurology (4th ed.). Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins Heath. p. 282. ISBN 978-1451142631. 9. ^ Yanoff, Myron; Jay S. Duker (2008). Ophthalmology (3rd ed.). Edinburgh: Mosby. p. 411. ISBN 978-0323057516. 10. ^ a b c d e f g de Bie P, Muller P, Wijmenga C, Klomp LW (November 2007). "Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes". J. Med. Genet. 44 (11): 673–88. doi:10.1136/jmg.2007.052746. PMC 2752173. PMID 17717039. 11. ^ Kumar, Mukesh; Gaharwar, Utkarsh; Paul, Sangita; Poojary, Mukta; Pandhare, Kavita; Scaria, Vinod; Bk, Binukumar (2020-06-03). "WilsonGen a comprehensive clinically annotated genomic variant resource for Wilson's Disease". Scientific Reports. 10 (1): 9037. Bibcode:2020NatSR..10.9037K. doi:10.1038/s41598-020-66099-2. ISSN 2045-2322. PMC 7270127. PMID 32493955. 12. ^ Grubenbecher S, Stüve O, Hefter H, Korth C (2006). "Prion protein gene codon 129 modulates clinical course of neurological Wilson disease". NeuroReport. 17 (5): 549–52. doi:10.1097/01.wnr.0000209006.48105.90. PMID 16543824. S2CID 37186426. 13. ^ a b c d e f g h i j k l m Roberts, Eve A.; Schilsky, Michael L. (2003). "A practice guideline on Wilson disease" (PDF). Hepatology. 37 (6): 1475–92. doi:10.1053/jhep.2003.50252. PMID 12774027. S2CID 263620.[dead link] 14. ^ Lee GR (1999). "Chapter 48: acquired hemolytic anaemias resulting from direct effects of infectious, chemical or physical agents". In Lee GR, Foerster J, Lukens J, et al. (eds.). Wintrobe's clinical hematology. vol 1 (10th ed.). Williams & Wilkins. pp. 1298. ISBN 978-0-683-18242-2. 15. ^ Shaver WA, Bhatt H, Combes B (1986). "Low serum alkaline phosphatase activity in Wilson's disease". Hepatology. 6 (5): 859–63. doi:10.1002/hep.1840060509. PMID 3758940. S2CID 24055787. 16. ^ Das SK, Ray K (September 2006). "Wilson's disease: an update". Nat Clin Pract Neurol. 2 (9): 482–93. doi:10.1038/ncpneuro0291. PMID 16932613. S2CID 205340375. 17. ^ Ferenci, Peter (2006-06-22). "Regional distribution of mutations of the ATP7B gene in patients with Wilson disease: impact on genetic testing". Human Genetics. 120 (2): 151–159. doi:10.1007/s00439-006-0202-5. ISSN 0340-6717. PMID 16791614. S2CID 10124665. 18. ^ a b Walshe JM (July 1996). "Treatment of Wilson's disease: the historical background". QJM. 89 (7): 553–5. doi:10.1093/qjmed/89.7.553. PMID 8759497. 19. ^ Brewer GJ, Askari FK (2005). "Wilson's disease: clinical management and therapy". Journal of Hepatology. 42 (Suppl 1): 13–21. doi:10.1016/j.jhep.2004.11.013. PMID 15777568. 20. ^ "Definition and Facts \| NIDDK". National Institute of Diabetes and Digestive and Kidney Diseases. Retrieved 2019-02-01. 21. ^ Kinnier Wilson SA (1912). "Progressive lenticular degeneration: a familial nervous disease associated with cirrhosis of the liver". Brain. 34 (1): 295–507. doi:10.1093/brain/34.4.295. Archived from the original (PDF) on 2009-09-03. Retrieved 2008-04-09. 22. ^ a b c Robertson WM (February 2000). "Wilson's disease". Arch. Neurol. 57 (2): 276–7. doi:10.1001/archneur.57.2.276. PMID 10681092. 23. ^ Homén EA (1892). "Eine eigenthümliche bei drei Geschwistern auftretende typische Krankheit unter der Form einer progressiven Dementia in Verbindung mit ausgedehnten Gefässveränderungen (wohl Lues hereditaria tarda)". Archiv für Psychiatrie und Nervenkrankheiten. 24: 1–38. 24. ^ Cumings JN (1948). "The copper and iron content of brain and liver in the normal and in hepato-lenticular degeneration". Brain. 71 (Dec): 410–5. doi:10.1093/brain/71.4.410. PMID 18124738. Archived from the original (PDF) on 2009-09-03. Retrieved 2008-04-09. 25. ^ McIntyre N, Clink HM, Levi AJ, Cumings JN, Sherlock S (February 1967). "Hemolytic anemia in Wilson's disease". N. Engl. J. Med. 276 (8): 439–44. doi:10.1056/NEJM196702232760804. PMID 6018274. 26. ^ Cumings JN (March 1951). "The effects of B.A.L. in hepatolenticular degeneration". Brain. 74 (1): 10–22. doi:10.1093/brain/74.1.10. PMID 14830662. 27. ^ Denny-Brown D, Porter H (December 1951). "The effect of BAL (2,3-dimercaptopropanol) on hepatolenticular degeneration (Wilson's disease)". N. Engl. J. Med. 245 (24): 917–25. doi:10.1056/NEJM195112132452401. PMID 14882450. 28. ^ Vilensky JA, Robertson WM, Gilman S (September 2002). "Denny-Brown, Wilson's disease, and BAL (British antilewisite [2,3-dimercaptopropanol])". Neurology. 59 (6): 914–6. doi:10.1212/wnl.59.6.914. PMID 12297577. 29. ^ Walshe JM (January 1956). "Wilson's disease; new oral therapy". Lancet. 270 (6906): 25–6. doi:10.1016/S0140-6736(56)91859-1. PMID 13279157. 30. ^ Walshe JM (March 1982). "Treatment of Wilson's disease with trientine (triethylene tetramine) dihydrochloride". Lancet. 1 (8273): 643–7. doi:10.1016/S0140-6736(82)92201-2. PMID 6121964. S2CID 205999334. 31. ^ Harper PL, Walshe JM (December 1986). "Reversible pancytopenia secondary to treatment with tetrathiomolybdate". Br. J. Haematol. 64 (4): 851–3. doi:10.1111/j.1365-2141.1986.tb02250.x. PMID 3801328. S2CID 11546705. 32. ^ Brewer GJ (January 2000). "Recognition, diagnosis, and management of Wilson's disease". Proc. Soc. Exp. Biol. Med. 223 (1): 39–46. doi:10.1046/j.1525-1373.2000.22305.x. PMID 10632959. Archived from the original on 2008-04-09. Retrieved 2008-05-20. 33. ^ Bull PC, Thomas GR, Rommens JM, Forbes JR, Cox DW (1993). "The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene". Nat. Genet. 5 (4): 327–37. doi:10.1038/ng1293-327. PMID 8298639. S2CID 1236890. 34. ^ Tanzi RE, Petrukhin K, Chernov I, et al. (1993). "The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene". Nat. Genet. 5 (4): 344–50. doi:10.1038/ng1293-344. PMID 8298641. S2CID 610188. 35. ^ Sternlieb I, Twedt DC, Johnson GF, et al. (1977). "Inherited copper toxicity of the liver in Bedlington terriers". Proc. R. Soc. Med. 70 Suppl 3 (Suppl 3): 8–9. PMC 1543595. PMID 122681. 36. ^ van De Sluis B, Rothuizen J, Pearson PL, van Oost BA, Wijmenga C (2002). "Identification of a new copper metabolism gene by positional cloning in a purebred dog population". Hum. Mol. Genet. 11 (2): 165–73. doi:10.1093/hmg/11.2.165. PMID 11809725. Archived from the original on 2008-08-30. Retrieved 2008-04-11. 37. ^ Müller T, van de Sluis B, Zhernakova A, et al. (2003). "The canine copper toxicosis gene MURR1 does not cause non-Wilsonian hepatic copper toxicosis". J. Hepatol. 38 (2): 164–8. doi:10.1016/S0168-8278(02)00356-2. PMID 12547404. ## External links[edit] Wikimedia Commons has media related to Wilson's disease. * Wilson's disease at Curlie * Wilson disease at NLM Genetics Home Reference Classification D * ICD-10: E83.0 * ICD-9-CM: 275.1 * OMIM: 277900 * MeSH: D006527 * DiseasesDB: 14152 External resources * MedlinePlus: 000785 * eMedicine: med/2413 neuro/570 ped/2441 * Patient UK: Wilson's disease * GeneReviews: Wilson Disease * Orphanet: 905 * v * t * e Metal deficiency and toxicity disorders Iron excess: * Iron overload * Hemochromatosis * Hemochromatosis/HFE1 * Juvenile/HFE2 * HFE3 * African iron overload/HFE4 * Aceruloplasminemia * Atransferrinemia * Hemosiderosis deficiency: * Iron deficiency Copper excess: * Copper toxicity * Wilson's disease deficiency: * Copper deficiency * Menkes disease/Occipital horn syndrome Zinc excess: * Zinc toxicity deficiency: * Acrodermatitis enteropathica Other * Inborn errors of metabolism * v * t * e Diseases of the nervous system, primarily CNS Inflammation Brain * Encephalitis * Viral encephalitis * Herpesviral encephalitis * Limbic encephalitis * Encephalitis lethargica * Cavernous sinus thrombosis * Brain abscess * Amoebic Brain and spinal cord * Encephalomyelitis * Acute disseminated * Meningitis * Meningoencephalitis Brain/ encephalopathy Degenerative Extrapyramidal and movement disorders * Basal ganglia disease * Parkinsonism * PD * Postencephalitic * NMS * PKAN * Tauopathy * PSP * Striatonigral degeneration * Hemiballismus * HD * OA * Dyskinesia * Dystonia * Status dystonicus * Spasmodic torticollis * Meige's * Blepharospasm * Athetosis * Chorea * Choreoathetosis * Myoclonus * Myoclonic epilepsy * Akathisia * Tremor * Essential tremor * Intention tremor * Restless legs * Stiff-person Dementia * Tauopathy * Alzheimer's * Early-onset * Primary progressive aphasia * Frontotemporal dementia/Frontotemporal lobar degeneration * Pick's * Dementia with Lewy bodies * Posterior cortical atrophy * Vascular dementia Mitochondrial disease * Leigh syndrome Demyelinating * Autoimmune * Inflammatory * Multiple sclerosis * For more detailed coverage, see Template:Demyelinating diseases of CNS Episodic/ paroxysmal Seizures and epilepsy * Focal * Generalised * Status epilepticus * For more detailed coverage, see Template:Epilepsy Headache * Migraine * Cluster * Tension * For more detailed coverage, see Template:Headache Cerebrovascular * TIA * Stroke * For more detailed coverage, see Template:Cerebrovascular diseases Other * Sleep disorders * For more detailed coverage, see Template:Sleep CSF * Intracranial hypertension * Hydrocephalus * Normal pressure hydrocephalus * Choroid plexus papilloma * Idiopathic intracranial hypertension * Cerebral edema * Intracranial hypotension Other * Brain herniation * Reye syndrome * Hepatic encephalopathy * Toxic encephalopathy * Hashimoto's encephalopathy Both/either Degenerative SA * Friedreich's ataxia * Ataxia–telangiectasia MND * UMN only: * Primary lateral sclerosis * Pseudobulbar palsy * Hereditary spastic paraplegia * LMN only: * Distal hereditary motor neuronopathies * Spinal muscular atrophies * SMA * SMAX1 * SMAX2 * DSMA1 * Congenital DSMA * Spinal muscular atrophy with lower extremity predominance (SMALED) * SMALED1 * SMALED2A * SMALED2B * SMA-PCH * SMA-PME * Progressive muscular atrophy * Progressive bulbar palsy * Fazio–Londe * Infantile progressive bulbar palsy * both: * Amyotrophic lateral sclerosis * v * t * e Genetic disorder, membrane: ATPase disorders ATP1 * ATP1A2 (Alternating hemiplegia of childhood) ATP2 * ATP2A1 (Brody myopathy) * ATP2A2 (Darier's disease, Acrokeratosis verruciformis) * ATP2C1 (Hailey–Hailey disease) ATP7 * ATP7A (Menkes disease) * ATP7B (Wilson's disease) ATP13 * ATP13A2 (Kufor–Rakeb syndrome) Other * Osteopetrosis B1 see also ATPase Authority control * GND: 4189925-8 * LCCN: sh85060301 * The LNB id 299223 is not valid. * NDL: 00576079 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Wilson's disease	c0019202	25,622	wikipedia	https://en.wikipedia.org/wiki/Wilson%27s_disease	2021-01-18T18:49:58	{"gard": ["7893"], "mesh": ["D006527"], "umls": ["C0019202"], "icd-9": ["275.1"], "orphanet": ["905"], "wikidata": ["Q117121"]}
Lewis-Sumner syndrome (LSS) is a rare acquired demyelinating polyneuropathy characterized by asymmetrical distal weakness of the upper or lower extremities and motor dysfunction with adult onset. It is considered to be a variant of chronic inflammatory demyelinating polyneuropathy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Lewis-Sumner syndrome	c1695985	25,623	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=48162	2021-01-23T18:22:45	{"umls": ["C1695985"], "icd-10": ["G61.8"], "synonyms": ["MADSAM", "Multifocal acquired demyelinating sensory and motor neuropathy"]}
A number sign (#) is used with this entry because of evidence that the Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome is caused by homozygous mutation in the WNT7A gene (601570) on chromosome 3p25. Description The Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome (AARRS) is a rare autosomal recessive disorder characterized by severe malformations of upper and lower limbs with severely hypoplastic pelvis and abnormal genitalia. The disorder is believed to represent a defect of dorsoventral patterning and outgrowth of limbs (summary by Kantaputra et al., 2010). Clinical Features In a daughter and son of consanguineous Jordanian parents, Al-Awadi et al. (1985) described a syndrome of severe deficiency of all 4 extremities. Both had hypoplastic femora and absent ulnae and fibulae. Although 'thoracic dystrophy,' pelvic deformity, and unusual facies were mentioned, these did not seem as impressive as the limb malformations. The authors thought this did not fit any previously described condition. Al-Awadi et al. (1985) concluded that the disorder in their patients was different from that reported by Kuhne et al. (1967); see 228200. Teebi (1993) reported that absence of the uterus was found upon reevaluation of the girl described by Al-Awadi et al. (1985). Richieri-Costa (1987) described a sporadic case of this association in a Brazilian girl. Raas-Rothschild et al. (1988) described another family, in which the 3 offspring (a boy and 2 fetuses) of double first-cousins of Oriental-Jewish ancestry were affected. One of the fetuses had occipital meningocele. The authors provided a review of autosomal recessive disorders with limb malformations. Farag et al. (1993) reported the disorder in a Bedouin infant whose parents and grandparents were consanguineous. The infant had mullerian aplasia. Intellectual development at 6 months was normal. Camera et al. (1993) described the same disorder in 2 Italian sibs who also showed very dysplastic, large ears, a high and narrow palate, and pseudarthrosis of the right clavicle. They proposed the designation Al-Awadi/Raas-Rothschild syndrome for this disorder. Schinzel (1990) described 2 female infants with phocomelia of both lower extremities with 4-toed feet. The older sister had also phocomelia of the left upper extremity and diaphragmatic hernia. The younger sister showed also a defect of the occipital bone, agenesis of the uterus and vagina, and hypoplasia of the sacrum. Chitayat et al. (1993) reported a girl of Panamanian origin with bilateral lower limb phocomelia with 3-toed feet, hypoplastic sacrum, and absence of the uterus and left ovary. The next pregnancy of the couple was terminated because of fetal acrania. Chitayat et al. (1993) noted the similarity between their patient and the patients reported by Schinzel (1990) and proposed the designation 'Schinzel-phocomelia syndrome.' Lurie and Wulfsberg (1993) showed that Al-Awadi/Raas-Rothschild syndrome and Schinzel-phocomelia syndrome are most likely different names for the same disorder, which includes skeletal defects, mullerian a- or hypoplasia, and occipital meningocele. Olney et al. (2001) reported an additional patient with Schinzel phocomelia syndrome. The infant had quadrilateral intercalary limb deficiencies, preaxial toe polydactyly, absent pelvis, large parietooccipital skull defect with no underlying brain abnormality, and extraskeletal anomalies including microtia, telecanthus, micropenis with cryptorchidism, renal cysts, stenosis of the colon, and a cleft alveolar ridge. The authors emphasized the skull and pelvis defects which assist in differentiating this condition from others with intercalary limb deficiencies. Absence of the pelvis, as was noted on prenatal ultrasound, may suggest this condition prenatally. Kantaputra and Tanpaiboon (2005) reported on a 3-year-old Thai boy with limb, pelvic, and genital malformations similar to those of AARRS. The upper limbs were more severely affected than the lower ones. Unlike the findings in AARRS, the radial ray was more severely affected than the ulnar ray. The presence of humeroulnar synostosis and humero-ulnar-radial synostosis and the absence of a radius was thought to distinguish the disorder from AARRS. The penis was unremarkable; however, there was absence of scrotum, and testes were neither palpable nor detectable by ultrasonography. Woods et al. (2006) investigated a family with 3 children diagnosed with absence of ulna and fibula with severe limb deficiency. The first child exhibited ectrodactyly of the right hand, with nail dysplasia; contractures at the right elbow joint; no left elbow joint, with the left arm ending with an appendage that looked like a deformed finger with dysplastic nail; and lower limbs replaced by a stick-like appendage (more severe on the right side). The second child had complete absence of the lower limbs, and both upper limbs lacked an elbow joint and ended with a deformed finger-like appendage with dysplastic nails. Both children had normal intelligence and health. Lonardo et al. (2007) reported 2 fetuses, born of nonconsanguineous parents, with features consistent with AARRS. Findings not previously reported included cleft palate and structural gastrointestinal abnormalities. Lonardo et al. (2007) also provided a review of the literature and proposed that diagnostic criteria for the syndrome include longitudinal/intercalary reduction of all 4 limbs, oligodactyly, and hypoplasia of the pelvis. Subhani et al. (2009) described a girl with AARRS who had pelvic, femoral, and tibial hypogenesis with absent fibula, subtle facial changes, patent foramen ovale, single umbilical artery, single kidney, imperforate anus with rectal fistula in the vaginal fourchette, and asymmetric ambiguous external genitalia. Subhani et al. (2009) suggested that AARRS, Fuhrmann syndrome (228930), and similar conditions comprise a spectrum, and that the anomaly pattern derives from serial action of the same signal pathways within primary (e.g., the major axes), secondary (e.g., heart or limb primordia), and/or local (e.g., tibial-fibular differentiation) developmental fields. Garavelli et al. (2011) suggested that Schinzel phocomelia and AARRS represent different entities because the hands and feet, as the most distal structures, are relatively unaffected in Schinzel phocomelia, whereas in AARRS the distal element is always more severely affected. However, the 2 Thai sisters described by Kantaputra et al. (2010) with mutations in the WNT7A gene presented different foot malformations: one had stick-like lower limbs as in AARRS, and the other had feet with soft dorsal parts with characteristics of soles and absent or severely hypoplastic nails as in Schinzel phocomelia. Mapping By homozygosity mapping, Woods et al. (2006) mapped the phenotype in the family they described to chromosome 3p25.1. Molecular Genetics Woods et al. (2006) considered the WNT7A gene a candidate for causative mutations in the family described by them because of its location in the linkage region and because of its known involvement in limb development. They identified a single homozygous missense mutation in exon 4, 1179C-T, that led to an R292C amino acid substitution (601570.0001). In 2 Thai sisters with short and malformed long bones, absent fibulae, flexion contracture of digits, and hypoplastic/aplastic nails, Kantaputra et al. (2010) identified homozygosity for a missense mutation in the WNT7A gene (R222W; 601570.0004). The authors noted that both sisters exhibited fusion between the severely malformed femora and slender tibiae, a feature that had not previously been reported with WNT7A mutations. In an affected brother and sister and their female cousin with variable limb reduction phenotypes, all born of consanguineous marriages within a Saudi Arabian family, Eyaid et al. (2011) identified homozygosity for a missense mutation in the WNT7A gene (G204S; 601570.0003). All 3 patients had pelvic hypoplasia and truncated appendages replacing the lower limbs, but the upper limb phenotype ranged from absence of the ulna with a short radius and 1 missing digit per hand to a single bone with absence of elbow joint and only 2 digits per hand to total absence of the upper limbs (amelia). Garavelli et al. (2011) reported a child with the AARRS phenotype who was homozygous for a mutation in the WNT7A gene (E72K; 601570.0005). INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature, disproportionate HEAD & NECK Face \- Asymmetric face \- Long face Ears \- Long ears \- Dysplastic ears \- Low-set ears Eyes \- Epicanthal folds Nose \- Broad nasal bridge Mouth \- High palate \- Narrow palate Neck \- Short neck \- Broad neck CHEST External Features \- Barrel-shaped chest Ribs Sternum Clavicles & Scapulae \- Prominent sternum \- Pectus carinatum \- Pseudoarthrosis of clavicle \- Broad clavicles \- Broad ribs Breasts \- Hypoplastic nipples GENITOURINARY External Genitalia (Male) \- Anteriorly displaced genitalia \- Hypospadias \- Hypoplastic scrotum External Genitalia (Female) \- Anteriorly displaced genitalia Internal Genitalia (Male) \- Cryptorchidism Internal Genitalia (Female) \- Absent uterus SKELETAL Skull \- Poorly ossified calvarium Spine \- Hemivertebrae Pelvis \- Hip dislocation \- Hypoplastic iliac bone \- Aplastic pubic bones Limbs \- Elbow flexion contractures \- Shortened forearm \- Short, bowed radii \- Aplastic ulnae \- Humeroradial synostosis \- Short, bowed femur \- Aplastic fibulae \- Aplastic tibiae \- Slender tibiae Hands \- Aplastic carpal bone \- Mobile wrist \- Aplastic/hypoplastic metacarpals \- Aplastic/hypoplastic phalanges \- Ectrodactyly \- Oligodactyly Feet \- Aplastic/hypoplastic tarsals \- Aplastic/hypoplastic metatarsals \- Aplastic/hypoplastic phalanges \- Hypoplastic feet \- Oligodactyly SKIN, NAILS, & HAIR Skin \- Pilonidal sinus Nails \- Anonychia NEUROLOGIC Central Nervous System \- Occipital meningocele MISCELLANEOUS \- Allelic to fibular aplasia or hypoplasia, femoral bowing, and poly-, syn-, and oligodactyly (Fuhrmann syndrome, 228930 ) MOLECULAR BASIS \- Caused by mutation in the wingless-type MMTV integration site family, member 7A gene (WNT7A, 601570.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	ULNA AND FIBULA, ABSENCE OF, WITH SEVERE LIMB DEFICIENCY	c1848651	25,624	omim	https://www.omim.org/entry/276820	2019-09-22T16:21:27	{"mesh": ["C535612"], "omim": ["276820"], "orphanet": ["2879"], "synonyms": ["LIMB/PELVIS-HYPOPLASIA/APLASIA SYNDROME", "Al Awadi-Raas-Rothschild syndrome", "Severe limb deficit", "AL-AWADI/RAAS-ROTHSCHILD SYNDROME", "Alternative titles", "Congenital absence of ulna and fibula", "SCHINZEL PHOCOMELIA SYNDROME", "Aplasia/hypoplasia of limbs and pelvis"]}
A number sign (#) is used with this entry because of evidence that sideroblastic anemia with spinocerebellar ataxia (ASAT) is caused by mutation in the ABCB7 gene (300135) on chromosome Xq13. Clinical Features Pagon et al. (1985) reported 2 apparently unrelated families with this combination and concluded that they could not distinguish between close linkage (e.g., small deletion) and pleiotropic effects of a mutant allele at a single locus. Affected males had a moderate hypochromic microcytic anemia with ring sideroblasts on bone marrow examination as in typical X-linked sideroblastic anemia (300751) but had raised, rather than normal or low, free erythrocyte protoporphyrin levels and no excessive parenchymal iron storage in adulthood. The ataxia and incoordination were evident by age 1 year, were nonprogressive, and were accompanied by long motor tract signs (hyperactive deep tendon reflexes, positive Babinski sign, clonus) in the younger affected males. Some of the obligate heterozygotes had ring sideroblasts on bone marrow examination, dimorphic peripheral blood smear, and raised free red cell protoporphyrin. The ataxia did not conform to any reported X-linked form (302500, 302600); thus, the possibility of a 'new' disorder as the pleiotropic effects of a single mutant gene. Mapping Raskind et al. (1991) showed linkage of the disorder to PGK1 (311800) with a lod score of at least 2.60 at a recombination fraction of 0. ALAS2 (301300) and ERYF1 (305371) showed no detectable alteration of restriction patterns in DNA from affected males. Raskind et al. (1991) expressed the opinion that clinically and genetically this disorder is distinct from that in previously reported families with X-linked hereditary ataxia or spastic paraparesis. Cox et al. (1992) found close linkage with no recombination between ALAS2 and DXS14, whereas Raskind et al. (1991) reported negative lod scores which excluded linkage within 5 to 10 cM of DXS14 with the sideroblastic anemia/ataxia syndrome. Molecular Genetics In a family with 5 affected males with ASAT, Allikmets et al. (1999) identified a missense mutation (I400M; 300135.0001) in the ABCB7 gene. The gene in question, an ATP-binding cassette (ABC) transporter, encodes a protein that localizes to the mitochondrial inner membrane and is involved in iron homeostasis. Thus, ASAT is a mitochondrial disease caused by a mutation in the nuclear genome. In affected members of a family with ASAT, Bekri et al. (2000) identified a missense mutation (E433K; 300135.0002) in the ABCB7 gene. INHERITANCE \- X-linked recessive NEUROLOGIC Central Nervous System \- Cerebellar ataxia, nonprogressive \- Hyperreflexia \- Extensor plantar response \- Clonus \- Dysarthria \- Dysmetria \- Intention tremor \- Dysdiadochokinesis HEMATOLOGY \- Hypochromic, microcytic anemia \- Ringed sideroblasts on bone marrow examination LABORATORY ABNORMALITIES \- Increased free erythrocyte protoporphyrin \- Lack of excessive parenchymal iron storage MISCELLANEOUS \- Onset in early childhood MOLECULAR BASIS \- Caused by mutations in the ATP-binding cassette, subfamily B, member 7 gene (ABCB7, 300135.0001 ). ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	ANEMIA, SIDEROBLASTIC, AND SPINOCEREBELLAR ATAXIA	c1845028	25,625	omim	https://www.omim.org/entry/301310	2019-09-22T16:18:47	{"doid": ["0050554"], "mesh": ["C536358"], "omim": ["301310"], "orphanet": ["2802"], "genereviews": ["NBK1321"]}
Kommerell diverticulum (KD) is a developmental anomaly of the aortic arch characterized by a diverticulum at the proximal descending aorta of left or right arch configuration that gives rise to an aberrant subclavian artery. KD is primarily asymptomatic but may become symptomatic secondary to dilatation of KD, atheroma and fibrotic changes in paratracheal or paraesophageal tissue, presenting with signs of tracheal compression (more common in children), esophageal compression (dysphagia lusoria; more common in patients with a right sided aortic arch), chest pain, or blood pressure difference in the upper limbs. KD may also predispose toward aortic dissection or rupture. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Kommerell diverticulum	c0265885	25,626	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99077	2021-01-23T18:23:27	{"umls": ["C0265885"], "icd-10": ["Q25.4"]}
Thumb deformity-alopecia-pigmentation anomaly syndrome is a rare, genetic, congenital limb malformation syndrome characterized by short stature, sparse scalp hair, hypoplastic, proximally-placed thumbs, and skin hyperpigmentation with areas of 'raindrop' depigmentation. Presence of a single, upper central incisor has also been reported. There have been no further descriptions in the literature since 1988. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Thumb deformity-alopecia-pigmentation anomaly syndrome	c2931366	25,627	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2251	2021-01-23T17:34:43	{"gard": ["5199"], "mesh": ["C536904"], "omim": ["188150"], "umls": ["C2931366"], "synonyms": ["Sparse hair-short stature-skin anomalies syndrome"]}
Osteogenesis imperfecta type IV (OI type IV) is a type of osteogenesis imperfecta, which refers to a group of conditions that affect the bones. OI type IV is the most variable form of the condition with symptoms ranging from moderately severe to so mild that it may be difficult to make the diagnosis. Although signs and symptoms can vary, affected people may experience easily broken bones, mild short stature, dentinogenesis imperfecta, adult-onset hearing loss, and normal-to-grey sclerae (the whites of the eye). OI type IV is caused by changes (mutations) in the COL1A1 or COL1A2 gene and is inherited in an autosomal dominant manner. There is currently no cure for OI type IV. Treatment is supportive and based on the signs and symptoms present in each person. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Osteogenesis imperfecta type IV	c0268363	25,628	gard	https://rarediseases.info.nih.gov/diseases/8696/osteogenesis-imperfecta-type-iv	2021-01-18T17:58:32	{"mesh": ["C536045"], "omim": ["166220"], "umls": ["C0268363"], "orphanet": ["216820"], "synonyms": ["OI type 4", "Osteogenesis imperfecta with normal sclerae", "OI type IV", "Common variable OI with normal sclerae", "Osteogenesis imperfecta type 4"]}
Trichofolliculoma SpecialtyDermatology, oncology Trichofolliculoma is a cutaneous condition characterized by a benign, highly structured tumor of the pilosebaceous unit.[1]:671[2] ## See also[edit] * Multiple familial trichoepithelioma * Pilomatricoma * Skin lesion * List of cutaneous conditions ## References[edit] 1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: Clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. 2. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 1694. ISBN 1-4160-2999-0. ## External links[edit] Classification D * ICD-10: D23 (ILDS D23.L15) * MeSH: C536553 * DiseasesDB: 31374 * SNOMED CT: 274899008 External resources * Orphanet: 864 * v * t * e Cancers of skin and associated structures Glands Sweat gland Eccrine * Papillary eccrine adenoma * Eccrine carcinoma * Eccrine nevus * Syringofibroadenoma * Spiradenoma Apocrine * Cylindroma * Dermal cylindroma * Syringocystadenoma papilliferum * Papillary hidradenoma * Hidrocystoma * Apocrine gland carcinoma * Apocrine nevus Eccrine/apocrine * Syringoma * Hidradenoma or Acrospiroma/Hidradenocarcinoma * Ceruminous adenoma Sebaceous gland * Nevus sebaceous * Muir–Torre syndrome * Sebaceous carcinoma * Sebaceous adenoma * Sebaceoma * Sebaceous nevus syndrome * Sebaceous hyperplasia * Mantleoma Hair * Pilomatricoma/Malignant pilomatricoma * Trichoepithelioma * Multiple familial trichoepithelioma * Solitary trichoepithelioma * Desmoplastic trichoepithelioma * Generalized trichoepithelioma * Trichodiscoma * Trichoblastoma * Fibrofolliculoma * Trichilemmoma * Trichilemmal carcinoma * Proliferating trichilemmal cyst * Giant solitary trichoepithelioma * Trichoadenoma * Trichofolliculoma * Dilated pore * Isthmicoma * Fibrofolliculoma * Perifollicular fibroma * Birt–Hogg–Dubé syndrome Hamartoma * Basaloid follicular hamartoma * Folliculosebaceous cystic hamartoma * Folliculosebaceous-apocrine hamartoma Nails * Neoplasms of the nailbed This Epidermal nevi, neoplasms, cysts article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Trichofolliculoma	c0334262	25,629	wikipedia	https://en.wikipedia.org/wiki/Trichofolliculoma	2021-01-18T18:45:48	{"gard": ["5263"], "mesh": ["C536553"], "umls": ["C0334262"], "icd-10": ["D23"], "orphanet": ["864"], "wikidata": ["Q2452663"]}
Some of this article's listed sources may not be reliable. Please help this article by looking for better, more reliable sources. Unreliable citations may be challenged or deleted. (June 2020) (Learn how and when to remove this template message) Driving phobia SpecialtyPsychology A driving phobia is a pathological fear of driving. It is also referred to as amaxophobia or vehophobia. Amaxophobia is an intense, persistent fear of participating in car traffic (or in other vehicular transportation) that interferes with the patient’s lifestyle and quality of life, including aspects such as inability to participate in the workforce due to the pathological and self-defeating avoidance of driving.[1][2][3] The fear of driving may be triggered by specific driving situations, such as expressway driving or dense traffic.[4] Driving anxiety can range from a mild cautious concern to an irrational phobia. ## Contents * 1 Symptoms * 1.1 Associated conditions * 2 Causes * 3 Treatment * 4 Psychological assessment * 5 See also * 6 References ## Symptoms[edit] The fear of driving is associated with various physical and subjective emotional symptoms that somewhat vary from individual to individual. For example, the physical symptoms might involve increased perspiration or tachycardia (pathologically accelerated heart rate), or hyperventilation. On the cognitive level, the patient may experience a loss of sense of reality, or thoughts of losing control while driving, even in situations that are reasonably safe.[5] On behavioral level, the avoidance of driving tends to perpetuate the phobia. Patients who developed their amaxophobia after a serious traffic accident frequently develop the post-traumatic stress disorder (PTSD) that may involve experiencing intrusive thoughts or anxious dreams of the original accident and/or other typical PTSD symptoms.[5] A noteworthy part of post-accident symptomatology is the phantom brake syndrome. It is the passenger’s partly involuntary or unintended pressing the foot on the floor of the car in a reflexive attempt "to brake." This unintended behavior usually occurs in skilled drivers when they are seated as a passenger next to a less competent person who drives the vehicle as a reflexive response to potentially dangerous traffic situations. The phantom brake syndrome is particularly common in survivors of serious car accidents.[citation needed] ### Associated conditions[edit] Some patients who present with phobia of driving also describe features consistent with various other anxiety disorders, including panic disorder, agoraphobia, specific phobia, and social phobia.[1] The majority of survivors of serious car accidents tend to experience only the phobia of driving, but they often report generalized anxiety as a part of their post-traumatic adjustment disorder.[6][unreliable source] The amaxophobia tends to be perpetuated by persistent pain caused by the car accident, and by pain related insomnia, and also by persistent post-conconcussion and whiplash symptoms caused by the accident. The PTSD symptoms, e.g., in the forms of flashbacks such as intrusive images of a bleeding person injured in the same car accident, may also contribute to amaxophobia.[citation needed] ## Causes[edit] There are three major categories of driving phobia, distinguished by their onset.[citation needed] Most common cause of a fear of driving are traffic accidents. Thus, the amaxophobia often develops as a reaction to a particularly traumatic vehicular collision. Beck and Coffey reported that 25–33% of people involved in a car collision associated with injuries and related evaluation in a hospital experience subsequent fear of driving.[5] Hickling and Blanchard[7] and Kuch, Swinson, and Kirby[8] found higher rates of driving phobia, ranging from 42% to 77%. The majority of experienced drivers with fear of driving in the aftermath of their serious accidents rate themselves as safer drivers than average, though they feel physically and emotionally too uncomfortable.[1] For some patients, the fear escalates in very specific situations such as when near large vehicles (transport trucks, buses), but in others, the fear may be triggered already just by getting seated in the car or even just by thinking about having to again travel in a car in the near future. Several psychological questionnaires have been developed for clinicians to assess the situational intensity and facets of driving anxiety in novice drivers or also in experienced drivers traumatized by a recent car accident.[9][unreliable source] Some novice drivers and passengers who were never involved in a serious car accident also report symptoms of amaxophobia.[1] The driving fear may be, in some patients, an extension of agoraphobia.[1] ## Treatment[edit] The most common treatment for both driving phobia and milder forms of driving anxiety is behavior therapy[10] in the form of systematic desensitization.[10][11][12] An emerging treatment approach to treating amaxophobia is through the use of virtual reality therapy.[13] With repeated exposure such as via devices similar to video games, the subjective distress is gradually reduced: the patient may subsequently be more willing to proceed to engaging in driving in real life situations, as the next stage of exposure therapy.[citation needed] ## Psychological assessment[edit] This section has multiple issues. 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(June 2020) (Learn how and when to remove this template message) (Learn how and when to remove this template message) Driving is a potentially dangerous activity. Almost every driver experiences some driving anxiety, in some situations, especially new drivers. Psychological assessment of novice drivers can proceed via questionnaires such as the Driving Behavior Survey (DBS)[14] which consists of 20 items, each of which is rated on a scale from 1=never to 7=always, for example Item 4. "I have trouble staying in the correct lane," 5. "I drift into other lanes," 6. "I forget to make appropriate adjustments in speed." Lack of experience with driving or lack of driving skills in novice drivers obviously constitutes a different source of anxiety than the sudden traumatic event that generated post-accident anxiety of drivers who were adequately self-confident in cars until the collision. Another assessment tool designed for phobic fear in novice drivers is the Driving Cognition Questionnaire (DCQ).[15] It also consists of 20 items. These are rated on a scale from 0=never to 4=always. Some items of this questionnaire assess related social anxieties and self-image issues, e.g., Item 8. "People will think I am a bad driver," 15. "I will hold up traffic and people will be angry," 17. "People will laugh at me," and 20. "I will lose control of myself and act stupidly or dangerously." Such self-image issues are relatively uncommon in patients with a post-accident amaxophobia some of whom drove without accidents and without emotional discomfort for decades. The Driving and Riding Avoidance Scale (DRAS)[16] also consists of 20 items. These are scored from 0="rarely or none of the time" to 4="Most or all of the time." Its 20 items describe various situations in which driving is avoided. As discussed by Taylor and Sullman,[17] the wording of DRAS items allows for responses that are not necessarily based on fear of driving, but could also involve economic or practical issues. For instance, the travel via subway trains or streetcars within the center of some major North American or European cities is far more rapid than in cars and/or it saves both gasoline and parking fees. Canadian psychotherapist James Whetstone has developed his Vehicle Anxiety Questionnaire to assess the driving phobia of survivors of car accidents.[9] Whetstone’s questionnaire is particularly suited for assessments of experienced but traumatized drivers and maps the driving phobia along 6 dimensions: (1) Compensating driving behaviours (Items 1 to 6), (2) Passenger anxieties (Items 7 to 10), (3) Physical manifestations of anxiety (Items 11 to 16), (4) Limitations to mobility (Items 17 to 21), (5) Avoidance behaviours (Items 22 to 26), and (6) Challenges to personal and relationship stability (Items 27 to 31). The answers to Whetstone items can be scored with 0 points for "Not at All," 1 for "Mildly," 2 for "Frequently," and with 3 points for "Constantly." In clinical use, as the last part of Whetstone questionnaire, the patients are also asked to provide ratings, on a scale from 1 to 10, of anxiety as a driver or as a passenger since their accident and then, also separately the rating of their driver and passenger anxiety over the years before the accident. In the criterion validation study, responses to Whetstone’s questionnaire of 53 survivors of car accidents were compared to those of 24 normal controls. There was no overlap between the score distribution in the group of patients (lowest score was 23) and the control group (highest score was 19). The patients’ scores ranged from 23 to 93, with the average at 65.5 (SD=17.4) and those in a control group ranged from 0 to 19, with the average at 6.8 (SD=5.1). The convergent validity was also very satisfactory: high correlations were found of Whetstone questionnaire to the Driving Anxiety Questionnaire (r=.80) and to the PCL-5 measure of PTSD symptoms (r=.78). Whetstone scores were found to be also highly correlated with the post-concussion syndrome (r=.63) and moderately with whiplash symptoms (r=.46), post-accident insomnia (r=.56), ratings of post-accident pain (rs ranging from .43 to .50), and ratings of depression (r=.40) and of generalized anxiety (r=.43). Significant correlation was also found of Whetstone to Steiner’s Automobile Anxiety Inventory (r=.45). Whetstone’s article also provides the full text of the Driving Anxiety Questionnaire (DAQ) that consists of a list of driving situations that are rated by the patient on a scale from "No Anxiety" to "Severe Anxiety." This list consists of 14 situational items which the patient at first rates as a driver and then again separately as a passenger. The DAQ also includes 6 items describing behaviors indicative of anxiety as a driver and 7 items as a passenger. The study by Whetstone et al. reported also psychometric findings on the DAQ: its coefficients of convergent validity were satisfactory. The DAQ is especially well suited for behavior therapists for designing an individualized exposure therapy for each particular patient. A noteworthy part of this questionnaire is its measure of the phantom brake syndrome (the passenger’s partly involuntary or unintended pressing the foot on the floor of the car in a reflexive attempt "to brake"; this reaction is common in skilled drivers who survived car accidents when travelling in the passenger seat).[9] The article by Whetstone et al. also reviews the Automobile Anxiety Inventory (AAI) developed in Ontario by Leon Steiner.[18][unreliable source] Steiner’s AAI is a 23 item questionnaire of which 18 such are scored on a dichotomous basis (1=Yes, 0=No). Its convergent validity is adequate.[18] Most of the AAI items compare the level of driving anxiety before the accident to the one after the accident. The AAI is written in relatively simple English. Steiner’s AAI questionnaire is especially well suited for patients who read rarely or only reluctantly or for those with only elementary knowledge of written English. Since each of these 3 questionnaires (i.e., Whetstone's, Steiner's, and the DAQ) has a slightly different focus, it is often of advantage to use all 3 jointly in clinical assessments, as long as enough time is available.[citation needed] Another psychological evaluation tool is the Gutierrez questionnaire developed by Jaime Gutierrez for assessments of patients after car accidents.[6] A multifaceted assessment of driving anxiety is accomplished by using separately the items 54 to 65 of the Gutierrez questionnaire. Its items evaluate physical reactions, since accident, while again in cars, related feelings, behaviors such as avoidance of car trips or the phantom brake syndrome of drivers when travelling as a passenger (reflexive pressing the foot on the floor in situations subjectively perceived as potentially dangerous). The Gutierrez questionnaire also includes items listing various driving situations: the patient is to check those associated with anxiety. This provides useful data for systematic desensitization therapy[10] of driving anxiety. ## See also[edit] * Psychology portal * List of phobias ## References[edit] 1. ^ a b c d e Taylor, Joanne E.; Deane, Frank P.; Podd, John V. (September–October 2000). "Determining the focus of driving fears". Journal of Anxiety Disorders. 14 (5): 453–470. doi:10.1016/s0887-6185(00)00033-5. PMID 11095540. 2. ^ Taylor, Joanne; Deane, Frank; Podd, John (June 2002). "Driving-related Fear: A Review". Clinical Psychology Review. 22 (5): 631–645. doi:10.1016/s0272-7358(01)00114-3. PMID 12113199. 3. ^ Taylor, Joanne E. (2002). Understanding Driving-Related Fear (PhD thesis). Massey University. 4. ^ Mathew, R. J.; Weinman, M. L.; Semchuk, K. M.; Levin, B. L. (August 1982). "Driving phobia in the city of Houston: a pilot study". American Journal of Psychiatry. 139 (8): 1049–1051. doi:10.1176/ajp.139.8.1049. PMID 7091430. 5. ^ a b c Beck, J. Gayle; Coffey, Scott F. (December 2007). "Assessment and treatment of PTSD after a motor vehicle collision: Empirical findings and clinical observations". Professional Psychology: Research and Practice. 38 (6): 629–639. doi:10.1037/0735-7028.38.6.629. PMC 2396820. PMID 18509507. 6. ^ a b Gutierrez, Jaime; Nosonova, Vitalina; Cernovsky, Zack; Fattahi, Milad; Tenenbaum, Silvia (2019). "Gutierrez Questionnaire for Assessments of Patients after Car Accidents" (PDF). Archives of Psychiatry and Behavioral Sciences. 2 (2): 10–21. ISSN 2638-5201. Archived (PDF) from the original on June 19, 2020. 7. ^ Hickling, Edward J.; Blanchard, Edward B. (July–September 1992). "Post-traumatic stress disorder and motor vehicle accidents". Journal of Anxiety Disorders. 6 (3): 285–291. doi:10.1016/0887-6185(92)90040-E. 8. ^ Kuch, Klaus; Swinson, Richard P.; Kirby, Marlene (October 1985). "Post-traumatic Stress Disorder After Car Accidents". The Canadian Journal of Psychiatry. 30 (6): 426–427. doi:10.1177/070674378503000610. PMID 4063939. S2CID 6092875. 9. ^ a b c Whetstone, James Paul; et al. (2020). "Validation of James Whetstone's Measure of Amaxophobia" (PDF). Archives of Psychiatry and Behavioral Sciences. 3 (1): 23–33. ISSN 2638-5201. Archived (PDF) from the original on June 19, 2020. 10. ^ a b c Wolpe, Joseph (1968). "Psychotherapy by Reciprocal Inhibition". Conditional Reflex. Stanford University Press. 3 (4): 234–40. doi:10.1007/BF03000093 (inactive 2021-01-14). ISBN 978-0804705097. LCCN 58006709. PMID 5712667.CS1 maint: DOI inactive as of January 2021 (link) 11. ^ Rachman, S. (1967). "Systematic desensitization". Psychological Bulletin. 67 (2): 93–103. doi:10.1037/h0024212. PMID 6045340. 12. ^ Lauer, G. (1992). "The Treatment of Driving Phobia". International Journal of Psychology. 27 (3–4): 469. doi:10.1080/00207599208246897. 13. ^ Walshe, David G.; Lewis, Elizabeth J.; Kim, Sun I.; O'Sullivan, Kathleen; Wiederhold, Brenda K. (June 2003). "Exploring the Use of Computer Games and Virtual Reality in Exposure Therapy for Fear of Driving Following a Motor Vehicle Accident" (PDF). CyberPsychology & Behavior. 6 (3): 329–234. doi:10.1089/109493103322011641. PMID 12855091. Archived (PDF) from the original on June 19, 2020. 14. ^ Clapp, Joshua D.; et al. (January 2011). "The Driving Behavior Survey: Scale construction and validation". Journal of Anxiety Disorders. 25 (1): 96–105. doi:10.1016/j.janxdis.2010.08.008. PMC 3006470. PMID 20832988. 15. ^ Ehlers, Anke; et al. (2007). "The Driving Cognitions Questionnaire: Development and preliminary psychometric properties". Journal of Anxiety Disorders. 21 (4): 493–509. doi:10.1016/j.janxdis.2006.08.002. PMID 16982173. 16. ^ Stewart, Alan E.; St. Peter, Claire C. (August 2004). "Driving and riding avoidance following motor vehicle crashes in a non-clinical sample: psychometric properties of a new measure". Behaviour Research and Therapy. 42 (8): 859–879. doi:10.1016/S0005-7967(03)00203-1. PMID 15178463. 17. ^ Taylor, Joanne E.; Sullman, Mark J. M. (May 2009). "What does the Driving and Riding Avoidance Scale (DRAS) measure?". Journal of Anxiety Disorders. 23 (3): 504–510. doi:10.1016/j.janxdis.2008.10.006. PMID 19062251. 18. ^ a b Steiner, Leon; Cernovsky, Zack (2020). "Convergent Validity of Leon Steiner's Measure of Driving Phobia" (PDF). Archives of Psychiatry and Behavioral Sciences. 3 (1): 45–50. ISSN 2638-5201. Archived (PDF) from the original on June 19, 2020. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Driving phobia	c1112258	25,630	wikipedia	https://en.wikipedia.org/wiki/Driving_phobia	2021-01-18T18:46:58	{"wikidata": ["Q5308134"]}
Autosomal systemic lupus erythematosus is a rare, genetic, multisystemic, chronic autoimmune disease characterized by the presence of systemic lupus erythematosus symptoms in two or more members of a single family. Patients present a wide spectrum of clinical manifestations, including cutaneous (malar rash, photosensitivity), ocular (keratoconjunctivitis sicca, retinopathy), gastrointestinal (oral ulceration, abdominal pain), cardiac (atherosclerosis, chest pain), pulmonary (serositis, pleurisy), musculoskeletal (arthralgia, myalgia), renal (nephritis, hematuria), obstetrical (increased spontaneous abortions, neonatal lupus), constitutional (fatigue, loss of appetite) and neuropsychiatric (mood and cognitive disorders) involvement, among others. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Autosomal systemic lupus erythematosus	c3280742	25,631	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=300345	2021-01-23T18:42:18	{"omim": ["614420"], "icd-10": ["M32.8"], "synonyms": ["Autosomal SLE", "Familial SLE", "Familial systemic lupus erythematosus"]}
A rare ciliopathy characterized by profound congenital deafness, retinitis pigmentosa and vestibular dysfunction. Retinitis pigmentosa results in visual loss and generally manifests as night blindness, progressively constricted visual fields, and impaired visual acuity. Vestibular dysfunction a defining feature of this form, manifests as delayed motor development with affected infants taking longer to sit independently and to walk. Later on, vestibular dysfunction results in difficulty with activities requiring balance. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Usher syndrome type 1	c1848638	25,632	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=231169	2021-01-23T17:37:52	{"gard": ["5435"], "mesh": ["C564755"], "omim": ["276900", "276904", "601067", "602083", "602097", "606943", "612632", "614869", "614990", "618632"], "umls": ["C0339533"], "icd-10": ["H35.5"], "synonyms": ["USH1"]}
Borderline epithelial tumor of the ovary is an uncommon epithelial ovarian neoplasm, distinguished from ovarian carcinomas by the absence of destructive stromal invasion, generally characterized by indolent behavior and excellent prognosis. Most patients are asymptomatic at the time of diagnosis, and the symptoms, if present, are often nonspecific and vague, such as pelvic pain, abdominal mass or, rarely, gastrointestinal problems including early satiety or bloating. Six histological subtypes are currently recognized, based on the epithelial cell type. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Borderline epithelial tumor of ovary	c3665489	25,633	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=206473	2021-01-23T18:43:54	{"umls": ["C3665489"], "icd-10": ["C56"], "synonyms": ["Borderline ovarian epithelial tumor", "Ovarian tumor of low malignant potential"]}
Primary lymphedema is a lymphatic system malformation characterized by swelling of an extremity that can be associated with other lymphatic effusions, due to an underlying developmental anomaly of the lymphatic system (abnormal lymphoangiogenesis). It can be hereditary or not and be congenital or late onset. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Primary lymphedema	c1704423	25,634	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=77240	2021-01-23T16:57:36	{"mesh": ["D008209"], "icd-10": ["I89.0"]}
Human immunodeficiency virus salivary gland disease (abbreviated to HIV-SGD,[1] and also termed HIV-associated salivary gland disease),[2] is swelling of the salivary glands and/or xerostomia in individuals infected with human immunodeficiency virus. ## Contents * 1 Signs and symptoms * 2 Epidemiology * 3 References ## Signs and symptoms[edit] * Gradual enlargement of the major salivary glands, particularly the parotid glands.[3] This swelling may be on one side or both sides, may cause disfigurement and may be painful.[2] * Xerostomia (dry mouth) with no other cause such as a side effect of medications.[2] HIV-SGD may be the presenting sign of HIV infection.[3] There may also be xerophthalmia (dry eyes) and arthralgia (joint pain), similar to Sjögren syndrome.[3] ## Epidemiology[edit] HIV-SGD is more prevalent in HIV positive children than HIV positive adults,[4] at about 19% and 1% respectively.[1] Unlike other oral manifestations of HIV/AIDS such as Kaposi sarcoma, oral hairy leukoplakia and oral candidiasis, which decreased following the introduction of highly active antiretroviral therapy (HAART), HIV-SGD has increased.[2] ## References[edit] 1. ^ a b Burket LW; Greenberg MS; Michael Glick; Jonathan A. Ship (2008). Burket's Oral Medicine. PMPH-USA. pp. 207–208. ISBN 978-1-55009-345-2. 2. ^ a b c d Jeffers, L; Webster-Cyriaque, JY (April 2011). "Viruses and salivary gland disease (SGD): lessons from HIV SGD". Advances in Dental Research. 23 (1): 79–83. doi:10.1177/0022034510396882. PMC 3144046. PMID 21441486. 3. ^ a b c Witt RL (1 January 2011). Salivary Gland Diseases: Surgical and Medical Management. Thieme. pp. 60–61. ISBN 978-1-60406-537-4. 4. ^ Schiødt, M (February 1992). "HIV-associated salivary gland disease: a review". Oral Surgery, Oral Medicine, and Oral Pathology. 73 (2): 164–7. doi:10.1016/0030-4220(92)90189-w. PMID 1549310. * v * t * e Oral and maxillofacial pathology Lips * Cheilitis * Actinic * Angular * Plasma cell * Cleft lip * Congenital lip pit * Eclabium * Herpes labialis * Macrocheilia * Microcheilia * Nasolabial cyst * Sun poisoning * Trumpeter's wart Tongue * Ankyloglossia * Black hairy tongue * Caviar tongue * Crenated tongue * Cunnilingus tongue * Fissured tongue * Foliate papillitis * Glossitis * Geographic tongue * Median rhomboid glossitis * Transient lingual papillitis * Glossoptosis * Hypoglossia * Lingual thyroid * Macroglossia * Microglossia * Rhabdomyoma Palate * Bednar's aphthae * Cleft palate * High-arched palate * Palatal cysts of the newborn * Inflammatory papillary hyperplasia * Stomatitis nicotina * Torus palatinus Oral mucosa – Lining of mouth * Amalgam tattoo * Angina bullosa haemorrhagica * Behçet's disease * Bohn's nodules * Burning mouth syndrome * Candidiasis * Condyloma acuminatum * Darier's disease * Epulis fissuratum * Erythema multiforme * Erythroplakia * Fibroma * Giant-cell * Focal epithelial hyperplasia * Fordyce spots * Hairy leukoplakia * Hand, foot and mouth disease * Hereditary benign intraepithelial dyskeratosis * Herpangina * Herpes zoster * Intraoral dental sinus * Leukoedema * Leukoplakia * Lichen planus * Linea alba * Lupus erythematosus * Melanocytic nevus * Melanocytic oral lesion * Molluscum contagiosum * Morsicatio buccarum * Oral cancer * Benign: Squamous cell papilloma * Keratoacanthoma * Malignant: Adenosquamous carcinoma * Basaloid squamous carcinoma * Mucosal melanoma * Spindle cell carcinoma * Squamous cell carcinoma * Verrucous carcinoma * Oral florid papillomatosis * Oral melanosis * Smoker's melanosis * Pemphigoid * Benign mucous membrane * Pemphigus * Plasmoacanthoma * Stomatitis * Aphthous * Denture-related * Herpetic * Smokeless tobacco keratosis * Submucous fibrosis * Ulceration * Riga–Fede disease * Verruca vulgaris * Verruciform xanthoma * White sponge nevus Teeth (pulp, dentin, enamel) * Amelogenesis imperfecta * Ankylosis * Anodontia * Caries * Early childhood caries * Concrescence * Failure of eruption of teeth * Dens evaginatus * Talon cusp * Dentin dysplasia * Dentin hypersensitivity * Dentinogenesis imperfecta * Dilaceration * Discoloration * Ectopic enamel * Enamel hypocalcification * Enamel hypoplasia * Turner's hypoplasia * Enamel pearl * Fluorosis * Fusion * Gemination * Hyperdontia * Hypodontia * Maxillary lateral incisor agenesis * Impaction * Wisdom tooth impaction * Macrodontia * Meth mouth * Microdontia * Odontogenic tumors * Keratocystic odontogenic tumour * Odontoma * Dens in dente * Open contact * Premature eruption * Neonatal teeth * Pulp calcification * Pulp stone * Pulp canal obliteration * Pulp necrosis * Pulp polyp * Pulpitis * Regional odontodysplasia * Resorption * Shovel-shaped incisors * Supernumerary root * Taurodontism * Trauma * Avulsion * Cracked tooth syndrome * Vertical root fracture * Occlusal * Tooth loss * Edentulism * Tooth wear * Abrasion * Abfraction * Acid erosion * Attrition Periodontium (gingiva, periodontal ligament, cementum, alveolus) – Gums and tooth-supporting structures * Cementicle * Cementoblastoma * Gigantiform * Cementoma * Eruption cyst * Epulis * Pyogenic granuloma * Congenital epulis * Gingival enlargement * Gingival cyst of the adult * Gingival cyst of the newborn * Gingivitis * Desquamative * Granulomatous * Plasma cell * Hereditary gingival fibromatosis * Hypercementosis * Hypocementosis * Linear gingival erythema * Necrotizing periodontal diseases * Acute necrotizing ulcerative gingivitis * Pericoronitis * Peri-implantitis * Periodontal abscess * Periodontal trauma * Periodontitis * Aggressive * As a manifestation of systemic disease * Chronic * Perio-endo lesion * Teething Periapical, mandibular and maxillary hard tissues – Bones of jaws * Agnathia * Alveolar osteitis * Buccal exostosis * Cherubism * Idiopathic osteosclerosis * Mandibular fracture * Microgenia * Micrognathia * Intraosseous cysts * Odontogenic: periapical * Dentigerous * Buccal bifurcation * Lateral periodontal * Globulomaxillary * Calcifying odontogenic * Glandular odontogenic * Non-odontogenic: Nasopalatine duct * Median mandibular * Median palatal * Traumatic bone * Osteoma * Osteomyelitis * Osteonecrosis * Bisphosphonate-associated * Neuralgia-inducing cavitational osteonecrosis * Osteoradionecrosis * Osteoporotic bone marrow defect * Paget's disease of bone * Periapical abscess * Phoenix abscess * Periapical periodontitis * Stafne defect * Torus mandibularis Temporomandibular joints, muscles of mastication and malocclusions – Jaw joints, chewing muscles and bite abnormalities * Bruxism * Condylar resorption * Mandibular dislocation * Malocclusion * Crossbite * Open bite * Overbite * Overeruption * Overjet * Prognathia * Retrognathia * Scissor bite * Maxillary hypoplasia * Temporomandibular joint dysfunction Salivary glands * Benign lymphoepithelial lesion * Ectopic salivary gland tissue * Frey's syndrome * HIV salivary gland disease * Necrotizing sialometaplasia * Mucocele * Ranula * Pneumoparotitis * Salivary duct stricture * Salivary gland aplasia * Salivary gland atresia * Salivary gland diverticulum * Salivary gland fistula * Salivary gland hyperplasia * Salivary gland hypoplasia * Salivary gland neoplasms * Benign: Basal cell adenoma * Canalicular adenoma * Ductal papilloma * Monomorphic adenoma * Myoepithelioma * Oncocytoma * Papillary cystadenoma lymphomatosum * Pleomorphic adenoma * Sebaceous adenoma * Malignant: Acinic cell carcinoma * Adenocarcinoma * Adenoid cystic carcinoma * Carcinoma ex pleomorphic adenoma * Lymphoma * Mucoepidermoid carcinoma * Sclerosing polycystic adenosis * Sialadenitis * Parotitis * Chronic sclerosing sialadenitis * Sialectasis * Sialocele * Sialodochitis * Sialosis * Sialolithiasis * Sjögren's syndrome Orofacial soft tissues – Soft tissues around the mouth * Actinomycosis * Angioedema * Basal cell carcinoma * Cutaneous sinus of dental origin * Cystic hygroma * Gnathophyma * Ludwig's angina * Macrostomia * Melkersson–Rosenthal syndrome * Microstomia * Noma * Oral Crohn's disease * Orofacial granulomatosis * Perioral dermatitis * Pyostomatitis vegetans Other * Eagle syndrome * Hemifacial hypertrophy * Facial hemiatrophy * Oral manifestations of systemic disease [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	HIV salivary gland disease	None	25,635	wikipedia	https://en.wikipedia.org/wiki/HIV_salivary_gland_disease	2021-01-18T18:42:05	{"wikidata": ["Q25339379"]}
A number sign (#) is used with this entry because of evidence that susceptibility to obesity can be conferred by heterozygous mutation in the MC3R gene (155540) on chromosome 20q13. For a phenotypic description and a discussion of genetic heterogeneity of body mass index (BMI), see 606641. Mapping Lembertas et al. (1997) identified a quantitative trait locus for obesity on distal mouse chromosome 2 by analysis of NZB/BINJ x SM/J intercross mice. This region of the mouse genome, syntenic with a large region of human chromosome 20, showed linkage to percent body fat and fat mass. The QTL was confirmed in a congenic mouse strain. To test whether the QTL contributes to human obesity (see 601665), Lembertas et al. (1997) studied linkage between markers located within a 52-cM region extending from 20p12 to 20q13.3 and measures of obesity in 650 French-Canadian subjects from 152 pedigrees participating in the Quebec Family Study. Sib-pair analyses based on a maximum of 258 sib pairs showed suggestive linkage between the percentage of body fat, body mass index, and fasting insulin and a locus extending approximately from ADA (608958) to MC3R (155540). These genes are located at 20q13.2 and 20q13.11, respectively. Lembertas et al. (1997) concluded that a locus on 20q contributes to body fat and also to fasting insulin levels in a human population. The authors also demonstrated the usefulness of interspecies syntenic relationships to find relevant disease loci in humans. Lee et al. (1999) likewise found evidence for linkage to 20q13 in a genome screen based on 354 markers in 513 members of 92 nuclear families ascertained through extreme obesity. After finding preliminary evidence of linkage, they studied an augmented sample of 713 members from 124 families. They commented that the plausible candidate genes for obesity that map to the 20q11-q13 region include agouti signaling protein (ASIP; 600201) and CCAAT/enhancer-binding protein-beta (CEBPB; 189965), which has a role in adipocyte differentiation. Hunt et al. (2001) analyzed 48 genetic markers on chromosome 20 for linkage to severe obesity (body mass index 35 or more) in 103 extended Utah pedigrees (1,711 individuals), all of which had strong aggregation of severe obesity. A simple dominant model produced a maximum multipoint heterogeneity lod score of 3.5 at D20S438 (55.1 cM). A 1-gene/2-mutation model (with 1 dominant mutation and 1 recessive mutation) increased the lod score to 4.2. A 2-locus model (with 1 locus dominant and 1 recessive) generated a multipoint lod score of 4.9. Hunt et al. (2001) concluded that 1 or more severe obesity- predisposing genes lie within an interval of approximately 10 cM on chromosome 20. The analysis suggested that the predisposing genes are localized very near the centromere of chromosome 20. Dong et al. (2003) presented results from multiple methods and correlated phenotypes consistent with the suggestion that epistatic interactions between loci on chromosomes 20q (65-83 cM) and 10q (88-97 cM) play a role in extreme human obesity. See 607514 for a discussion of the locus on 10q. Molecular Genetics In a 13-year-old obese girl and her father, Lee et al. (2002) identified a heterozygous mutation (I183N; 155540.0001) in the MC3R gene. Functional characterization of the I183N mutant by Tao and Segaloff (2004) demonstrated a complete lack of signaling in response to agonist stimulation. Feng et al. (2005) analyzed the MC3R gene in 190 overweight and 160 nonoverweight children and found that 29 (8.2%) children were double homozygous for 2 missense variants, T6L and V81I. The double homozygous children were significantly heavier (p less than 0.0001), had more body fat (p less than 0.001), and had greater plasma leptin (p less than 0.0001) and insulin concentrations (p less than 0.001) and greater insulin resistance (p less than 0.008) than wildtype or heterozygous children. Both sequence variants were more common in African American than in Caucasian children. Mencarelli et al. (2008) sequenced the MC3R gene in 290 obese individuals and 215 normal-weight controls and identified 3 heterozygous mutations present in 3 obese individuals, respectively, that were not present in controls. Although there were only a limited number of family members available for study, there appeared to be cosegregation of the mutations with the obese phenotype. In vitro functional studies of 1 of the mutations (I335S; 155540.0002) showed intracellular retention and complete loss of function of the mutant receptor. Calton et al. (2009) studied MC3R variants detected in a total of 1,821 North American adults (889 severely obese and 932 lean controls) from 2 cohorts, and did not find an association between variants in the MC3R gene and severe obesity in this population. Mencarelli et al. (2011) evaluated the entire coding region of MC3R in 839 severely obese individuals and 967 lean controls of French or Italian origin and performed in vitro functional analysis of the detected mutations. The total prevalence of rare MC3R variants was not significantly different in obese individuals compared to controls (p = 0.18). However, the prevalence of mutations associated with reduced MC3R signaling was significantly higher in the obese group (p = 0.22), suggesting that impairment of MC3R signaling is associated with obesity. History One method for identifying genetic loci that contribute to complex traits in animals is quantitative trait locus (QTL) mapping, which involves interbreeding 2 strains of mice that differ in the phenotype of interest for 2 generations to produce F2 mice. Each of these F2 mice represents a genetically unique combination of parental genes and phenotypes. The genome is then tested for the parental origin of the genetic elements, using polymorphic genetic markers in a genomewide scan. Finally, statistical association of the inheritance of particular parental traits with unique genetic elements identifies loci that contain genes affecting these traits. Lembertas et al. (1997) noted that these 'loci' are broad, encompassing distances of 15 to 30 cM. Resolution is limited by the number of genetic recombinations represented in the population examined, and, unlike simple mendelian traits, a multigenic phenotype may require the coinheritance of minor genetic elements for the effect of the major locus to be seen. A genetic locus can also be isolated from other genes controlling the trait by incorporating a small chromosomal segment containing the gene of interest from 1 mouse strain onto the genome of a second mouse strain by selective breeding to create a congenic strain, using methods that were developed by George Snell (1948) of The Jackson Laboratory for the study of histocompatibility genes. The method allows comparison of a phenotype of a congenic strain with the phenotype of its background strain and identification of effects of single genes derived from the donor strain. Growth \- Body fat content Lab \- Fasting insulin levels Inheritance \- Broad locus on 20q ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	BODY MASS INDEX QUANTITATIVE TRAIT LOCUS 9	c2677162	25,636	omim	https://www.omim.org/entry/602025	2019-09-22T16:14:06	{"omim": ["602025"], "synonyms": ["Alternative titles", "OBESITY, SUSCEPTIBILITY TO"]}
A number sign (#) is used with this entry because of evidence that mitochondrial DNA depletion syndrome-16 (MTDPS16) is caused by homozygous mutation in the POLG2 gene (604983) on chromosome 17q23. One such patient has been reported. For a discussion of genetic heterogeneity of autosomal recessive mtDNA depletion syndromes, see MTDPS1 (603041). Clinical Features Varma et al. (2016) reported a 3-month-old boy with fulminant neonatal hepatic failure resulting in death at 9 months of age (Hoff et al., 2018). The patient presented with poor feeding, difficulty breathing, and abdominal distention. Laboratory studies showed profound metabolic acidosis, increased lactate, hyperkalemia, elevated liver enzymes, elevated total bilirubin and bile acids, decreased albumin, and coagulopathy. He also an abnormal carnitine profile, suggesting mitochondrial dysfunction. Liver biopsy showed microvesicular steatosis, cholestasis, and panlobular fibrosis, as well as abnormally shaped mitochondria. Severe mtDNA depletion was seen in the liver (25% of control levels), muscle (20%), and blood leukocytes (44%). Muscle biopsy was essentially normal aside from mtDNA depletion and mild ultrastructural alterations in mitochondria. Neurologic examination was unremarkable and muscle tone was normal; brain imaging showed thin corpus callosum. Family history revealed that the mother of the proband had 2 early first trimester miscarriages and a stillbirth at 8 months. Inheritance The transmission pattern of MTDPS16 in the family reported by Varma et al. (2016) was consistent with autosomal recessive inheritance. Molecular Genetics In a male infant with MTDPS16, Varma et al. (2016) identified a homozygous c.544C-T transition in the POLG2 gene, resulting in an arg182-to-trp (R182W) substitution (R182W; 604983.0006) at a residue in the dimerization base that is conserved in vertebrates. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was found in the heterozygous state in each unaffected parent, confirming segregation. The variant was not found in the 1000 Genomes Project, Exome Variant Server, or ExAC databases. Functional studies of the variant were not performed, but it was predicted to disrupt POLG2 homodimerization and cause loss of progressive mtDNA synthesis. Patient tissues showed variable degrees of mtDNA depletion. Hoff et al. (2018) performed functional studies on the R182W variant. Patient-derived fibroblasts showed a growth defect associated with reduced mtDNA copy number and decreased mRNA levels of both POLG (174763) and POLG2 compared to controls. HEK293 cells transfected with the mutation showed defective oxidative phosphorylation, impaired respiratory activity, and decreased ATP production. The R182W protein showed similar DNA-binding abilities and association with POLG as wildtype POLG2. However, the mutant protein showed reduced thermostability, suggesting structural instability, and impaired ability to stimulate POLG compared to wildtype. INHERITANCE \- Autosomal recessive ABDOMEN External Features \- Abdominal distention Liver \- Hepatic failure \- Hepatomegaly \- Microvesicular steatosis seen on liver biopsy \- Panlobular fibrosis \- Cholestasis \- Abnormal mitochondrial morphology Gastrointestinal \- Poor feeding SKIN, NAILS, & HAIR Skin \- Jaundice NEUROLOGIC Central Nervous System \- Thin corpus callosum METABOLIC FEATURES \- Metabolic acidosis HEMATOLOGY \- Coagulation defects secondary to liver dysfunction LABORATORY ABNORMALITIES \- Abnormal liver enzymes \- Increased bilirubin \- Increased bile acids \- Increased serum lactate \- Decreased albumin \- Abnormal carnitine profile \- Depletion of mtDNA in various tissues MISCELLANEOUS \- Onset in the neonatal period \- Death in infancy \- One patient has been reported (last curated August 2019) MOLECULAR BASIS \- Caused by mutation in the polymerase, DNA, gamma-2 gene (POLG2, 604983.0006 ) ▲ 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-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	MITOCHONDRIAL DNA DEPLETION SYNDROME 16 (HEPATIC TYPE)	None	25,637	omim	https://www.omim.org/entry/618528	2019-09-22T15:41:34	{"omim": ["618528"]}
Distal myopathy with anterior tibial onset is a rare, genetic neuromuscular disease characterized by a progressive muscle weakness starting in the anterior tibial muscles, later involving lower and upper limb muscles, associated with an increased serum creatine kinase levels and absence of dysferlin on muscle biopsy. Patients become wheelchair dependent. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Distal myopathy with anterior tibial onset	c1847532	25,638	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=178400	2021-01-23T18:19:43	{"mesh": ["C564664"], "omim": ["606768"], "umls": ["C1847532"], "icd-10": ["G71.0"], "synonyms": ["Distal anterior compartment myopathy"]}
A heterogeneous group of diseases characterized by fragility of the soft connective tissues resulting in widespread skin, ligament, joint, blood vessel and/or internal organ manifestations. Clinical spectrum is highly variable, ranging from mild skin and joint hyperlaxity to severe physical disability and life-threatening vascular complications. Overlap with osteogenesis imperfecta may be observed resulting in an EDS/osteogenesis imperfecta overlap phenotype. Diseases in this group include classical Ehlers-Danlos syndrome (EDS), musculocontractural EDS, hypermobile EDS, vascular EDS, arthrochalasia EDS, dermatosparaxis EDS, periodontal EDS, X-linked EDS, brittle cornea syndrome, classical-like EDS type 1 and type 2, cardiac-valvular EDS, spondylodysplastic EDS, myopathic EDS, and kyphoscoliotic EDS. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Ehlers-Danlos syndrome	c0013720	25,639	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98249	2021-01-23T18:53:58	{"gard": ["6322"], "mesh": ["D004535"], "umls": ["C0013720"], "icd-10": ["Q79.6"]}
"Duplicate vagina" redirects here. For the two lateral vaginas which are normally present in female marsupials, see Marsupial female reproductive system. Vaginal septum SpecialtyGynecology A vaginal septum is a vaginal anomaly that is partition within the vagina; such a septum could be either longitudinal or transverse. In some affected women, the septum is partial or does not extend the length or width of the vagina.[1] Pain during intercourse can be a symptom. A longitudinal vaginal septum develops during embryogenesis when there is an incomplete fusion of the lower parts of the two Müllerian ducts. As a result, there may appear to be two openings to the vagina. There may be associated duplications of the more cranial parts of the Müllerian derivatives, a double cervix, and either a uterine septum or uterus didelphys (double uterus).[1][2] A transverse septum forms during embryogenesis when the Müllerian ducts do not fuse to the urogenital sinus. A complete transverse septum can occur across the vagina at different levels. Menstrual flow can be blocked, [3] and is a cause of primary amenorrhea. The accumulation of menstrual debris behind the septum is termed cryptomenorrhea. Some transverse septa are incomplete and may lead to dyspareunia or obstruction in labour.[4][5] ## See also[edit] * Diphallia ## References[edit] 1. ^ a b Heinonen, Pentti K. (2006-03-01). "Complete septate uterus with longitudinal vaginal septum". Fertility and Sterility. 85 (3): 700–705. doi:10.1016/j.fertnstert.2005.08.039. ISSN 0015-0282. PMID 16500341. 2. ^ Perez-Brayfield MR, Clarke HS, Pattaras JG (September 2002). "Complete bladder, urethral, and vaginal duplication in a 50-year-old woman". Urology. 60 (3): 514. doi:10.1016/S0090-4295(02)01808-3. PMID 12350504. 3. ^ "Urology Care Foundation - What Causes Congenital Vaginal Obstruction?". www.urologyhealth.org. Retrieved 2018-03-09. 4. ^ Üstün Y; Üstün YE; Zeteroğlu Ş; Şahin G; Kamacı M (2005). "A Case of Transverse Vaginal Septum Diagnosed During Labour" (PDF). Erciyes Medical Journal. 27 (3): 136–138. 5. ^ Dey, Pranab (2017-02-06). Essentials of Gynecologic Pathology. JP Medical Ltd. ISBN 9789386261205. ## External links[edit] Classification D * ICD-10: Q52.1 * ICD-9-CM: 752.49, 752.47, 752.46 Media related to Vaginal septum at Wikimedia Commons * Vagina, Anatomical Atlases, an Anatomical Digital Library (2018) * v * t * e Female congenital anomalies of the genitalia, including Intersex and DSD Internal Uterine malformation * Müllerian agenesis * Cervical agenesis * Unicornuate uterus * Uterus didelphys * Bicornuate uterus * Uterine septum * Arcuate uterus Vagina * Vaginal septum * Vaginal hypoplasia * Imperforate hymen * Vaginal adenosis * Cloacal exstrophy * Vaginal atresia External * Clitoromegaly * Progestin-induced virilization * Pseudohermaphroditism * True hermaphroditism [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Vaginal septum	c0266411	25,640	wikipedia	https://en.wikipedia.org/wiki/Vaginal_septum	2021-01-18T18:49:19	{"umls": ["C0266411"], "icd-9": ["752.49"], "icd-10": ["Q51.1"], "orphanet": ["180154"], "wikidata": ["Q7908507"]}
Salivary duct stricture (also termed salivary duct stenosis) is narrowing of the duct of a major salivary gland. ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 4 Treatment * 5 Epidemiology * 6 References ## Signs and symptoms[edit] Strictures are the second most common cause of chronic obstructive sialadenitis, after salivary stones.[1] In line with this, strictures may give rise to the "meal time syndrome",[1] where there is pain and swelling of the involved salivary gland upon salivary stimulation with the sight, smell and taste of food. In other cases, there is irregular and intermittent pain and swelling of the gland which is not related to meal times.[1] Typically the swelling is present upon waking or occurs before the first meal of the day. After several hours, the swelling goes down suddenly with a rush of foul tasting saliva.[1] Strictures are more common in the parotid duct system compared to the submandibular duct system.[2] ## Causes[edit] Chronic inflammation of the duct system (sialodochitis) may cause some segments of the duct to narrow due to fibrosis, and others to dilate.[2] Saliva stagnates and forms a mucus plug behind the stricture during sleep when the salivary output of the parotid is reduced. Then, when salivary secretion is stimulated, the mucus plug becomes stuck in the stricture.[1] The backlog of saliva behind the blockage causes the swelling, and the increased pressure inside the gland causes the pain. When the mucus plug is dislodged, the built up saliva is released and the swelling subsides. ## Diagnosis[edit] Strictures tend to be diagnosed based on difficulty with insertion and manipulation during sialendoscopy,[2] or by sialography or ultrasound.[1] ## Treatment[edit] Treatment is by endoscopic dilation, or failing this, surgery.[1] ## Epidemiology[edit] In one report, about 20% of individuals with mealtime syndrome had strictures upon sialography.[1] For unknown reasons, strictures seem to be more common in females.[1] ## References[edit] 1. ^ a b c d e f g h i McGurk M; Combes J (8 November 2012). Controversies in the Management of Salivary Gland Disease. OUP Oxford. pp. 287–299. ISBN 978-0-19-166809-8. 2. ^ a b c Bower CM; Richter GT (2014). Common ENT Disorders in Children. Elsevier Health Sciences. pp. 767–768, 771. 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syndrome * HIV salivary gland disease * Necrotizing sialometaplasia * Mucocele * Ranula * Pneumoparotitis * Salivary duct stricture * Salivary gland aplasia * Salivary gland atresia * Salivary gland diverticulum * Salivary gland fistula * Salivary gland hyperplasia * Salivary gland hypoplasia * Salivary gland neoplasms * Benign: Basal cell adenoma * Canalicular adenoma * Ductal papilloma * Monomorphic adenoma * Myoepithelioma * Oncocytoma * Papillary cystadenoma lymphomatosum * Pleomorphic adenoma * Sebaceous adenoma * Malignant: Acinic cell carcinoma * Adenocarcinoma * Adenoid cystic carcinoma * Carcinoma ex pleomorphic adenoma * Lymphoma * Mucoepidermoid carcinoma * Sclerosing polycystic adenosis * Sialadenitis * Parotitis * Chronic sclerosing sialadenitis * Sialectasis * Sialocele * Sialodochitis * Sialosis * Sialolithiasis * Sjögren's syndrome Orofacial soft tissues – Soft tissues around the mouth * Actinomycosis * Angioedema * Basal cell carcinoma * Cutaneous sinus of dental origin * Cystic hygroma * Gnathophyma * Ludwig's angina * Macrostomia * Melkersson–Rosenthal syndrome * Microstomia * Noma * Oral Crohn's disease * Orofacial granulomatosis * Perioral dermatitis * Pyostomatitis vegetans Other * Eagle syndrome * Hemifacial hypertrophy * Facial hemiatrophy * Oral manifestations of systemic disease [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Salivary duct stricture	c0266997	25,641	wikipedia	https://en.wikipedia.org/wiki/Salivary_duct_stricture	2021-01-18T18:57:33	{"umls": ["C0266997"], "wikidata": ["Q25339385"]}
Glomerulation refers to bladder hemorrhages which are thought to be associated with some types of interstitial cystitis (IC). The presence of glomerulations, also known as petechial hemorrhages, in the bladder suggests that the bladder wall has been damaged, irritated and/or inflamed. In fact, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Diagnostic Criteria for IC, developed in 1987, required the presence of glomerulations or Hunner's Ulcers for diagnosis of IC and is still used, today, to determine patient eligibility for some clinical trials.[1] Research conducted by Waxman,[clarification needed] however, determined that the hydrodistention procedure itself may have created these tiny broken blood vessels. Thus, a diagnosis of IC is now based upon other, less invasive methods, such as the PUF questionnaire. ## Contents * 1 Presentation * 2 Relation to Interstitial Cystitis * 3 Treatment * 4 References ## Presentation[edit] Glomerulations can be found in the 3 quadrants of the bladder, appearing as checkerboard/lattice patterns, splotches, or pinpoint-sized red marks on the bladder.[2][3] ## Relation to Interstitial Cystitis[edit] The identification of glomerulations as diagnostic criteria for interstitial cystitis/ bladder pain syndrome is unclear. [4] In 1987, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) developed diagnostic criteria for IC which included the presence of glomerulations or petechial hemorrhages.[1] The purpose of the NIDDK diagnostic criteria was to facilitate comparable patient groups for research.[5] It was not intended to set strict criteria for the diagnosis of IC. ## Treatment[edit] In addition to traditional IC therapies, diet modification remains a core self care strategy as foods that are irritating to the bladder dramatically worsen the symptoms that patients may experience. Foods high in acid and/or caffeine (such as all coffees, regular teas, green teas, sodas, diet sodas, artificial sweeteners and most fruit juices) should be avoided. The daily goal of patients should be to soothe rather than irritate the bladder wall. ## References[edit] 1. ^ a b Gillenwater Jay Y.; Wein Alan J. (1988). "Summary of the National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases Workshop on Interstitial Cystitis, National Institutes of Health, Bethesda, Maryland, August 28-29, 1987". Journal of Urology. 140 (1): 203–206. doi:10.1016/S0022-5347(17)41529-1. 2. ^ "How is a finding of glomerulations characterized in interstitial cystitis/bladder pain syndrome (IC/BPS)?". www.medscape.com. 2018. Retrieved 2020-07-28. 3. ^ "Cystoscopy with Hydrodistention". Interstitial Cystitis Association. 2015. Retrieved 2020-07-28. 4. ^ Wennevik Gjertrud E.; Meijlink Jane M.; Hanno Philip; Nordling Jørgen (2016). "The Role of Glomerulations in Bladder Pain Syndrome: A Review". Journal of Urology. 195 (1): 19–25. doi:10.1016/j.juro.2015.06.112. 5. ^ Hanno, Philip M (2002). "Interstitial Cystitis—Epidemiology, Diagnostic Criteria, Clinical Markers". Reviews in Urology. 4 (Suppl 1): S3–S8. ISSN 1523-6161. PMC 1476008. PMID 16986032. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Glomerulation	c1880960	25,642	wikipedia	https://en.wikipedia.org/wiki/Glomerulation	2021-01-18T18:31:21	{"umls": ["C1880960"], "wikidata": ["Q5571233"]}
Autosomal recessive spastic paraplegia type 44 (SPG44) is a very rare, complex form of hereditary spastic paraplegia characterized by a late-onset, slowly progressive spastic paraplegia associated with mild ataxia and dysarthria, upper extremity involvement (i.e. loss of finger dexterity, dysmetria), and mild cognitive impairment, without the presence of nystagmus. A hypomyelinating leukodystrophy and thin corpus callosum is observed in all cases and psychomotor development is normal or near normal. SPG44 is caused by mutations in the GJC2 gene (1q41-q42) encoding the gap junction gamma-2 protein. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Autosomal recessive spastic paraplegia type 44	c2750784	25,643	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=320401	2021-01-23T17:01:51	{"mesh": ["C567707"], "omim": ["613206"], "umls": ["C2750784"], "icd-10": ["G11.4"], "synonyms": ["SPG44"]}
Hand with multiple Bier spots Bier spots are small, light macules usually found on the arms and legs of young adults, in which the intervening skin may seem erthematous but blanches with pressure so that these light macules disappear.[1]:863 This is a benign physiologic vascular anomaly of no significance clinically.[1]:863[2]:819–20 ## Contents * 1 Diagnosis * 2 Treatment * 3 See also * 4 References * 5 Further reading ## Diagnosis[edit] The spots appear when the blood is congested with a bandage on the upper arm, e.g. with a blood pressure cuff. The spots also appear when the arms are slightly raised from the trunk (angle approx. 45°) and disappear again when the arms are stretched upwards.[3] ## Treatment[edit] It is a physiological phenomenon that requires no treatment.[3] ## See also[edit] * Marshall–White syndrome * List of cutaneous conditions ## References[edit] 1. ^ a b Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0. 2. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. 3. ^ a b "PharmaWiki - Bier-Flecken". www.pharmawiki.ch (in German). Retrieved 2020-06-10. ## Further reading[edit] * "Bier spots \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 20 September 2017. This cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Bier spots	c0406529	25,644	wikipedia	https://en.wikipedia.org/wiki/Bier_spots	2021-01-18T18:39:51	{"gard": ["13027"], "umls": ["C0406529"], "wikidata": ["Q4904603"]}
Uhl anomaly Other namesParchment right ventricle[1] Uhl anomaly is inherited via autosomal dominant manner SpecialtyMedical genetics The Uhl anomaly is a partial or total loss of the myocardial muscle in the right ventricle. A congenital heart disease, it is very rare: fewer than 100 cases in 1900–1993. It was first described in 1952 by Dr. Henry Uhl (1921–2009) upon examining one of his patients. [2] Three findings are enlarged right ventricular cavity without apical trabeculation with a thin hypokinetic ventricular wall.[3] ## References[edit] 1. ^ "Uhl anomaly \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 28 May 2019. 2. ^ Uhl, HS (1952). "A previously undescribed congenital malformation of the heart: almost total absence of the myocardium of the right ventricle". Bulletin of the Johns Hopkins Hospital. 91 (3): 197–209. PMID 12978573. 3. ^ Cardaropoli, D; Russo, MG; Paladini, D; Pisacane, C; Caputo, S; Giliberti, P; Calabrò, R (2006). "Prenatal echocardiography in a case of Uhl's anomaly". Ultrasound in Obstetrics & Gynecology. 27 (6): 713–4. doi:10.1002/uog.2798. PMID 16710881. ## Further reading[edit] * Gerlis, Leon (January 2003). "Uhl's anomaly" (PDF). Orphanet Encyclopedia. Orphanet. Retrieved November 16, 2010. "Summary". ## External links[edit] Classification D * ICD-9-CM: 746.8 (CDC/BPA 746.882) * OMIM: 107970 * MeSH: C536932 C536932, C536932 External resources * Orphanet: 3403 * 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 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-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Uhl anomaly	c0265857	25,645	wikipedia	https://en.wikipedia.org/wiki/Uhl_anomaly	2021-01-18T18:55:41	{"gard": ["5393"], "mesh": ["C536932"], "umls": ["C0265857"], "icd-9": ["746.8"], "orphanet": ["3403"], "wikidata": ["Q2852241"]}
Not to be confused with Spondylosis, Spondylitis, or Spondylolisthesis. Spondylolysis Spondylolysis SpecialtyOrthopedics Spondylolysis (spon-dee-low-lye-sis) is defined as a defect or stress fracture in the pars interarticularis of the vertebral arch.[1] The vast majority of cases occur in the lower lumbar vertebrae (L5), but spondylolysis may also occur in the cervical vertebrae.[2] ## Contents * 1 Signs and symptoms * 2 Cause * 2.1 Risk factors * 3 Pathophysiology * 4 Diagnosis * 4.1 One-legged hyperextension test * 4.2 X-Ray * 4.3 Bone scintigraphy * 4.4 Computed tomography * 4.5 MRI * 5 Treatment * 5.1 Conservative management * 5.1.1 Deep abdominal co-contraction exercises * 5.1.2 Activity restriction * 5.1.3 Bracing * 5.2 Surgery * 6 Implications for rehabilitation * 7 References * 8 External links ## Signs and symptoms[edit] In majority of cases, spondylolysis presents asymptomatically which can make diagnosis both difficult and incidental.[3] When a patient does present with symptoms, there are general signs and symptoms a clinician will look for: * Clinical Signs:[4][5] * Pain on completion of the stork test (placed in hyperextension and rotation) * Excessive lordotic posture * Unilateral tenderness on palpation * Visible on diagnostic imaging (Scottie dog fracture) * Symptoms:[4][5] * Unilateral low back pain * Pain that radiates into the buttocks or legs * Onset of pain can be acute or gradual * Pain that can restrict daily activities * Pain that worsens after strenuous activity * Pain aggravated with lumbar hyperextension * Difficulty in movement in spinalcord ## Cause[edit] The cause of spondylolysis remains unknown, however many factors are thought to contribute to its development. The condition is present in up to 6% of the population, majority of which usually present asymptomatically.[6] Research supports that there are hereditary and acquired risk factors that can make one more susceptible to the defect. The disorder is generally more prevalent in males compared to females, and tends to occur earlier in males due to their involvement in more strenuous activities at a younger age.[7] In a young athlete, the spine is still growing which means there are many ossification centers, leaving points of weakness in the spine. This leaves young athletes at increased risk, particularly when involved in repetitive hyperextension and rotation across the lumbar spine.[8] Spondylolysis is a common cause of low back pain in preadolescents and adolescent athletes, as it accounts for about 50% of all low back pain.[6] It is believed that both repetitive trauma and an inherent genetic weakness can make an individual more susceptible to spondylolysis.[4] ### Risk factors[edit] Sports involving repetitive or forceful hyperextension of the spine, especially when combined with rotation are the main mechanism of injury for spondylolysis. The stress fracture of the pars interarticularis occurs on the side opposite to activity. For instance, for a right-handed player, the fracture occurs on the left side of the vertebrae.[5] Spondylolysis has a higher occurrence in the following activities:[5] * Baseball * Military service * Tennis * Diving * Cheerleading * Gymnastics * Gridiron Football * Association Football * Wrestling * Weightlifting * Roller Derby * Cricket * Pole Vault * Rugby * Volleyball * Gym * Ultimate Frisbee (especially during impact from laying out) * Ballet * Muay Thai Although this condition can be caused by repetitive trauma to the lumbar spine in strenuous sports, other risk factors can also predispose individuals to spondylolsis. Males are more commonly affected by spondylolysis than females.[3] In one study looking at youth athletes, it was found that the mean age of individuals with spondylolisthesis was 20 years of age.[9] Spondylolysis also runs in families suggesting a hereditary component such as a predisposition to weaker vertebrae.[3] ## Pathophysiology[edit] Spondylolysis is a bony defect or fracture within the pars interarticularis of the vertebral arch in the spinal column. The vast majority of spondylolysis occur in the lumbar vertebrae, however it can also be seen in cervical vertebrae.[2] The lumbar vertebra consist of a body, pedicle, lamina, pars interarticularis, transverse process, spinous process and superior and inferior articular facets, which form joints that link the vertebrae together. When examining the vertebra, the pars interarticularis is the bony segment between the superior and inferior articular facet joints located anterior to the lamina and posterior to the pedicle. Separation of the pars interarticularis occurs when spondylolysis is present in the spinal column.[10] Spondylolysis is typically caused by a stress fracture of the bone, and is especially common in adolescents who over-train in activities. The pars interarticularis is vulnerable to fracture during spinal hyperextension, especially when combined with rotation, or when experiencing a force during a landing. This stress fracture most commonly occurs where the concave lumbar spine transitions to the convex sacrum (L5-S1). A significant number of individuals with spondylolysis will develop spondylolisthesis, which is true for 50-81% of this population.[11][3] Pars interarticularis marked with red lines ## Diagnosis[edit] There are several imaging techniques used to diagnose spondylolysis. Common imaging techniques include X-ray, MRI, Bone Scintigraphy (Bone Scan), and Computed Tomography (CT Scan). Qualified health care practitioners are also able to conduct clinical tests such as the one-legged hyperextension test to diagnose active spondylolysis.[12] ### One-legged hyperextension test[edit] This is a test conducted by a qualified healthcare practitioner within a clinical setting. It involves having the patient stand upon one leg and then lean backwards. The test should produce pain on the same side of the spine as the leg that you are standing on. If it produces pain this indicates spondylolysis on that side. The test is then performed on the other side assessing for pain again. The test can be positive on one side, both sides or neither.[12] ### X-Ray[edit] X-rays (electromagnetic radiation) are projected through the body to produce an image of its internal structures. The radiation is more attenuated (absorbed) by the denser tissues of the body (i.e. bone) than the softer tissues (i.e. muscles, organs, etc) creating a picture composed of shades of grey ranging from white to black. A vertebra with a fracture or defect of the pars interarticularis will have a dark mark through this region of bone. Since this is difficult to see on the AP (anterior posterior) x-ray view an oblique x-ray of the lumbar spine can usually identify the spondylolysis. If inconclusive a further CT scan can produce a 3-dimensional images to more clearly show the defect although the exam increases the patients radiation dose by at least an order of magnitude than plain x-rays.[12][13] ### Bone scintigraphy[edit] Bone scintigraphy showing black marks where pelvic bone damage has occurred. Also known as a bone scan, bone scintigraphy involves the injection of a small amount of radioactive tracer into the bloodstream. This tracer decays and emits radioactive energy which can be detected by a special camera. The camera produces a black and white image where areas shown as dark black indicate bone damage of some kind. If there is a black spot in the lumbar vertebrae (e.g. L5) this indicates damage and potentially spondylolysis. If this test is positive, a CT scan is usually ordered to confirm spondylolysis.[12] ### Computed tomography[edit] Cross-sectional image of a vertebra showing spondylolysis. Commonly known as a CT Scan or CAT scan, this form of imaging is very similar to x-ray technology but produces many more images than an x-ray does. The multiple images produce cross-sectional views not possible with an x-ray. This allows a physician or radiologist to examine the images from many more angles than an x-ray allows. For this reason the CT scan is much more accurate in detecting spondylolysis than an x-ray. Bone scintigraphy combined with CT scan is considered the gold standard which means that it is best at detecting spondylolysis.[12][14] ### MRI[edit] MRI is a newer technique used to diagnose spondylolysis and is favorable for a few reasons. The MRI is much more accurate than the x-ray and also does not use radiation. The MRI uses powerful magnets and radio frequencies to produce very detailed images of many different densities of tissue including bone and soft tissues.[12][15] ## Treatment[edit] ### Conservative management[edit] Treatment for spondylolysis ranges from bracing, activity restriction, extension exercises, flexion exercises and deep abdominal strengthening, that is administered through physical therapy. The duration of physical therapy a patient receives varies upon the severity of spondylolysis, however typically ranges from three to six months. The goal of physical therapy is to minimize movement at the unstable defect of the pars interarticularis. Once a patient completes physical therapy, and displays no symptoms or inflammation in the lower back, they are cleared to continue with daily or athletic activities. However, a patient may need to maintain a variety of rehabilitation techniques after physical therapy to prevent the recurrence of spondylolysis.[16] #### Deep abdominal co-contraction exercises[edit] The aim of deep abdominal co-contraction exercises is to train muscles surrounding the lumbar spine which provide stability of the spine. Spondylolysis results in a spinal instability and disrupts patterns of co-recruitment between muscle synergies. Specifically, local muscles that attach directly to the spine are affected. The lumbar multifidis and transversus abdominis play a direct role in stabilizing the lumbar spine. Instead the local muscles in individuals with spondylolysis are vulnerable to dysfunction, which results in abnormal spinal stability causing chronic low back pain. To compensate, the large torque producing global muscles are used to stabilize the spine.[17] In one study, patients are taught to train the co-contraction of deep abdominal muscles and lumbar multifidus in static postures, functional tasks and aerobic activities. This technique was shown to reduce pain and functional disability when compared to other conservative treatments. These results also had a long- term effect in reducing levels of pain and functional disability. This is because motor programming eventually became automatic, and conscious control was no longer needed to contract the deep abdominal muscles during activities.[17] #### Activity restriction[edit] Activity restriction of spondylolysis is advised for a short period of time once the patient becomes symptomatic, followed by a guided physical therapy program. Once spondylolysis has been diagnosed, treatment often consists of a short rest period of two to three days, followed by a physical therapy program. There should be restriction of heavy lifting, excessive bending, twisting and avoidance of any work, recreational activities or participation in sport that causes stress to the lumbar spine.[18] Activity restriction can help eliminate and control a patient's symptoms so they are able to resume their normal activities.[19] Activity restriction is most commonly used in conjunction with other rehabilitation techniques including bracing.[citation needed] #### Bracing[edit] Antilordotic lumbrosacral brace (Boston brace) Acute spondylolysis is most commonly treated through the use of an anti-lordotic brace (Boston brace) to control and limit spinal movement, and reduce stress on the injured spinal segment.[18][20] Bracing immobilizes the spine in a flexed position for a short period to allow healing of the bony defect in the pars interarticularis.[20][21] An antilordotic brace commonly utilizes a plastic component that is contoured to closely fit the body.[20] Antilordotic bracing subsequently reduces the athlete’s symptoms by decreasing the amount of stress on the low back, and allows a prompt return to sport for athletes.[18] Typically, bracing is utilized for 6–12 weeks.[21] In order for a brace to be effective, it must be worn every day for the required amount of time. Patients are given a brace schedule determined by their physical therapist that explains the amount of time the brace must be worn daily. A brace's effectiveness increases with adherence to the bracing schedule. Patients that do not follow their bracing schedule are more likely to have their symptoms progress.[21] Research has demonstrated that when braces are used as prescribed with full compliance, they are successful at preventing spondylolysis progression.[18] ### Surgery[edit] Most patients with spondylolysis do not require surgery but, if the symptoms are not relieved with non-surgical treatments, or when the condition progresses to high grade spondylolisthesis, then patients may require surgery. There are two main types of surgery for this condition:[22] * Spinal fusion: This procedure is recommended when a set of vertebrae becomes loose or unstable. The surgeon joins two or more bones (vertebrae) together through the use of metal rods, screws, and bone grafts. The bone grafts complete their fusion in 4–8 months following the surgery, securing the spine in the correct position. The procedure is also used to treat spinal instability, fractures in the lumbar spine and, severe degenerative disc disease. The process is relatively non-invasive, performed through small incisions and has a high success rate.[22] * Laminectomy: Often performed when spinal stenosis occurs in conjunction with spondylolysis. The procedure surgically removes part or all of the lamina from the bony ring of the vertebra to reduce the pressure on the spinal cord. The laminectomy is commonly performed on the vertebrae in the lower back and in the neck.[22] ## Implications for rehabilitation[edit] Spondylolysis can have a huge impact on a young athlete's career, and may impede their future ability to perform.[23] It is important to understand how social and psychological factors may affect rehabilitation of an injured athlete. Frustration, anger, confusion, fear and depression are some of the psychological factors that injured athletes experience, therefore a debilitating injury can have a large impact on an athlete's mental well-being.[24] These psychological factors can also affect recovery and return to sport as fear of re-injury often prevents athletes from adhering to rehabilitation and returning to their sport at full intensity.[23] Social factors can also impact the cognitive, behavioural and physical responses to injury. More specifically, social isolation from the team can have a profound psychological effect. This makes it essential to provide social support through supportive listening, emotional support, personal assistance and reality conformation.[23] It is also critical to educate the athletes on the rehabilitation process so they know what to expect. For instance, explaining what activities to avoid and will cause pain as well as the duration of the treatment process. In addition, it is important to select the correct treatment option for each individual. For conservative methods, adherence to the exercise requires motivated patients as it can be tedious and time consuming. For instance, one study looking at deep abdominal co-contraction reported that it can take as long a 4–5 weeks to achieve this pattern of co-contraction.[17] ## References[edit] 1. ^ Iwamoto, J., Takeda, T., Wakano, K. Returning athletes with severe low back pain and spondylolysis to original sporting activities with conservative treatment. Sports Scandinavian Journal of Medicine and Science in Sports. 2004;14(6):346–351. 2. ^ a b Dubousset, J. Treatment of Spondylolysis and Spondylolisthesis in Children and Adolescents. Clinical Orthopaedics and Related Research. 1997;337:77–85. 3. ^ a b c d Syrmou, E., Tsitsopoulos, P. P., Marinopoulos, D., Tsonidis, C., Anagnostopoulos, I., & Tsitsopoulos, P. D.Spondylolysis: A Review and Reappraisal. H Quarterly Medical Journal. 2010;14(1): 17–21 4. ^ a b c Spondylolysis and Spondylolisthesis of the Lumbar Spine. Children's Orthopaedics, Mass General. Available at: http://www.massgeneral.org/ortho-childrens/conditions-treatments/spondylolysis.aspx. Accessed March 28, 2016 5. ^ a b c d Humphreys, D. Lecture on Spondylolysis and Spondylolisthesis. [OWL]. Western University Kinesiology Program; 2015. 6. ^ a b McTimoney, M. & Micheli, L. J. Current Evaluation and Management of Spondylolysis and Spondylolisthesis. Current Sports Medicine Reports. 2003, 2:41–46 7. ^ Canzonieri, C., & Pilloud, M. A. The Occurrence and Possible and Aetiology of spondylolysis in a Pre-Contact California Population. International Journal of Osteoarchaeology. 2012, 24:602-613 8. ^ McCleary, M. D. and Congeni, J. A. Current concepts in the diagnosis and treatment of spondylolysis in young athletes. Current sports medicine reports. 2007;6(1):62-66. 9. ^ Debnath, U. K., Freeman, B. J. C., Gregory, P., de la Harpe, D., Kerslake, R. W. and Webb, J.K. Clinical outcome and return to sport after the surgical treatment of spondylolysis in young athletes. Journal of Bone and Joint Surgery, British Volume. 2003, 85(2): 244-249. 10. ^ Standaert, C.J., Herring, S.A., Cole, A.J., Stratton, S.A. The Lumbar Spine and Sports. Low Back Pain Handbook. 2003:385–404. 11. ^ Cianfoni A, Cerase A, Magarelli N, Bonomo L. Lumbar spondylolysis: a review. Skeletal Radiology. 2011;40:683-700. 12. ^ a b c d e f Masci L, Pike J, Malara F, Phillips B, Bennell K, Brukner P. Use of the one-legged hyperextension test and magnetic resonance imaging in the diagnosis of active spondylolysis.British Journal of Sports Medicine. 2006;40:940-946. 13. ^ X-ray: MedlinePlus Medical Encyclopedia. US National Library of Medicine. 2014. Available at: https://www.nlm.nih.gov/medlineplus/ency/article/003337.htm. Accessed March 30, 2016. 14. ^ Body CT (CAT Scan). Body CT (CAT Scan). 2016. Available at: http://www.radiologyinfo.org/en/info.cfm?pg=bodyct. Accessed March 30, 2016. 15. ^ Body MRI - magnetic resonance imaging of the chest, abdomen and pelvis. Body MRI - magnetic resonance imaging of the chest, abdomen and pelvis. 2014. Available at: http://www.radiologyinfo.org/en/info.cfm?pg=bodymr. Accessed March 30, 2016. 16. ^ Pizzutillo, PD, Hummer, CD. Nonoperative Treatment for Painful Adolescent Spondylolysis or Spondylolisthesis. Journal of Pediatric Orthopaedics. 1989;9(5):538–540. 17. ^ a b c O'Sullivan, P. B., Phyty, D. M., Twomey, L. T., & Allison, G. T.Evaluation of Specific Stabilizing Exercise in the Treatment of Chronic Low Back Pain with Radiologic Diagnosis of Spondylolysis or Spondylolisthesis. Spine. 1997, 22(24):2959-2967. 18. ^ a b c d Iwamoto, J. Return to sports activity by athletes after treatment of spondylolysis. World Journal of Orthopedics. 2010;1(1):26. 19. ^ Bergmann TF, Hyde TE, Yochum TR. Active or Inactive Spondylolysis and/or Spondylolisthesis: What's the Real Cause of Back Pain? Journal of the Neuromusculoskeletal System. 2002:10:70-78. 20. ^ a b c Boston Brace: The Orthotics and Prosthetics Leaders. Boston Overlap Brace. Boston Overlap Brace. Available at: http://www.bostonbrace.com/content/boston_overlap_brace.asp. Accessed March 27, 2016. 21. ^ a b c Parkview Spine Institute. Treatment Options for Pediatric/Adolescent Spondylolysis and Spondylolisthesis - Parkview Orthopedics. Parkview Orthopedics. Available at: http://parkviewspine.com/patient-education/treatment-options-for-pediatricadolescent-spondylolysis-and-spondylolisthesis/. Accessed March 27, 2016. 22. ^ a b c Deguchi M, Rapoff AJ, Zdeblick TA. Posterolateral fusion for isthmic spondylolisthesis in adults: Analysis of fusion rate and clinical results. Journal of Spinal Disorders. 1998;11:459-464. 23. ^ a b c Tenenbaum, G. & Eklund, RC. Handbook of Sport Psychology. Psychology. John Wiley & Sons Inc. 2007, 3 24. ^ Klenk, CA. Psychological Response to Injury, Recovery and Social Support: A Survey of Athletes at an NCAA Division I University Digital Commons at University of Rhode Island. Senior Honors Project. 2006. ## External links[edit] Classification D * ICD-10: M43.0 * ICD-9-CM: 738.4 * MeSH: D013169 * DiseasesDB: 12322 * SNOMED CT: 240221008 External resources * eMedicine: radio/650 * v * t * e Spinal disease Deforming Spinal curvature * Kyphosis * Lordosis * Scoliosis Other * Scheuermann's disease * Torticollis Spondylopathy inflammatory * Spondylitis * Ankylosing spondylitis * Sacroiliitis * Discitis * Spondylodiscitis * Pott disease non inflammatory * Spondylosis * Spondylolysis * Spondylolisthesis * Retrolisthesis * Spinal stenosis * Facet syndrome Back pain * Neck pain * Upper back pain * Low back pain * Coccydynia * Sciatica * Radiculopathy Intervertebral disc disorder * Schmorl's nodes * Degenerative disc disease * Spinal disc herniation * Facet joint arthrosis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Spondylolysis	c0038018	25,646	wikipedia	https://en.wikipedia.org/wiki/Spondylolysis	2021-01-18T18:56:08	{"mesh": ["D013169"], "umls": ["C0038018"], "icd-9": ["738.4"], "wikidata": ["Q2000072"]}
Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a disorder that causes progressive dysfunction of the brain (encephalopathy). It is characterized by a loss of intellectual functioning (dementia) and seizures. At first, affected individuals may have difficulty sustaining attention and concentrating. They may experience repetitive thoughts, speech, or movements. As the condition progresses, their personality changes and judgment, insight, and memory become impaired. Affected people lose the ability to perform the activities of daily living, and most eventually require comprehensive care. The signs and symptoms of FENIB vary in their severity and age of onset. In severe cases, the condition causes seizures and episodes of sudden, involuntary muscle jerking or twitching (myoclonus) in addition to dementia. These signs can appear as early as a person's teens. Less severe cases are characterized by a progressive decline in intellectual functioning beginning in a person's forties or fifties. ## Frequency This condition appears to be rare; only a few affected individuals have been reported worldwide. ## Causes FENIB results from mutations in the SERPINI1 gene. This gene provides instructions for making a protein called neuroserpin, which is found in nerve cells (neurons). Neuroserpin plays a role in the development and function of the nervous system. This protein helps control the growth of neurons and their connections with one another, which suggests that it may be important for learning and memory. Mutations in the SERPINI1 gene result in the production of an abnormally shaped, unstable form of neuroserpin. Within neurons, defective neuroserpin proteins can attach to one another and form clumps called neuroserpin inclusion bodies or Collins bodies. These clumps disrupt the cells' normal functioning and ultimately lead to cell death. The gradual loss of neurons in certain parts of the brain causes progressive dementia. Researchers believe that a buildup of related, potentially toxic substances in neurons may also contribute to the signs and symptoms of this condition. ### Learn more about the gene associated with Familial encephalopathy with neuroserpin inclusion bodies * SERPINI1 ## Inheritance Pattern FENIB is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In many cases, an affected person has a parent with the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Familial encephalopathy with neuroserpin inclusion bodies	c1858680	25,647	medlineplus	https://medlineplus.gov/genetics/condition/familial-encephalopathy-with-neuroserpin-inclusion-bodies/	2021-01-27T08:25:32	{"gard": ["10037"], "mesh": ["C536841"], "omim": ["604218"], "synonyms": []}
This article needs attention from an expert on the subject. Please add a reason or a talk parameter to this template to explain the issue with the article. When placing this tag, consider associating this request with a WikiProject. (May 2010) Sialadenitis(Sialoadenitis) Micrograph showing chronic sialadenitis. H&E stain. SpecialtyOtorhinolaryngology Sialadenitis (sialoadenitis) is inflammation of salivary glands, usually the major ones, the most common being the parotid gland, followed by submandibular and sublingual glands.[1] It should not be confused with sialadenosis (sialosis) which is a non-inflammatory enlargement of the major salivary glands.[2] Sialadenitis can be further classed as acute or chronic. Acute sialadenitis is an acute inflammation of a salivary gland which may present itself as a red, painful swelling that is tender to touch. Chronic sialadenitis is typically less painful but presents as recurrent swellings, usually after meals, without redness.[1] Causes of sialadenitis are varied, including bacterial (most commonly Staphylococcus aureus), viral and autoimmune conditions.[1][3] ## Contents * 1 Types * 1.1 Acute * 1.2 Chronic * 2 Signs and Symptoms * 2.1 Acute * 2.2 Chronic * 2.3 Autoimmune * 2.4 Infection * 2.5 Complications * 3 Causes * 4 Histopathology * 4.1 Infective sialadenitis * 4.2 Chronic sialadenitis * 4.3 Autoimmune sialadenitis * 5 Diagnosis * 5.1 Acute bacterial sialadenitis * 5.2 Chronic recurrent sialadenitis * 5.3 Chronic sclerosing sialadenitis * 5.4 Obstructive sialadenitis * 5.5 Autoimmune sialadenitis * 5.5.1 Diagnostic tests * 6 Treatment * 7 Epidemiology * 8 See also * 9 References * 10 External links ## Types[edit] ### Acute[edit] Predisposing factors * sialolithiasis * decreased flow (dehydration, post-operative, drugs) * poor oral hygiene * exacerbation of low grade chronic sialoadenitis Clinical features * painful swelling * reddened skin * edema of the cheek, periorbital region and neck * low grade fever * malaise * raised ESR, CRP, leucocytosis * purulent exudate from duct punctum ### Chronic[edit] Main article: Chronic sclerosing sialadenitis Clinical features * unilateral * mild pain / swelling * common after meals * duct orifice is reddened and flow decreases * may or may not have visible/palpable stone. * Parotid gland * recurrent painful swellings * Submandibular gland * usually secondary to sialolithiasis or stricture ## Signs and Symptoms[edit] Sialadenitis is swelling and inflammation of the parotid, submandibular, or sublingual major salivary glands. It may be acute or chronic, infective or autoimmune. ### Acute[edit] * Acute sialadenitis secondary to obstruction (sialolithiasis) is characterised by increasingly, painful swelling of 24–72 hours, purulent discharge and systemic manifestations. ### Chronic[edit] * Chronic sialadenitis causes intermittent, recurrent periods of tender swellings. Chronic sclerosing sialadenitis is commonly unilateral and can mimic a tumour. ### Autoimmune[edit] * Autoimmune sialadenitis (i.e Sjogren’s syndrome) causes unilateral or bilateral painless swellings unless there is a secondary infection.[4] ### Infection[edit] * The most common salivary gland infection is mumps. It is characterised by bilateral swelling of the parotid glands, however other major salivary glands may also be affected in around 10% of cases. The swelling persists for about a week, along with low grade fever and general malaise. * Recurrent parotitis of childhood is characterised by periods of pain and swelling in the parotid gland accompanied by a fever[5] ### Complications[edit] COMPLICATION TIMEFRAME LIKELIHOOD Abscess Infection may spread along the fascial planes of the neck causing a potentially serious complication. Seldomly this can affect the spaces in the floor of the mouth and can result in Ludwig angina. Short term Medium Dental decay Hypofunction of the salivary gland will reduce saliva production causing decreased protection against acid erosion and increased risk of dental decay. Long term High Postparotidectomy complications (facial deformity or facial nerve palsy) Temporary facial nerve palsy occurs in around one third to two thirds of patients following superficial parotidectomy. Cosmetic deformity is relatively minor, although symptoms may recur in up to 11-13%, of these not all require further treatment. The occurrence of recurrent symptoms is lower (4%) for subtotal parotidectomy. The choice of the surgical procedure is determined by the extent of the disease and the patient’s preference. The pattern of facial weakness is likely to include one or more branches of the nerve and is likely to be panfacial due to the widespread fibrosis within the gland. Normally complete recovery occurs within 3 to 6 months with permanent palsy occurring in <1%.The prevalence of seroma, haematoma or significant infection should be less than 5%.[4] Variable Low ## Causes[edit] Sialadenitis can be caused by cancer, autoimmune conditions, viral and bacterial infections, idiopathic causes or stones formed mainly from calculus.[6] It was thought that morphological characteristics of the salivary ducts could also be a contributing factor, as stagnation of saliva due to these could perhaps cause an increased incidence of sialadenitis.[7] However, one study found no statistically significant difference between the length of ducts or the angles they incorporate within them and the likelihood of developing sialadenitis, although this study only had a small sample size of 106.[7] The study also confirmed that age, gender, side of face and degree of sialadenitis had no impact on the length of the ducts or the angles formed within the ducts.[7] Viral pathogens more commonly cause sialadenitis in comparison to bacterial pathogens.[6] Mumps is the most common virus that affects the parotid and submandibular glands, with the parotid gland affected most often out of these two.[6] Other viruses that have been shown to cause sialadenitis in both these glands include HIV, coxsackie, and parainfluenza.[6] Classically, HIV parotitis is either asymptomatic or a non-painful swelling, which is not characteristic of sialadenitis.[6] Some common bacterial causes are S. aureus, S. pyogenes, viridans streptococci and H. influenzae.[6] Autoimmune conditions that can cause sialadenitis include Sjögren’s syndrome, sarcoidosis, and granulomatosis with polyangiitis.[6] Sjögren’s syndrome and Sarcoidosis are the most common causes of chronic sialadenitis and are often closely associated with it, and in many cases are believed to be the primary cause, although often with other contributing factors present also.[6] One well known form of sarcoidosis is known as Heerfordt’s syndrome which is characterized by facial nerve palsy, enlargement of the parotid and anterior uveitis.[6] One study came to the conclusion that the presence of salivary calculi is the main indicator for the removal of the submandibular gland, in patients where neoplasia is absent.[8] This was because 82% of glands removed in an ENT department in Stockholm were found to have salivary calculi within them and all of these cases but one had chronic sialadenitis.[8] A mucous retention cyst was found in one patient, but this was not considered to have contributed to the sialadenitis in this case.[8] The duration of the sialadenitis was found to be closely linked to atrophy, fibrosis and the degree of the inflammation in another study, which looked primarily at microliths found in the ducts and glands.[9] Liths were also found to be related to the duration that the individual had symptoms of sialadenitis, whereas microliths were found in normal glands and varied with age.[9] Microliths could possibly form reservoirs, thus allowing infection to ascend further towards the glands but this could not be confirmed due to the liths and microliths being distinct in this study.[9] However, many glands did show only very minimal variations, which could allow the opportunity for more conservative treatment instead of the surgical removal of the affected gland in the future.[9] ## Histopathology[edit] Initial stage of acute bacterial sialadenitis involves[10] the accumulation of bacteria, neutrophils and inspissated fluid in lumen of ductal structures. Damage to ductal epithelium results in sialodochitis (periductal inflammation), accumulation of neutrophils in glandular stroma, followed by acini necrosis with microabscesses formation. Recurrent episodes results in chronic stage, which involves the establishment of periductal lymph follicles and further destruction of salivary acini.[10] ### Infective sialadenitis[edit] Generally, in acute bacterial and viral sialadenitis cases, the lobular architecture of the gland is maintained or may be slightly expanded. Areas of liquefaction, indicating presence of abscess, may also be seen microscopically. In Acute bacterial sialadenitis, acinar destruction with interstitial neutrophil infiltrates is observed. Small abscesses with necrosis are common. In Viral sialadenitis, vacuolar changes are seen in the acini with lymphocytic and monocytic infiltrate found in the interstitium Cytomegalovirus (CMV) sialadenitis may show no gross symptoms Chronic sialadenitis (also known as lymphoepithelial sialadenitis (LESA)) presents with 50% of which are monoclonal by PCR while mucosa-associated lymphoid tissue (MALT) lymphoma has ducts surrounded by broad coronas of monocytoid cells, infiltration of interfollicular region by monocytoid cells or atypical plasma cells containing Dutcher bodies, monoclonality by immunohistochemistry or flow cytometry, and monocytoid infiltrates in regional lymph nodes.[11] Histologically, chronic sialadenitis can appear from unremarkable to a firm tan with expansion or atrophy of the lobular structure depending on the degree of inflammation and chronicity. Salivary stones (Sialolith) may be evident with cystic dilation of the salivary ducts and periductal fibrosis. Mucus extravasation may also be observed. Common observations of chronic sialadenitis include chronic inflammatory infiltrate (lymphocytes, plasma cells and macrophages), fibrosis, acinar atrophy, mucous cell metaplasia of the ductal system is observed. In Sialoithiasis, concomitant squamous metaplasia may be observed in the salivary ducts with dark calcific stone fragments. ### Chronic sialadenitis[edit] Chronic sclerosing sialadenitis has various degrees of inflammation which can include focal lymphocytic sialadenitis to widespread salivary gland cirrhosis with obliteration of acini. This can be a result of obstruction of salivary ducts by microliths (due to associated intercurrent infections), or a result of immune reaction with the formation of secondary lymph follicles.[10] Chronic sclerosing sialadenitis is characterised by presence of three major criteria of[11] dense lymphoplasmacytic infiltrate, storiform pattern of fibrosis and obliterative phlebitis. Minor criteria include phlebitis without obliteration of the lumen and increased numbers of eosinophils. There are two features relatively inconsistent with diagnosis of IgG4-related disease which are the presence of epithelioid cell granulomas and a prominent neutrophilic infiltrate.[11] Sclerosing polycystic sialadenitis histologically resembles sclerosing adenosis/fibrocystic change of breast tissue. It composes of acini and ductal elements embedded in dense sclerotic stroma, and has a characteristic finding of large acinar cells present with abundant eosinophilic cytoplasmic granules. In addition, it may also present ductal epithelial proliferation which could range from hyperplasia, atypia to DCIS-like. Its stroma may show focal adipose tissue with myxoid change and variable radial scar. At present, there are immunohistochemical studies of limited value only. It is cytologically difficult to diagnose this type of sialadenitis due to the rarity of this condition and the presence of variable cell types in a cystic background.[11] In autoimmune sialadenitis, activation of T and B cells that infiltrate the interstitium occurs due to a response to an unidentified antigen present in the salivary gland parenchyma. This response then results in acini destruction and the formation of epimyoepithelial islands.[10] ### Autoimmune sialadenitis[edit] Most histological appearance of autoimmune sialadenitis are similar to that of Myoepithelial sialadenitis. In general, a diffuse to multinodular expansion is observed in myoepithelial sialadenitis. A distinguishing feature is the presence of epithelial-myoepithelial islands infiltrated by lymphocytes. Germinal centers may form with the progression of lymphoid infiltrate resulting in acinar atrophy. Proliferation of ductal epithelium-myoepithelium arises causing the obliteration of ductal lumina causing the formation of the epithelial-myoepithelial islands. Granulomatosis with polyangiitis may have areas of liquefaction necrosis caused by vasculitis. A triad of vasculitis, necrosis and granulomatous inflammation may be observed. In secondary Sjogren’s syndrome, periglandular fibrosis with the absence of inflammation may also be observed in addition to that of Myoepithelial sialadenitis from the progressive systemic sclerosis. Sarcoid has tight epithelioid granulomas and lymphoid infiltrate. Chronic Sclerosing Sialadenitis has peridutcal fibrosis with a dense lymphoplasmacytic infiltrate with lymphoid follicles. Eosinophils may be seen. ## Diagnosis[edit] According to the British Medical Journal (BMJ) Best Practice on Sialadenitis, there are multiple factors to consider during the diagnosis of sialadenitis, including history, presenting signs and symptoms, followed by appropriate investigations in relation to the presenting case. Other factors to also consider include the type of gland affected as well as underlying conditions such as an autoimmune disease or ductal stones.[10] ### Acute bacterial sialadenitis[edit] May present with a history of recent surgical intervention or use of medications such as antihistamines, antidepressants, or anticholinergic agents. These medications may lead to objective hypofunction or subjective feeling of a dry mouth without hypofunction. There may also be a history of decrease in salivary volume secondary to a systemic disease. A unilateral or bilateral painful swelling of the parotid or submandibular regions may be present upon a physical examination. This could be accompanied by an external displacement of the earlobe usually adjacent to an inflamed parotid gland. Pus suppuration from major salivary gland duct openings may occur spontaneously or after manipulation of the affected gland. Mandibular trismus is a rare finding but may be present with larger swellings. Dysphagia may also be present in some cases. Fever may also be noted, whilst spiking temperatures may be suggestive of an abscess formation. ### Chronic recurrent sialadenitis[edit] The occurrence of chronic recurrent episodes may be due to underlying Sjogren's syndrome or ductal abnormalities. Prodrome of tingling in the gland preceding pain and swelling may be reported in such cases. ### Chronic sclerosing sialadenitis[edit] Typically presents unilaterally in submandibular gland that cannot be differentiated clinically from a neoplasm, with pain an inconsistent finding. ### Obstructive sialadenitis[edit] Formation of stones in glandular ducts (sialoliths) can result in the development of obstructive sialadenitis. There may be a history of abrupt episodic swelling of the parotid or submandibular gland which is usually painful. These episodes typically occur around meal times, lasting 2 – 3 hours and gradually subsides. ### Autoimmune sialadenitis[edit] Characterised by persistent, asymptomatic bilateral swelling of parotid glands, and may represent as a manifestation of more widespread systemic disease. Dry eyes and dry mouth are commonly present and may be indicative of concomitant connective tissue disease (e.g. SLE, RA, or scleroderma). Oral candidiasis may also be present. Common key diagnostic factors 1\. Fever – may present with an acute infective sialadenitis or autoimmune aetiology suggestive of an infection or inflammation. 2\. Pain and dysphagia (ie. difficulty swallowing) – usually unilateral affecting the parotid or submandibular regions, with worse pain during eating and swallowing. 3\. Facial swelling – usually unilaterally and affecting parotid region, under the tongue, or below the jaw. May have acute onset and may have a history of repeated episodes. 4\. Recurrent painful swellings – indicative of chronic recurrent sialadenitis, may have similar signs and symptoms to an acute episode. 5\. Pus exudation from salivary gland openings – indicative of bacterial infection, may occur on manipulation of the affected gland or spontaneously. Other common diagnostic factors to consider 1\. Episodic swelling during meal times – may present as an acute salivary gland swelling without visible salivary flow from ductal openings. While palpation of affected glad may reveal an indurated salivary gland and presence of a sialolith. 2\. Use of xerostomic medications – these medications will result in a decreased salivary flow rate which can predispose to infections of glands. Examples of medications that may contribute to this include antihistamines, antidepressant, and anticholinergic agents. 3\. Recent surgical intervention under general anaesthetic – this could predispose to sialadenitis due to direct effects of anaesthetic agents used and volume depletion from surgery. 4\. Dry eyes and mouth – dryness affecting the eyes and oral cavity are key symptoms of Sjogren’s syndrome and may be seen in combination with a connective tissue disease such as rheumatoid arthritis, scleroderma, or dermatomyositis. 5\. Oral candidiasis – may be present in cases of Sjogren’s syndrome or in associate with a connective tissue disorder. Key factors to also consider which are less common 1\. Mandibular trismus – restricted mouth opening to its full extent (of approximately 40mm) may be present with large swellings typically due to acute bacterial infection of affected gland. 2\. Respiratory distress – this could present in the form of stridor, use or reliance on accessory muscles of respiratory, nasal flaring, or wheeze. These signs may develop if glandular swelling is significant enough, resulting in airway obstruction. 3\. Cranial nerve palsy – swelling increases the risk of compression of cranial nerves VII, IX and XII. Other diagnostic factors which are less common 1\. Connective tissue disorder or Sjogren’s syndrome – history of Sjogren’s syndrome, or a concomitant connect tissue disorder such as systemic lupus erythematosus, rheumatoid arthritis, or scleroderma. 2\. Recurrent painless swellings – indicative of underlying autoimmune aetiology. 3\. Displacement of earlobe – may be present when swelling of the parotid gland is present. 4\. Prodrome of tingling in the affected gland 5\. Swelling on hard palate #### Diagnostic tests[edit] Tests available as part of diagnosing sialadenitis include: 1. Culture and sensitivity testing of exudate from salivary duct. Culturing of purulent discharge is advisable in acute presentations of sialadenitis to allow targeted antibiotic therapy. 2. Full blood count if infection is suspected. 3. Facial radiographs such as dental radiographic views should be taken to exclude an obstructive element due to presence of sialolith or evolving abscess. However, sialoliths with low calcium phosphate content may not be visible. ## Treatment[edit] In chronic recurrent sialadenitis or chronic sclerosing sialadenitis, acute attacks are managed with conservative therapies such as hydration, analgesics (mainly NSAIDs), sialogogues to stimulate salivary secretion, and regular, gentle gland massage.[12] If infection is present, appropriate cultures should be obtained, followed by empirical antibiotic therapy initially,[12] for example amoxicillin/clavulanate or clindamycin which cover oral flora. If there are attacks more than approximately 3 times per year or severe attacks, surgical excision of the affected gland should be considered.[12] ## Epidemiology[edit] Sialadenitis of the parotid gland accounts for a much larger percentage of hospital admissions than sialadenitis of the submandibular gland.[6] Submandibular sialadenitis has been said to only account for 10% of all cases diagnosed as sialadenitis.[6] Chronic sialadenitis has been classified as a relatively common presentation, whereas bacterial sialadenitis and sclerosing polycystic sialadenitis are defined as rare.[11] Chronic sclerosing sialadenitis has been shown to affect predominantly males who are over the age of 50, with 40% of cases having an allergic disease, such as chronic sinusitis or bronchial asthma.[11] One study found that 112 patients from England and Wales ranging from 12 to 81 years of age complained of symptoms from their diagnosed sialadenitis, with the group having a mean age of 39 and a standard deviation of 16 years.[4] The study also found that more patients underwent surgery to treat their sialadenitis between the ages of 20 and 69 years but that there were many more patients who complained of symptoms between the ages of 20 and 49, and then went on to be diagnosed with sialadenitis.[4] In each group studied, most patients suffered from sialadenitis in their twenties but there was also found to be a significant number of females whose symptoms started in their thirties and forties.[4] More women reported symptoms that were confirmed to be sialadenitis than men in this study, which may suggest that females are more likely to be affected but more research would need to be done to be sure of this.[4] A study done on the epidemiology of sialadenitis in the United States of America found that acute suppurative parotitis is responsible for 0.01-0.02% of hospital admissions, with the submandibular gland accounting for 10% of cases of sialadenitis in the major salivary glands in this population.[1] This study found that there was no predilection to any race, sex or age, although it was noted that sialadenitis in general tended to occur in people who are debilitated, dehydrated or older.[1] Bacterial sialadenitis is uncommon nowadays and is usually associated with sialoliths.[13] A study involving hospitals in the United Kingdom found that the incidence of admissions for sialadenitis is 27.5 per million of the population, with the most common cause being mumps which causes a viral infection in the salivary gland.[13] Ascending acute bacterial parotitis used to be a common perimortal event but today this is no longer the case due to antibiotics and basic modern care which means that patients will be much less likely to become dehydrated.[13] ## See also[edit] * Sialoendoscopy ## References[edit] 1. ^ a b c d e Yoskovitch, Adi (7 August 2018). "Submandibular Sialadenitis/Sialadenosis". Medscape eMedicine. Retrieved 4/12/2018. Check date values in: `\|access-date=` (help) 2. ^ M., Bruch, Jean (2010). Clinical oral medicine and pathology. Treister, Nathaniel S. New York: Humana Press. ISBN 9781603275200. OCLC 567351700. 3. ^ Mitchell, David; Mitchell, Laura (July 2014). Oxford Handbook of Clinical Dentistry. Oxford University Press. doi:10.1093/med/9780199679850.001.0001. ISBN 9780199679850. 4. ^ a b c d e f Avery, Chris (March 2018). "Sialadenitis". BMJ Best Practice. 5. ^ Harding, Dr Mary (18 December 2015). "Salivary Gland Disorders". patient.info. 6. ^ a b c d e f g h i j k "Sialadenitis - Causes - Clinical Features". TeachMeSurgery. Retrieved 2018-12-04. 7. ^ a b c Horsburgh, A.; Massoud, T. F. (January 2013). "The role of salivary duct morphology in the aetiology of sialadenitis: statistical analysis of sialographic features". International Journal of Oral and Maxillofacial Surgery. 42 (1): 124–128. doi:10.1016/j.ijom.2012.10.006. ISSN 1399-0020. PMID 23137733. 8. ^ a b c Isacsson, Göran; Lundquist, Per-G. (1982-08-01). "Salivary calculi as an aetiological factor in chronic sialadenitis of the submandibular gland". Clinical Otolaryngology and Allied Sciences. 7 (4): 231–236. doi:10.1111/j.1365-2273.1982.tb01389.x. ISSN 1365-2273. PMID 7127874. 9. ^ a b c d scholar.google.co.uk https://scholar.google.co.uk/scholar_url?url=http://www.academia.edu/download/46497427/j.1365-2559.1997.2530856.x20160614-21879-1oot9qv.pdf&hl=en&sa=X&scisig=AAGBfm1ZERo_kVpYCzthf7eLQwK49NNcYw&nossl=1&oi=scholarr. Retrieved 2018-12-04. Missing or empty `\|title=` (help) 10. ^ a b c d e Avery, C. (2018). Sialadenitis - Symptoms, diagnosis and treatment \| BMJ Best Practice. [online] Bestpractice.bmj.com. Available at: https://bestpractice.bmj.com/topics/en-gb/1038 [Accessed 2 Dec. 2018]. 11. ^ a b c d e f Tanakchi, S. (2018). Sialadenitis. [online] Pathologyoutlines.com. Available at: http://www.pathologyoutlines.com/topic/salivaryglandssialadenitis.html [Accessed 1 Dec. 2018]. 12. ^ a b c bestpractice.bmj.com > Sialadenitis Last updated: Sep 08, 2011 13. ^ a b c Cascarini, Luke; McGurk, Mark (August 2009). "Epidemiology of salivary gland infections". Oral and Maxillofacial Surgery Clinics of North America. 21 (3): 353–357. doi:10.1016/j.coms.2009.05.004. ISSN 1558-1365. PMID 19608052. ## External links[edit] Classification D * ICD-10: K11.2 * ICD-9-CM: 527.2 * MeSH: D012793 * v * t * e Oral and maxillofacial pathology Lips * Cheilitis * Actinic * Angular * Plasma cell * Cleft lip * Congenital lip pit * Eclabium * Herpes labialis * Macrocheilia * Microcheilia * Nasolabial cyst * Sun poisoning * Trumpeter's wart Tongue * Ankyloglossia * Black hairy tongue * Caviar tongue * Crenated tongue * Cunnilingus tongue * Fissured tongue * Foliate papillitis * Glossitis * Geographic tongue * Median rhomboid glossitis * Transient lingual papillitis * Glossoptosis * Hypoglossia * Lingual thyroid * Macroglossia * Microglossia * Rhabdomyoma Palate * Bednar's aphthae * Cleft palate * High-arched palate * Palatal cysts of the newborn * Inflammatory papillary hyperplasia * Stomatitis nicotina * Torus palatinus Oral mucosa – Lining of mouth * Amalgam tattoo * Angina bullosa haemorrhagica * Behçet's disease * Bohn's nodules * Burning mouth syndrome * Candidiasis * Condyloma acuminatum * Darier's disease * Epulis fissuratum * Erythema multiforme * Erythroplakia * Fibroma * Giant-cell * Focal epithelial hyperplasia * Fordyce spots * Hairy leukoplakia * Hand, foot and mouth disease * Hereditary benign intraepithelial dyskeratosis * Herpangina * Herpes zoster * Intraoral dental sinus * Leukoedema * Leukoplakia * Lichen planus * Linea alba * Lupus erythematosus * Melanocytic nevus * Melanocytic oral lesion * Molluscum contagiosum * Morsicatio buccarum * Oral cancer * Benign: Squamous cell papilloma * Keratoacanthoma * Malignant: Adenosquamous carcinoma * Basaloid squamous carcinoma * Mucosal melanoma * Spindle cell carcinoma * Squamous cell carcinoma * Verrucous carcinoma * Oral florid papillomatosis * Oral melanosis * Smoker's melanosis * Pemphigoid * Benign mucous membrane * Pemphigus * Plasmoacanthoma * Stomatitis * Aphthous * Denture-related * Herpetic * Smokeless tobacco keratosis * Submucous fibrosis * Ulceration * Riga–Fede disease * Verruca vulgaris * Verruciform xanthoma * White sponge nevus Teeth (pulp, dentin, enamel) * Amelogenesis imperfecta * Ankylosis * Anodontia * Caries * Early childhood caries * Concrescence * Failure of eruption of teeth * Dens evaginatus * Talon cusp * Dentin dysplasia * Dentin hypersensitivity * Dentinogenesis imperfecta * Dilaceration * Discoloration * Ectopic enamel * Enamel hypocalcification * Enamel hypoplasia * Turner's hypoplasia * Enamel pearl * Fluorosis * Fusion * Gemination * Hyperdontia * Hypodontia * Maxillary lateral incisor agenesis * Impaction * Wisdom tooth impaction * Macrodontia * Meth mouth * Microdontia * Odontogenic tumors * Keratocystic odontogenic tumour * Odontoma * Dens in dente * Open contact * Premature eruption * Neonatal teeth * Pulp calcification * Pulp stone * Pulp canal obliteration * Pulp necrosis * Pulp polyp * Pulpitis * Regional odontodysplasia * Resorption * Shovel-shaped incisors * Supernumerary root * Taurodontism * Trauma * Avulsion * Cracked tooth syndrome * Vertical root fracture * Occlusal * Tooth loss * Edentulism * Tooth wear * Abrasion * Abfraction * Acid erosion * Attrition Periodontium (gingiva, periodontal ligament, cementum, alveolus) – Gums and tooth-supporting structures * Cementicle * Cementoblastoma * Gigantiform * Cementoma * Eruption cyst * Epulis * Pyogenic granuloma * Congenital epulis * Gingival enlargement * Gingival cyst of the adult * Gingival cyst of the newborn * Gingivitis * Desquamative * Granulomatous * Plasma cell * Hereditary gingival fibromatosis * Hypercementosis * Hypocementosis * Linear gingival erythema * Necrotizing periodontal diseases * Acute necrotizing ulcerative gingivitis * Pericoronitis * Peri-implantitis * Periodontal abscess * Periodontal trauma * Periodontitis * Aggressive * As a manifestation of systemic disease * Chronic * Perio-endo lesion * Teething Periapical, mandibular and maxillary hard tissues – Bones of jaws * Agnathia * Alveolar osteitis * Buccal exostosis * Cherubism * Idiopathic osteosclerosis * Mandibular fracture * Microgenia * Micrognathia * Intraosseous cysts * Odontogenic: periapical * Dentigerous * Buccal bifurcation * Lateral periodontal * Globulomaxillary * Calcifying odontogenic * Glandular odontogenic * Non-odontogenic: Nasopalatine duct * Median mandibular * Median palatal * Traumatic bone * Osteoma * Osteomyelitis * Osteonecrosis * Bisphosphonate-associated * Neuralgia-inducing cavitational osteonecrosis * Osteoradionecrosis * Osteoporotic bone marrow defect * Paget's disease of bone * Periapical abscess * Phoenix abscess * Periapical periodontitis * Stafne defect * Torus mandibularis Temporomandibular joints, muscles of mastication and malocclusions – Jaw joints, chewing muscles and bite abnormalities * Bruxism * Condylar resorption * Mandibular dislocation * Malocclusion * Crossbite * Open bite * Overbite * Overeruption * Overjet * Prognathia * Retrognathia * Scissor bite * Maxillary hypoplasia * Temporomandibular joint dysfunction Salivary glands * Benign lymphoepithelial lesion * Ectopic salivary gland tissue * Frey's syndrome * HIV salivary gland disease * Necrotizing sialometaplasia * Mucocele * Ranula * Pneumoparotitis * Salivary duct stricture * Salivary gland aplasia * Salivary gland atresia * Salivary gland diverticulum * Salivary gland fistula * Salivary gland hyperplasia * Salivary gland hypoplasia * Salivary gland neoplasms * Benign: Basal cell adenoma * Canalicular adenoma * Ductal papilloma * Monomorphic adenoma * Myoepithelioma * Oncocytoma * Papillary cystadenoma lymphomatosum * Pleomorphic adenoma * Sebaceous adenoma * Malignant: Acinic cell carcinoma * Adenocarcinoma * Adenoid cystic carcinoma * Carcinoma ex pleomorphic adenoma * Lymphoma * Mucoepidermoid carcinoma * Sclerosing polycystic adenosis * Sialadenitis * Parotitis * Chronic sclerosing sialadenitis * Sialectasis * Sialocele * Sialodochitis * Sialosis * Sialolithiasis * Sjögren's syndrome Orofacial soft tissues – Soft tissues around the mouth * Actinomycosis * Angioedema * Basal cell carcinoma * Cutaneous sinus of dental origin * Cystic hygroma * Gnathophyma * Ludwig's angina * Macrostomia * Melkersson–Rosenthal syndrome * Microstomia * Noma * Oral Crohn's disease * Orofacial granulomatosis * Perioral dermatitis * Pyostomatitis vegetans Other * Eagle syndrome * Hemifacial hypertrophy * Facial hemiatrophy * Oral manifestations of systemic disease [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Sialadenitis	c0037023	25,648	wikipedia	https://en.wikipedia.org/wiki/Sialadenitis	2021-01-18T18:53:50	{"gard": ["7638"], "mesh": ["D012793"], "umls": ["C0037023"], "wikidata": ["Q2002586"]}
Monument for the unborn child on a main road between Mosta and Naxxar The de jure legal status of abortion in Malta holds that the practice is illegal. Malta is the only country in the European Union to prohibit abortion entirely.[1] Abortion for an ectopic pregnancy is allowed with a case-by-case decision.[2] ## Contents * 1 Criminal code * 2 Overview * 3 See also * 4 References ## Criminal code[edit] The Criminal Code states:[3] "(1) Whosoever, by any food, drink, medicine, or by violence, or by any other means whatsoever, shall cause the miscarriage of any woman with child, whether the woman be consenting or not, shall, on conviction, be liable to imprisonment for a term from 18 months to three years"; and "(2) The same punishment shall be awarded against any woman who shall procure her own miscarriage, or who shall have consented to the use of the means by which the miscarriage is procured." In 2005 Tonio Borg, a Maltese politician, sought to amend the constitution to completely ban abortion.[4] ## Overview[edit] It is estimated that anywhere between 300 and 400 Maltese women travel abroad to have abortions each year, mostly to the UK (about 60 per year) and Italy, with Germany, the Netherlands, and Belgium being some of the other destinations as well.[5] This estimate means that Maltese women have abortions about as often as the EU average, despite Malta being the only EU country which bans the procedure (the rate for Malta is between 3.6 and 4.7 per thousand women; the EU average is 4.4).[5] ## See also[edit] * Abortion in Poland * Abortion in Ireland * Abortion in Northern Ireland ## References[edit] 1. ^ "Malta now only EU country apart from Northern Ireland without life-saving abortion law". Malta Independent. Retrieved 6 September 2014. 2. ^ https://timesofmalta.com/articles/view/doctors-praise-protocol-for-ectopic-pregnancies-after-womans-claims.835877 3. ^ "What does the law actually say?". Malta Humanist Association. Retrieved November 12, 2016. 4. ^ "Plans for abortion law to be entrenched in Constitution". Times of Malta. May 7, 2005. 5. ^ a b "300 to 400 Maltese Women Go Abroad For An Abortion Each Year". Times of Malta. February 4, 2018. * v * t * e Abortion in Europe Sovereign states * Albania * Andorra * Armenia * Austria * Azerbaijan * Belarus * Belgium * Bosnia and Herzegovina * Bulgaria * Croatia * Cyprus * Czech Republic * Denmark * Estonia * Finland * France * Georgia * Germany * Greece * Hungary * Iceland * Ireland * * Italy * Kazakhstan * Latvia * Liechtenstein * Lithuania * Luxembourg * Malta * Moldova * Monaco * Montenegro * Netherlands * North Macedonia * Norway * Poland * Portugal * Romania * Russia * San Marino * Serbia * Slovakia * Slovenia * Spain * Sweden * Switzerland * Turkey * Ukraine * United Kingdom * England * Northern Ireland * Scotland * Wales * Vatican City States with limited recognition * Abkhazia * Artsakh * Kosovo * Northern Cyprus * South Ossetia * Transnistria * v * t * e Abortion Main topics * Definitions * History * Methods * Abortion debate * Philosophical aspects * Abortion law Movements * Abortion-rights movements * Anti-abortion movements Issues * Abortion and mental health * Beginning of human personhood * Beginning of pregnancy controversy * Abortion-breast cancer hypothesis * Anti-abortion violence * Abortion under communism * Birth control * Crisis pregnancy center * Ethical aspects of abortion * Eugenics * Fetal rights * Forced abortion * Genetics and abortion * Late-term abortion * Legalized abortion and crime effect * Libertarian perspectives on abortion * Limit of viability * Malthusianism * Men's rights * Minors and abortion * Natalism * One-child policy * Paternal rights and abortion * Prenatal development * Reproductive rights * Self-induced abortion * Sex-selective abortion * Sidewalk counseling * Societal attitudes towards abortion * Socialism * Toxic abortion * Unsafe abortion * Women's rights By country Africa * Algeria * Angola * Benin * Botswana * Burkina Faso * Burundi * Cameroon * Cape Verde * Central African Republic * Chad * Egypt * Ghana * Kenya * Namibia * Nigeria * South Africa * Uganda * Zimbabwe Asia * Afghanistan * Armenia * Azerbaijan * Bahrain * Bangladesh * Bhutan * Brunei * Cambodia * China * Cyprus * East Timor * Georgia * India * Iran * Israel * Japan * Kazakhstan * South Korea * Malaysia * Nepal * Northern Cyprus * Philippines * Qatar * Saudi Arabia * Singapore * Turkey * United Arab Emirates * Vietnam * Yemen Europe * Albania * Andorra * Austria * Belarus * Belgium * Bosnia and Herzegovina * Bulgaria * Croatia * Czech Republic * Denmark * Estonia * Finland * France * Germany * Greece * Hungary * Iceland * Ireland * Italy * Kazakhstan * Latvia * Liechtenstein * Lithuania * Luxembourg * Malta * Moldova * Monaco * Montenegro * Netherlands * North Macedonia * Norway * Poland * Portugal * Romania * Russia * San Marino * Serbia * Slovakia * Slovenia * Spain * Sweden * Switzerland * Ukraine * United Kingdom North America * Belize * Canada * Costa Rica * Cuba * Dominican Republic * El Salvador * Guatemala * Mexico * Nicaragua * Panama * Trinidad and Tobago * United States Oceania * Australia * Micronesia * Fiji * Kiribati * Marshall Islands * New Zealand * Papua New Guinea * Samoa * Solomon Islands * Tonga * Tuvalu * Vanuatu South America * Argentina * Bolivia * Brazil * Chile * Colombia * Ecuador * Guyana * Paraguay * Peru * Suriname * Uruguay * Venezuela Law * Case law * Constitutional law * History of abortion law * Laws by country * Buffer zones * Conscientious objection * Fetal protection * Heartbeat bills * Informed consent * Late-term restrictions * Parental involvement * Spousal consent Methods * Vacuum aspiration * Dilation and evacuation * Dilation and curettage * Intact D&X * Hysterotomy * Instillation * Menstrual extraction * Abortifacient drugs * Methotrexate * Mifepristone * Misoprostol * Oxytocin * Self-induced abortion * Unsafe abortion Religion * Buddhism * Christianity * Catholicism * Hinduism * Islam * Judaism * Scientology * Category This Malta-related article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Abortion in Malta	None	25,649	wikipedia	https://en.wikipedia.org/wiki/Abortion_in_Malta	2021-01-18T18:34:31	{"wikidata": ["Q737326"]}
A number sign (#) is used with this entry because susceptibility to systemic lupus erythematosus is influenced by a haplotype of the CR2 gene (120650). For a phenotypic description and a discussion of genetic heterogeneity of systemic lupus erythematosus (SLE), see 152700. Mapping Wu et al. (2007) found evidence of linkage at chromosome 1q32.2 in a targeted genome scan of chromosome 1q21-q43 in 126 SLE multiplex families containing 151 affected sib pairs (nonparametric linkage score of 2.52; p = 0.006). The authors analyzed the CR2 gene (120650) in 1,416 individuals from 258 Caucasian and 142 Chinese SLE simplex families and demonstrated that a common 3-SNP haplotype (120650.0001) was associated with SLE susceptibility (p = 0.00001) with a 1.54-fold increased risk for development of disease. Wu et al. (2007) concluded that the CR2 gene is likely a susceptibility gene for SLE. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	SYSTEMIC LUPUS ERYTHEMATOSUS, SUSCEPTIBILITY TO, 9	c1970455	25,650	omim	https://www.omim.org/entry/610927	2019-09-22T16:03:54	{"omim": ["610927"]}
## Summary ### Clinical characteristics. Silver-Russell Syndrome (SRS) is typically characterized by asymmetric gestational growth restriction resulting in affected individuals being born small for gestational age, with relative macrocephaly at birth (head circumference ≥1.5 SD above birth weight and/or length), prominent forehead usually with frontal bossing, and frequently body asymmetry. This is followed by postnatal growth failure, and in some cases progressive limb length discrepancy and feeding difficulties. Additional clinical features include triangular facies, fifth-finger clinodactyly, and micrognathia with narrow chin. Except for the limb length asymmetry, the growth failure is proportionate and head growth normal. The average adult height in untreated individuals is ~3.1±1.4 SD below the mean. The Netchine-Harbison Clinical Scoring System (NH-CSS) is a sensitive diagnostic scoring system. Clinical diagnosis can be established in an individual who meets at least four of the NH-CSS clinical criteria – prominent forehead/frontal bossing and relative macrocephaly at birth plus two additional findings – and in whom other disorders have been ruled out. ### Diagnosis/testing. SRS is a genetically heterogeneous condition. Genetic testing confirms clinical diagnosis in approximately 60% of affected individuals. Hypomethylation of the imprinted control region 1 (ICR1) at 11p15.5 causes SRS in 35%-50% of individuals, and maternal uniparental disomy (mUPD7) causes SRS in 7%-10% of individuals. There are a small number of individuals with SRS who have duplications, deletions or translocations involving the imprinting centers at 11p15.5 or duplications, deletions, or translocations involving chromosome 7. Rarely, affected individuals with pathogenic variants in CDKN1C, IGF2, PLAG1, and HMGA2 have been described. However, approximately 40% of individuals who meet NH-CSS clinical criteria for SRS have negative molecular and/or cytogenetic testing. ### Management. Treatment of manifestations: Multidisciplinary follow up and early, specific intervention are necessary for optimal management of affected individuals. Treatment may include growth hormone therapy. Hypoglycemia should be prevented or aggressively managed. Strategies for feeding disorders include nutritional and caloric supplements, medication for gastroesophageal reflux, therapy for oral motor problems and feeding aversion, cyproheptadine for appetite stimulation, and enteral tube feeding as needed. Lower-limb length discrepancy exceeding 2 cm requires intervention. In older children, distraction osteogenesis is recommended for most individuals. Physical, occupational, speech, and language therapy with an individualized education plan are used to treat delays. Psychological counseling can be used as needed to address psychosocial and body image issues. Severe micrognathia or cleft palate should be managed by a multidisciplinary craniofacial team. Males with cryptorchidism or hypospadias should be referred to a urologist. Males with micropenis and females with internal genitourinary anomalies benefit from referral to a multidisciplinary disorders of sex development center. Surveillance: Monitoring of: growth velocity; blood glucose concentration and urine ketones for hypoglycemia in infants and as needed in older children; limb length at each well-child visit in early childhood for evidence of asymmetric growth; evaluation for scoliosis, signs of premature central puberty, dental crowding and malocclusion, and speech/language development. Agents/circumstances to avoid: prolonged fasting in infants and young children because of the risk for hypoglycemia; elective surgery whenever possible due to risk of hypoglycemia, hypothermia, difficult healing, and difficult intubation. ### Genetic counseling. SRS has multiple etiologies and typically has a low recurrence risk. In most families, a proband with Silver-Russell syndrome (SRS) represents a simplex case (a single affected family member) and has SRS as the result of an apparent de novo epigenetic or genetic alteration (e.g., loss of paternal methylation at the 11p15 ICR1 H19/IGF2 imprinting center 1 or maternal uniparental disomy for chromosome 7). SRS may also occur as the result of a genetic alteration associated with up to a 50% recurrence risk (e.g., a copy number variant on chromosome 7 or 11 or an intragenic pathogenic variant in CDKN1C, IGF2, PLAG2, or HMGA2) depending on the nature of the genetic alteration and the gender of the transmitting parent. Accurate assessment of SRS recurrence therefore requires identification of the causative genetic mechanism in the proband. ## Diagnosis Silver-Russell syndrome (SRS) is a genetically heterogeneous disorder; the clinical diagnosis requires fulfillment of specific clinical criteria described in the Netchine-Harbison clinical scoring system (NH-CSS) listed in Suggestive Findings [Azzi et al 2015]. This scoring system has been accepted as the method for identifying those individuals who should have further evaluation for diagnosis of SRS [Wakeling et al 2017]. ### Suggestive Findings Silver-Russell syndrome (SRS) should be suspected in individuals who meet the NH-CSS clinical criteria [Azzi et al 2015] as follows: * Small for gestational age (birth weight and/or length ≥2 SD below the mean for gestational age) * Postnatal growth failure (length/height ≥ SD below the mean at 24 months) * Relative macrocephaly at birth (head circumference >1.5 SD above birth weight and/or length) * Frontal bossing or prominent forehead (forehead projecting beyond the facial plane on a side view as a toddler [1–3 years]) * Body asymmetry (limb length discrepancy ≥0.5 cm, or <0.5 cm with ≥2 other asymmetric body parts) * Feeding difficulties or body mass index ≤2 SD at 24 months or current use of a feeding tube or cyproheptadine for appetite stimulation If an individual meets four of the six criteria, the clinical diagnosis is suspected and molecular confirmation testing is warranted. Some rare individuals meeting three of the six criteria have had a positive molecular confirmation for SRS. ### Establishing the Diagnosis The diagnosis of SRS is established in a proband who meets four of the six Netchine-Harbison clinical diagnostic criteria and who has findings on molecular genetic testing consistent with either hypomethylation on chromosome 11p15.5 or maternal uniparental disomy (UPD) for chromosome 7 (see Table 1). Chromosome 11p15.5 imprinting cluster. SRS is associated with abnormal regulation of gene transcription in two imprinted domains on chromosome 11p15.5. Regulation may be disrupted by any one of numerous mechanisms. See Molecular Pathogenesis for a detailed description of the regulation of gene expression in this region. Maternal UPD7 can occur by different mechanisms. See Molecular Pathogenesis. An algorithm for investigation of the diagnosis of SRS was published by the International Expert Consensus [Wakeling et al 2017]. See Figure 1. #### Figure 1. Flow chart for investigation and diagnosis of Silver-Russell Syndrome This figure was adapted (legends not included) from Wakeling et al [2017], which was published under a Creative Commons Attribution 4.0 International License. The recommended order of testing for SRS is the following: * Methylation analysis of 11p15.5 ICR1/ICR2 and maternal UPD7 studies may be ordered simultaneously. Note: (1) Detection of an abnormality is dependent on the mechanism of disease and methodology used (see Table 1). (2) Mosaicism has been reported; therefore, testing of other tissues (e.g., buccal cells or skin fibroblasts) may be considered if leukocyte testing is normal. * If methylation analysis of 11p15.5 ICR1/ICR2 and maternal UPD7 studies are normal, sequence analysis of IGF2, CDKN1C, PLAG1, and HMGA2 may be considered. Note: Some individuals ultimately diagnosed with SRS will have a SNP chromosomal microarray (CMA) based on their significant growth restriction noted at birth or later based on speech or other developmental delays. While this is not a first-tier testing recommendation for someone suspected of having SRS, it can uncover chromosome 7 or 11 abnormalities that establish the diagnosis (see Table 1). If methylation analysis of 11p15.5 ICR1/ICR2 and UPD7 studies are normal, a multigene panel that includes sequence analysis of IGF2, CDKN1C, PLAG1, HMGA2, 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 is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. #### Note Approximately 40% of individuals who undergo molecular testing after scoring four of six on the Netchine-Harbison scoring system will have nondiagnostic laboratory studies. For individuals in this group, a clinical diagnosis of SRS can be established if: (a) two of the four clinical findings identified are prominent forehead/frontal bossing and relative macrocephaly at birth; and (b) other disorders have been ruled out [Wakeling et al 2017] (see Differential Diagnosis). ### Table 1. Molecular Genetic Testing Used in Russell-Silver Syndrome View in own window MethodPathogenic Variants/Alterations DetectedProportion of SRS Alterations Detected 1 Methylation analysis 2Chr11Loss of methylation at H19/IGF2 (paternal) 3~35%-50% 4 Somatic mosaicism for maternal UPD11 5, 6Rare Duplication of 11p15.5 (maternal)Unknown 7, 8 Chr7Maternal UPD7 9~7%-10% 10 Microdeletions, microduplications, mosaic trisomy 7Rare 11 Microarray (SNP based)Chr11Duplication of 11p15.5 (maternal)Unknown 7, 8 Somatic mosaicism for maternal UPD11 5, 6Rare 12 Chr7Microdeletions or microduplications of 7p, mosaic trisomy 7Rare 11, 13, 14 Maternal UPD7Maternal isodisomy 7 only 15 STR marker analysisChr11Somatic mosaicism for maternal UPD11 5, 6Rare Chr7Maternal UPD7 9~7%-10% 10 KaryotypeInversion or translocation of 11p15.5Rare 5, 6 Sequence analysis 16 / gene-targeted deletion/ duplication analysis 17CDKN1C (maternal transmission)1 family reported 18 IGF2 (paternal transmission)A few cases reported 19 PLAG1Rare 20 HMGA2Rare 21 Unknown30%-40% 22 1\. See Molecular Genetics for information on variants/alterations detected. 2\. Assays developed to be methylation sensitive such as multiplex ligation probe analysis (MS-MLPA), quantitative PCR (MS-qPCR), or Southern blotting (mainly historic testing) allow detection of epigenetic and genomic alterations of 11p15.5. Methylation-sensitive assays can diagnose RSS resulting from DNA methylation alterations, microdeletions and microduplications, or uniparental disomy (UPD). Interpretation of methylation data should take into account results of copy number testing because copy number variants that alter the relative dosage of parental contributions (e.g., paternal duplication) are associated with abnormal methylation status. Note that MLPA testing may be followed by microarray testing to define breakpoints of deletions or duplications. Other methods to confirm maternal UPD at 11p15.5 include short tandem repeat (STR) analysis or SNP analysis [Keren et al 2013]. 3\. A small number of individuals have hypothmethylation of only H19 or IGF2 [Bartholdi et al 2009]. 4\. False negatives may occur as a result of mosaicism, as 11p15.5 hypomethylation occurs post fertilization. Testing of tissue from a second source (e.g., buccal cells or fibroblasts) should be performed. 5\. Bullman et al [2008] 6\. Luk et al [2016a] 7\. Fisher et al [2002], Eggermann et al [2005], Schönherr et al [2007] 8\. Heide et al [2018] 9\. Both isodisomy and heterodisomy [Bernard et al 1999, Price et al 1999] as well as segmental maternal UPD [Hannula et al 2001, Eggermann 2008] have been reported. Mosaicism has been observed in cases of maternal UPD7 and other chromosome 7 rearrangements; therefore, testing of an alternate tissue source may be appropriate [Reboul et al 2006]. 10\. Hannula et al [2001], Kim et al [2005] 11\. Courtens et al [2005], Flori et al [2005], Font-Montgomery et al [2005] 12\. Luk et al [2016b] described one group of 28 individuals with SRS who had UPD11. 13\. A de novo duplication of 7p11.2-p13 on the maternal allele containing GRB10, GFBP1, and GFBP3 has been reported [Monk et al 2000]. 14\. A de novo deletion of 7q32.2 on the paternal allele including MEST has been reported [Carrera et al 2016]. 15\. Note: SNP array analysis will detect maternal UPD only in cases of isodisomy; 28.8% of maternal UPD7 (2%-3% of all cases of SRS) are a result of isodisomy [Chantot-Bastaraud et al 2017]. 16\. 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, partial-, whole-, or multigene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 17\. 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. 18\. One four-generation family segregating a CDKN1C gain-of-function variant has been described [Brioude et al 2013]. 19\. One family with SRS and a paternally transmitted IGF2 loss-of-function variant has been reported by Begemann et al [2015] and a few others have been reviewed by Tümer et al [2018]. 20\. Loss-of-function PLAG1 variants where identified in two familial and one simplex case [Abi Habib et al 2018]. 21\. Loss-of-function HMGA2 variants were identified in two simplex cases [Abi Habib et al 2018]. 22\. Approximately 40% of individuals who undergo molecular testing after scoring four of six on the Netchine-Harbison scoring system will have nondiagnostic laboratory studies. See Note. ## Clinical Characteristics ### Clinical Description Silver-Russell Syndrome (SRS) is typically characterized by asymmetric gestational growth restriction resulting in affected individuals being born small for gestational age with relative macrocephaly at birth (head circumference ≥1.5 SD above birth weight and/or length), prominent forehead usually with frontal bossing, and frequently body asymmetry. This is followed by postnatal growth failure, and in some cases progressive limb length discrepancy and severe feeding difficulties in the first years of life. Additional clinical features include triangular facies, fifth-finger clinodactyly, and micrognathia with narrow chin. Except for the limb length asymmetry, the growth failure is proportionate with normal head growth. The average adult height in untreated individuals is ~3.1±1.4 SD below the mean. SRS is an etiologically heterogeneous condition. In the recent international consensus statement for diagnosis and management of SRS [Wakeling et al 2017], the Netchine-Harbison Clinical Scoring System [Netchine et al 2007, Azzi et al 2015] was selected as the most sensitive of the compared diagnostic scoring systems. Netchine-Harbison Clinical Scoring System (NH-CSS) [Azzi et al 2015]: * Small for gestational age (birth weight and/or length ≤2 SD for gestational age) * Postnatal growth failure (length/height ≥2 SD below the mean at 24 months) * Relative macrocephaly at birth (head circumference >1.5 SD above birth weight and/or length) * Frontal bossing or prominent forehead (Forehead projecting beyond the facial plane on a side view as a toddler [1–3 years]) * Body asymmetry (limb length discrepancy ≥0.5 cm, or <0.5 cm with ≥2 other asymmetric body parts) * Feeding difficulties or BMI ≤2 SD at 24 months or current use of a feeding tube or cyproheptadine for appetite stimulation Clinical diagnosis is made when an infant meets at least four of the clinical criteria, two of which must be relative macrocephaly at birth and frontal bossing. In older children and adults, the facial features can evolve and the prominent forehead can disappear. Therefore, in order to be able to use the NH-CSS in older children and adults, the prominence of the forehead needs to be assessed in childhood and profile photographs taken of the individual at around age two years. Individuals with SRS typically have additional supportive clinical findings, including the following: * Delayed closure of anterior fontanelle * Triangular face * Micrognathia * Dental crowding * Down-turned corners of the mouth * High pitched voice * Diminished muscle mass * Shoulder dimples * Hypoplastic elbow joints * Fifth-finger clinodactyly and/or brachydactyly * Scoliosis * Excessive sweating * Fasting hypoglycemia * Speech delay * Motor delay * Genitourinary anomalies Growth. The earliest manifestation of SRS is abnormal growth. Most children are born small for gestational age with birth weight and/or length ≥2 SD below the mean. Although growth velocity may be within the normal range, children with SRS rarely show significant catch-up growth. At age two years, most children with SRS remain >2 SD below the mean for length unless the parents are tall. Growth charts for European children with SRS have been published [Wollmann et al 1995]. Growth charts for North American children with the Wollmann data superimposed are available from the MAGIC Foundation (accessed 5-22-20). In two European series of untreated adults with SRS, height ranged from 3.7 to 3.5 SD below the mean for males and 4.2 to 2.5 SD below the mean for females [Wollmann et al 1995, Binder et al 2013]. Except for the limb length asymmetry, the growth failure is proportionate, with normal head growth. Most children diagnosed clinically as having SRS who demonstrated catch-up growth in later childhood had conditions other than classic SRS [Saal et al 1985]. See Management for use of growth hormone therapy to influence growth in children with SRS. Note: Many children with SRS do not achieve normal stature even with administration of human growth hormone if rapid bone age advancement during puberty is not managed. Other endocrinologic issues can include premature adrenarche, early puberty, and insulin resistance, which can contribute to a reduced final height even after treatment with growth hormone. Skeletal abnormalities may include: * Limb length asymmetry, caused by hemihypotrophy with diminished growth of the affected side; * Fifth-finger clinodactyly and/or brachydactyly, among the most frequently described skeletal anomalies (albeit minor) in individuals with SRS; * Scoliosis, which has been reported in some studies in up to 36% of individuals with SRS [Abraham et al 2004]. A more recent study identified scoliosis or kyphosis in 21% of individuals; 18% required corrective surgery [Yamaguchi et al 2015]. Neurodevelopment. Besides the growth issues, neurodevelopment is of great concern to parents. Evidence shows that children with this condition are at increased risk for developmental delay (both motor and cognitive) and learning disabilities. In a review of a large cohort of children with SRS with either 11p15 methylation defects or maternal UPD7, developmental delay was seen in 34% of individuals, the majority of whom had mild delays. Developmental delays were more commonly seen in those with maternal UPD7 than in those with 11p15 methylation defects (65% vs 20%). Speech delays were common in both groups [Wakeling et al 2010]. Further studies of individuals with molecularly confirmed SRS and early appropriate clinical management are needed to give a more accurate cognitive prognosis. Feeding disorders and hypoglycemia. Children with SRS have little subcutaneous fat and often have poor appetites, oral motor problems, and feeding disorders [Fuke et al 2013]. They are at risk for hypoglycemia, especially associated with any prolonged fast [Wakeling et al 2017]. In a study of children with SRS, contributing factors for hypoglycemia included reduced caloric intake, often secondary to poor appetite and feeding; reduced body mass; and, in several children, growth hormone deficiency [Azcona & Stanhope 2005]. While most children had clinical symptoms of hypoglycemia, several were asymptomatic. Diaphoresis in early childhood may be associated with hypoglycemia, although diaphoresis may often occur in the absence of hypoglycemia in children with SRS [Stanhope et al 1998]. Gastrointestinal disorders are common and problems include gastroesophageal reflux disease, esophagitis, food aversion, vomiting, constipation and failure to thrive. One large study documented gastrointestinal problems in 77% of children, and 55% of children had severe gastroesophageal reflux, which may have an atypical presentation without vomiting in this group of children [Marsaud et al 2015]. Reflux esophagitis should be suspected in children with either food aversion or aspiration. Craniofacial anomalies are common. Some individuals with SRS have Pierre Robin sequence and cleft palate. Within a group of individuals with SRS, Wakeling et al [2010] found cleft palate or bifid uvula in 7% of those with 11p15.5 methylation defects and in no individuals with maternal UPD7. Those individuals with Pierre Robin sequence should be monitored for obstructive apnea. Dental and oral abnormalities are common. Microdontia, high-arched palate, and dental crowding secondary to the relative micrognathia and small mouth have been reported [Orbak et al 2005, Wakeling et al 2010]. Overbite and dental crowding appear to be the most common orofacial manifestation [Hodge et al 2015] Poor oral hygiene in the presence of dental crowding can lead to increased risk for dental caries. Genitourinary problems have been observed. The most common anomalies are hypospadias and cryptorchidism in males [Bruce et al 2009, Wakeling et al 2017]. Mayer-Rokitansky-Kuster-Hauser syndrome (associated with underdeveloped or absent vagina and uterus with normal appearance of the external genitalia) has been reported in females [Bruce et al 2009, Abraham et al 2015]. Renal anomalies are not common; however, horseshoe kidney and renal dysplasia have been reported [Wakeling et al 2010]. Heart defects are uncommon, but have been reported in larger studies [Wakeling et al 2010] and smaller case series [Ghanim et al 2013]. The prevalence of heart defects may be as high as 5.5% [Ghanim et al 2013]. ### Genotype-Phenotype Correlations Using methylation-sensitive restriction enzymes HpaII or NotI to measure the degree of methylation of H19, Bruce et al [2009] developed a scale of extreme H19 hypomethylation, moderate H19 hypomethylation, normal H19 methylation, and maternal UPD7 (normal H19 methylation). They determined that children with SRS with extreme H19 hypomethylation (i.e., ≥6 SD below the mean or <9% methylation) were more likely to have more severe skeletal manifestations (including radiohumeral dislocation, syndactyly, greater limb asymmetry, and scoliosis) than children with SRS with moderate hypomethylation and those with maternal UPD7. A study by Wakeling et al [2010] compared clinical features of children with SRS caused by 11p15.5 ICR1 IGF2/H19 methylation defects to those with maternal UPD7. They found fifth-finger clinodactyly and congenital anomalies were more frequent in children with 11p 15.5 ICR1 hypomethylation than in those with maternal UPD7, whereas learning difficulties and speech disorders were more frequent in children with maternal UPD7 than in those with ICR1 hypomethylation. Children with SRS with maternal UPD7 had more gain in height with growth hormone therapy compared to children with 11p15.5 epimutations, possibly because children with 11p15.5 methylation abnormalities showed elevated levels of insulin-like growth factor I (product of IGF1) and therefore a degree of IGF1 resistance; children with SRS with maternal UPD7 had response characteristics similar to other children who were small for gestational age [Binder et al 2008]. ### Prevalence The prevalence is unknown and was previously estimated at 1:30,000-1:100,000 (A Toutain, Orphanet). A recent retrospective study conducted in Estonia estimated the minimum prevalence of SRS at birth as 1:15,886 [Yakoreva et al 2019]. ## Differential Diagnosis Intrauterine growth restriction and short stature. The differential diagnosis of Silver-Russell syndrome (SRS) includes any condition that can cause intrauterine growth restriction and short stature. The presence of disproportionate short stature excludes the diagnosis of SRS and suggests a diagnosis of skeletal dysplasia. A skeletal survey can be performed to exclude a skeletal dysplasia that may mimic SRS. Note: Bone age may be delayed in children with SRS; however, delayed bone age is a nonspecific finding frequently seen in children with intrauterine growth restriction of many etiologies. Chromosome abnormalities. Many conditions caused by a chromosome imbalance can be associated with small size for gestational age and poor postnatal growth, leading to a misdiagnosis of SRS. Chromosome microarray, preferably using a SNP-based platform, can be helpful for identifying microdeletions and microduplications as well as regions of homozygosity, giving potential clues to uniparental chromosomal disomy, and rare recessive disorders in the cases of consanguinity [Grote et al 2014]. Uniparental disomy for several chromosomes have been reported to cause an SRS-like phenotype, including chromosomes 6, 14 (Temple syndrome), 16, and 20 [Sachwitz et al 2016, Wakeling et al 2017, Geoffron et al 2018]. Microcephaly. Individuals with SRS have a normal head circumference or relative macrocephaly. The presence of a significant microcephaly should lead to a search for an alternative etiology. Table 3 summarizes disorders to consider in the differential diagnosis of Silver-Russell syndrome. ### Table 3. Other Disorders with IUGR and Poor Postnatal Growth to Consider in the Differential Diagnosis of Silver-Russell Syndrome View in own window DisorderGene(s)MOIAdditional Clinical Features of This Disorder Overlapping w/SRSDistinguishing from SRS Monogenic disordersThree M syndromeCCDC8 CUL7 OBSL1AR * Clinodactyly * Frontal bossing * Relative macrocephaly * Triangular facies * Pectus excavatum * Rib hypoplasia * Short neck IMAGe syndromeCDKN1CAD 1 * Frontal bossing * Macrocephaly * Adrenal hypoplasia * Adrenal insufficiency * Metaphyseal dysplasia Bloom syndromeBLMAR * Triangular facies * 5th-finger clinodactly * Café au lait spots * Abnormal sister chromatid exchange * Dolichocephaly * Microcephaly Nijmegen breakage syndromeNBNARCafé au lait spots * Chr instability * Microcephaly * Sloping forehead * Telangiectasia Warsaw breakage syndrome (OMIM 613398)DDX11AR5th-finger clinodactyly * Chr instability * Deafness * Microcephaly * Sloping forehead * Epicanthal folds Fanconi anemia>20 genes 2AR AD XLCafé au lait spots * Chr instability * Absent thumb(s) or thumb hypoplasia * Microcephaly * Radial anomalies * ↑ malignancy risk Meier-Gorlin syndrome (OMIM 224690)CDC45 CDC6 CDT1 GMNN MCM5 ORC1 ORC4 ORC6AR ADFrontal bossing * Absent patellae * Microcephaly * Microtia * Small mouth Insulin growth factor 1 resistance (incl deletion 15q26.1) 3IGF1RAR AD * Clinodactyly * Dental anomalies * Global DD * Microcephaly * Synophrys Chromosome abnormalitiesDiploiod/triploid mixoploidy 4Limb asymmetry * Global DD * Microcephaly Temple syndrome (maternal UPD14, paternal chr 14 deletion or loss of methylation at 14q32) (OMIM 616222)Many features overlap w/SRS. * Distinguished by genetic testing 5 * Similar phenotype Teratogenic disorderFetal alcohol syndrome * Small for gestational age * Postnatal growth failure * 5th-finger clinodactyly * Microcephaly * Hypoplastic philtrum * History of in utero exposure to alcohol * Short palpebral fissures AD = autosomal dominant; AR = autosomal recessive; Chr = chromosome; DD = developmental delay; IUGR = intrauterine growth restriction; MOI = mode of inheritance; XL = X-linked 1\. Typically a CDKN1C pathogenic variant causing IMAGe syndrome is inherited in an autosomal dominant manner; however, only maternal transmission of the pathogenic variant results in IMAGe syndrome. 2\. Fanconi anemia is associated with pathogenic variants involving BRCA2, BRIP1, ERCC4, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, MAD2L2, PALB2, RAD51, RAD51C, RFWD3, SLX4, UBE2T, or XRCC2. 3\. Bruce et al [2009], Ocaranza et al [2017] 4\. Graham et al [1981] 5\. Ioannides et al [2014], Kagami et al [2015], Geoffron et al [2018] ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease in an individual diagnosed with Silver-Russell syndrome (SRS), the following evaluations are recommended if they have not already been completed: * Assessment and plotting of growth curves. See the MAGIC Foundation. * Physical examination for evaluation of possible limb length asymmetry, genitourinary anomalies, scoliosis, precocious or early-onset puberty, and oral and craniofacial abnormalities * Consultation with a pediatric endocrinologist * Consultation with a pediatric gastroenterologist and dietician * For children suspected of having gastroesophageal reflux disease (GERD), evaluation for esophagitis including video swallow studies, gastric emptying studies pH probe, and endoscopy. * Intestinal malrotation has been reported in children with SRS and needs to be ruled out in those who have feeding disorders, constipation and delayed gastric emptying. * Screening assessment of neurocognitive development, speech and language, and muscle tone * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations SRS leads to a wide spectrum of abnormal physical characteristics and functional abnormalities. Multidisciplinary follow up and early, specific, interventions are necessary for optimal management of individuals with SRS. The multidisciplinary team should be composed of pediatric subspecialists including an endocrinologist, gastroenterologist, dietician, clinical geneticist and genetic counselor, craniofacial team, orthopedic surgeon, neurologist, speech and language therapist, and psychologist Growth and use of growth hormone. Children with any condition associated with body differences and/or short stature are often sensitive about body image. These factors can play a significant role in self-image, peer relationships, and socialization. Thus, early referral to a pediatric endocrinologist is essential for children with SRS. * Growth hormone therapy in children with intrauterine growth restriction of all causes has significantly improved growth and final height, especially in those children who do not experience catch-up growth [Dahlgren et al 2005, Jensen et al 2014, Zanelli & Rogol 2018]. Specifically, children with SRS have benefited from growth hormone supplementation [Toumba et al 2010, Binder et al 2013]. * Smeets et al [2016] found that height gain in children with SRS treated with growth hormone was similar to that in children who did not have SRS, although final heights were less in the SRS population because their heights were lower at the initiation of treatment [Smeets et al 2016]. * The goals of GH treatment are, of course, to improve growth velocity but also to improve body composition (especially lean body mass), psychomotor development, and appetite; to reduce the risk of hypoglycaemia; and to optimize linear growth [Wakeling et al 2017]. * A study by Rizzo et al [2001] demonstrated significant increase in height in children with SRS treated with growth hormone, but without a change in body or limb asymmetry * Such treatment is best undertaken in a center with experience in managing growth disorders. * Growth hormone deficiency. Treatment with human growth hormone is necessary in the presence of documented growth hormone deficiency. However, growth hormone deficiency is not common in SRS [Wakeling et al 2017]. * Treatment with growth hormone in SRS is indicated and not altered even in the presence of growth hormone deficiency. * Testing for growth hormone deficiency by fasting is contraindicated because of the risk for inducing hypoglycemia [Wakeling et al 2017]. * Bone age advancement and puberty. Monitoring for signs of premature adrenarche, fairly early and accelerated central puberty, and insulin resistance is very important in individuals with SRS. Personalized treatment with GnRH analogs for at least two years in children with evidence of central puberty (starting no later than age 12 years in girls and age 13 years in boys) can be considered to preserve adult height potential [Wakeling et al 2017]. Hypoglycemia should be prevented and aggressively managed if present. * Monitoring for urinary ketones after prolonged fasting (including when infants start sleeping through the night) or excess physical activity or with illness * Frequent feeding; avoidance of long fasting between feeds (in infants: ≤4 hours) * Use of complex carbohydrates Gastrointestinal disorders should be treated early and adequately. It is critical that attention to growth and nutrition begin in infancy. Infants with SRS usually have poor muscle mass and often have feeding difficulties in addition to inherent growth disturbance. In one study gastrointestinal issues, feeding disorders, and/or malnutrition were seen in 70% of individuals [Marsaud et al 2015]. Therefore, aggressive feeding measures are often required, but there must be careful monitoring to avoid too rapid a rate of postnatal weight catch up, which has been associated with subsequent increased metabolic risk. Recommended strategies include: * Use of nutritional and caloric supplements; * Treatment of gastroesophageal reflux with appropriate medications, including proton pump inhibitors and H-2 histamine blockers; * Speech or occupational therapy for oral motor problems and feeding aversion; * The use of cyproheptadine, an appetite stimulant which has been shown to have a positive effect on weight and growth velocity [Lemoine et al 2018]; * Use of enteral feeding with gastrostomy or jejunostomy to address extreme cases of feeding aversion and/or gastroesophageal reflux with or without fundoplication limited to extreme cases where other measures have been unsuccessful [Wakeling et al 2017]. With non-volitional feeding, too rapid and excessive weight gain must be avoided. Skeletal abnormalities. The most common orthopedic problem is limb length discrepancy, which often can be several centimeters and involve upper and/or lower extremities. Functionally, this is most significant for lower extremity asymmetry because of the impact on gait. Lower limb length discrepancy exceeding 2 cm can lead to compensatory scoliosis and thus requires intervention. Initial treatment can include the use of a shoe lift. In older children, limb lengthening with distraction osteogenesis has become a more widely applied procedure. When single segment limb lengthening is sufficient, the limb lengthening is generally done prior to completion of growth but close to final height with femoral internal distracters [Goldman et al 2013]. For young children with leg length discrepancy greater than 4 cm, lengthening is done in the lower segment (tibia) with external fixators [Goldman et al 2013]. Scoliosis and kyphosis are a common problem in SRS [Yamaguchi et al 2015]. The relationship of lower limb length asymmetry to scoliosis is not clear, but many children with limb length asymmetry will develop a compensatory scoliosis. Treatment with monitoring and bracing initially is indicated. Many individuals will need corrective surgery [Yamaguchi et al 2015]. Neurodevelopment * For infants with hypotonia, referral to an early-intervention program and physical therapy * For children with evidence of delay, referral for early intervention, speech and language therapy, and occupational and physical therapy as indicated. * For school-age children, working with the school system to address learning disabilities through appropriate neuropsychological testing and an individualized educational plan, including therapeutic interventions as indicated * Referral for psychological counseling as needed to address psychosocial and body image issues Craniofacial anomalies. For those children with severe micrognathia, cleft palate, or complex dental relationships, management by a multidisciplinary cleft palate and craniofacial team is recommended. Early dental care, orthodontia for dental crowding, and maxillofacial surgery may be needed for older children once growth is completed. Otherwise, dental hygiene and dental crowding can be appropriately managed in a routine manner by pediatric dentists and orthodontists. Genitourinary abnormalities. Cryptorchidism and hypospadias is best managed by a pediatric urologist. Males with micropenis and females with internal genitourinary anomalies (some are born with Mayer-Rokitansky-Kuster-Hauser syndrome) benefit from referral to a multidisciplinary disorders of sex development (DSD) center. ### Surveillance Monitoring guidelines of children with SRS has been well outlined in the international consensus statement for diagnosis and management of SRS [Wakeling et al 2017]. The following are appropriate: * Monitoring of growth with special attention to growth velocity and excessive weight gain * Monitoring of urine ketones and blood glucose for ketotic hypoglycemia is of major importance especially in infancy and in older children with a large head circumference, lean body habitus, and poor appetite. Monitoring urine ketones to prevent hypoglycemia should be peformed in infants when frequency of feeding is being reduced, in all children who are acutely ill with decreased feeding or have fevers, and in older children at times of increased physical activity. * At each well-child visit in early childhood, examination and measurement of limb length discrepancy. Infant lengths should be measured for both legs, both lengths recorded, and the longer entered on a growth curve. For measuring height in older children, an appropriate-sized lift sufficient to level the hips should be placed under the foot of the shorter lower extremity. * Examination for presence or scoliosis at each visit * Monitoring for early and aggressive adrenarche and early onset of central puberty because of the risk of rapid bone age advancement and reduced final height despite a long course of GH therapy * Close monitoring for developmental delays, especially motor and speech and language development ### Agents/Circumstances to Avoid Avoid prolonged fasting in infants and young children because of the risk for hypoglycemia. Avoid elective surgery whenever possible. If surgery is unavoidable, physicians must be aware of the risk for hypoglycemia, hypothermia, difficult healing, and difficult intubation (due to abnormal tooth distribution and small mandible, which affect airway visualization and intubation process). ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Silver-Russell Syndrome	c0175693	25,651	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1324/	2021-01-18T20:56:58	{"mesh": ["D056730"], "synonyms": ["Russell-Silver Syndrome"]}
A number sign (#) is used with this entry because trichorhinophalangeal syndrome type II (TRPS2), also known as Langer-Giedion syndrome, is a contiguous gene syndrome on 8q24.1, involving loss of functional copies of the TRPS1 (604386) and EXT1 (608177) genes. TRPS type II combines the clinical features of trichorhinophalangeal syndrome type I (190350) and multiple exostoses type I (133700), which are caused by mutations in the TRPS1 and EXT1 genes, respectively. See also Cornelia de Lange syndrome-4 (CDLS4; 614701), caused by mutation in the RAD21 gene (606462), which lies on 8q24 between TRPS1 and EXT1. Clinical Features Hall et al. (1974) described a condition that they called the Langer-Giedion syndrome in which affected individuals had multiple dysmorphic facial features including large, laterally protruding ears, a bulbous nose, an elongated upper lip, as well as sparse scalp hair, winged scapulae, multiple cartilaginous exostoses, redundant skin, and mental retardation. Kozlowski et al. (1977) reported 2 unrelated patients, a girl and a boy, and suggested that the condition may have been described by Ale and Calo (1961). Murachi et al. (1981) described affected father and daughter, suggesting autosomal dominant inheritance. The father was mildly mentally retarded. They noted previous reports of 9 cases, all sporadic. Langer et al. (1984) described in detail 4 patients who were not mentally retarded, but who did have mental impairment. Delayed speech development and hearing loss were noted as features. They pointed out that most reported cases had been sporadic. They suggested that the term 'tricho-rhino-phalangeal syndrome with exostoses' be used. They also provided a detailed clinical review of 32 previously reported cases. Brenholz et al. (1989) reported LGS in 2 brothers whose mother appeared to have been affected. The maternal grandmother and a maternal first cousin may have been affected. Fryns et al. (1983) and Partington et al. (1991) described hydrometrocolpos and hematometra as complications of this syndrome. Kozlowski et al. (1977) and Partington et al. (1991) described ureteral reflux requiring reimplantation of the ureters in the bladder. In a patient with Langer-Giedion syndrome and interstitial 8q deletion, Ramos et al. (1992) found persistent cloaca and the prune belly sequence (100100). Morioka et al. (1999) described a patient with Langer-Giedion syndrome associated with submucous cleft palate. Stevens and Moore (1999) described a girl with Langer-Giedion syndrome with deletion of 8q and the unusual findings of bilateral tibial hemimelia (275220) and unilateral absence of the ulna. Turleau et al. (1982) had reported an 8-year-old boy with LGS and bilateral tibial hemimelia. Although no genes involving limb development in the human had been identified in the 8q24.1 critical LGS region, 2 mouse syndromes that involve limb abnormalities mapped to the homologous chromosome region, 9A1-A4: 'luxoid' (absent toes, radial and tibial hemimelia, preaxial polydactyly, bent tail, and oligospermia) and 'aft' (abnormal feet and tail). Riedl et al. (2004) described a girl with TRPS II and growth hormone deficiency (see 262400) causing pronounced short stature (-4.8 SD). The patient had an interstitial deletion at 8q24.1 of 12 to 15 Mb. The deletion spanned all genes from CSMD3 (608399) to at least ANXA13 (602573), including the TRPS1 (604386) and EXT1 (608177) genes. Growth hormone deficiency was indicated by diminished response in 3 stimulation tests and a striking response to growth hormone therapy. This was apparently the first observation of combined TRPS II and growth hormone deficiency. Schinzel et al. (2013) reported follow-up of 4 persons with TRPS2 into adulthood and reviewed the limited available literature on adults with TRPS2. Most patients had borderline or mild cognitive impairment, with a few with normal intelligence; patients with TRPS2 performed better in practical skills than their academic achievement would suggest. Some patients developed seizures at variable ages. Scoliosis was most often mild. Exostoses typically did not progress further after puberty, and in some patients, became less prominent. However, serious complications related to cervical spinal exostoses, including stroke and spinal cord compression, were occasionally reported. No cases with malignant transformation of exostoses were identified, although the number of patients followed was too low to define malignancy risk. Almost all males lost their hair at or soon after puberty, and some developed gynecomastia. Growth hormone deficiency was infrequently observed. Serious complications related to the eye, ear, and heart were rare. Cytogenetics Buhler et al. (1980) reported the case of a teenage girl with features suggestive of Langer-Giedion syndrome associated with terminal deletion of 8q: the band q24 was missing from one chromosome 8. Pfeiffer (1980) described deletion of a segment (q13-22) of the long arm of chromosome 8 in a mentally retarded boy with Langer-Giedion syndrome. Additional features included colobomata of the iris and defect of the fourth and fifth fingers. Wilson et al. (1981) found interstitial deletion of 8q22.8-q24.1 in a 17-year-old patient with multiple exostoses and developmental delay. Exostoses were first apparent at age 4 years. The patient lacked the typical nose and coned epiphyses of the Langer-Giedion syndrome. Gorlin et al. (1982) found normal chromosomes on prophase banding in 2 patients. Turleau et al. (1982) concluded that 8q23 is the 'critical segment,' not 8q22. Zaletajev and Marincheva (1983) attributed LGS in their patient to interstitial deletion of 8q22. Bowen et al. (1985) described an 18-year-old intellectually normal male with LGS and a small deletion of bands 8q24.11-q24.12. In addition, he had an apparently balanced de novo translocation (2;9)(q21;q13). Neither abnormality was found in the parents. The risk of LGS in any child of the proband would presumably be 50%. Okuno et al. (1987) described a typical case with interstitial deletion of 8q24.13-q24.22. Zaletaev et al. (1987) found deletion in 8q in 3 unrelated patients with LGS. The 'critical' region was identified as 8q24.11-q24.13. The findings of Fennell et al. (1989) likewise supported the view that the critical segment for LGS is proximal to or involves a proximal part of 8q24.1. Mapping In reviewing 12 cases from the literature, Buhler and Malik (1984) suggested that the shortest region of overlap of the 8q deletion is in band 8q24.1. They raised the question of whether type I trichorhinophalangeal syndrome may be caused by mutation at the same locus or region. Supporting this suggestion was the description of TRPS I with probable deletion in the same region of 8q (Hamers et al., 1983) and appreciation that the presence or absence of exostoses may be the other 'symptom' that distinguishes types I and II. The fact that the multiple exostoses of LGS are indistinguishable in radiographic features and natural history from those of the long-recognized autosomal dominant disorder 'multiple hereditary exostoses' (see EXT, 133700) suggested that a locus for EXT was situated on 8q. Brocas et al. (1986) showed that the thyroglobulin locus, located at 8q24, is intact in LGS. This confirmed the distal location previously defined for LGS and assigned the critical region for the disorder to the proximal part of band 8q24 (8q24.11-q24.13). Buhler et al. (1987) concluded that the Langer-Giedion syndrome is due to a deletion extending from 8q24.11 to 8q24.13, whereas TRPS I is caused by an even smaller deleted segment, namely, 8q24.12. They described a case of TRPS I with a mosaic deletion of that band. Ludecke et al. (1989) found 2 RFLPs in an anonymous DNA probe that defined the D8S48 locus within the Langer-Giedion syndrome chromosome region. Both polymorphisms were informative in the family of a Langer-Giedion patient carrying a de novo interstitial deletion 8q23-q24.1. Lack of transmission of a maternal haplotype indicated that the deletion occurred during maternal gametogenesis. Ludecke et al. (1989) described the microdissection of the Langer-Giedion syndrome region on chromosome 8 from GTG-banded metaphase chromosomes (G-banding with trypsin-Giemsa) and the universal enzymatic amplification of the dissected DNA. Eighty percent of clones from this library (total yield 20,000) identified single-copy DNA sequences. Half of the clones detected deletions in 2 patients with LGS. Ten of the clones were assigned to the deleted region in Langer-Giedion syndrome (8q23.2-q24.11) based on Southern blot analysis of DNA from 2 patients. The results of Ludecke et al. (1989) demonstrated that thousands of region-specific probes can be isolated in a short period of time. Microdissection and microcloning have been applied successfully to various chromosome regions in Drosophila and mouse, but conventional microtechniques are too coarse and inefficient, especially on unbanded chromosomes, for analysis of the human genome. Ludecke et al. (1991) used 13 anonymous DNA markers from an 8q24.1-specific microdissection library, as well as MYC (190080) and TG (188450) gene probes, to map the deletion breakpoints in 16 patients with LGS. Twelve patients had a cytogenetically visible deletion, 2 had an apparently balanced translocation, and 2 had an apparently normal karyotype. In all cases except 1 translocation patient, loss of genetic material was detected. The DNA markers fell into 10 deletion intervals. Clone L48 (D8S51) defined the shortest region of deletion overlap, which was estimated to be less than 2 Mb. The clones that flanked the shortest region of deletion overlap recognized evolutionarily conserved sequences. Parrish et al. (1991) isolated 8 DNA clones that were found to lie within the deletion of at least 1 of 3 patients with LGS. One clone identified sequences that were missing from 1 copy of chromosome 8 in all 3 patients. Molecular Genetics Using YAC cloning, Southern blotting, PCR analysis, and fluorescence in situ hybridization in the study of chromosome 8 deletions, translocations, an inversion, and an insertion in patients with TRPS I, Langer-Giedion syndrome, or multiple exostoses type I, Ludecke et al. (1995) obtained information indicating that the TRPS1 gene (604386) maps more than 1,000 kb proximal to the EXT1 gene and that both genes are affected in Langer-Giedion syndrome. They concluded that the Langer-Giedion syndrome is not due to pleiotropic effects of mutations in a single gene, but that it is a true contiguous gene syndrome. Hou et al. (1995) constructed a physical map covering 4 Mb of 8q24.1 and used this map to refine the location of the genes responsible for LGS. The map was composed of overlapping YAC clones that were identified and ordered in relation to sequence tagged sites mapped to the Langer-Giedion chromosomal region on somatic cell hybrids. The minimal region of overlap of LGS deletions, previously identified by analysis of 15 patients, was placed on the map by analysis of 2 patients whose deletions defined the end points. The chromosome 8 breakpoint of a balanced t(8;9)(q24.1;q33.3) translocation from a patient with TRPS I was found to be located just within the proximal end of the minimal deletion region. A deletion of 8q24.11-q24.3 in a patient with multiple exostoses was found to overlap the distal end of the LGS deletion region, indicating that the EXT1 gene is distal to the TRPS1 gene and providing further support for the hypothesis that LGS is due to loss of functional copies of both the TRPS1 and the EXT1 genes. INHERITANCE \- Autosomal dominant GROWTH Height \- Postnatal onset of mild growth retardation HEAD & NECK Head \- Microcephaly Ears \- Hearing loss \- Large protruding ears Eyes \- Deep-set eyes \- Exotropia Nose \- Bulbous nose \- Broad nasal bridge \- Tented, thickened alae nasi \- Prominent philtrum RESPIRATORY Airways \- Recurrent upper respiratory tract infections CHEST Ribs Sternum Clavicles & Scapulae \- Rib exostoses \- Scapulae exostoses \- Winged scapulae GENITOURINARY Ureters \- Hydrometrocolpos \- Ureteral reflux SKELETAL Spine \- Scoliosis Limbs \- Multiple exostoses of long tubular bones \- Perthes-like femoral head changes \- Predisposition to fracture \- Hyperextensible joints Hands \- Cone-shaped epiphyses of phalanges \- Syndactyly SKIN, NAILS, & HAIR Skin \- Redundant skin in infancy \- Nevi Nails \- Brittle nails Hair \- Sparse scalp hair NEUROLOGIC Central Nervous System \- Mental retardation \- Delayed speech development \- Hypotonia LABORATORY ABNORMALITIES \- Chromosome deletion extending from 8q24.11 to 8q24.13 MISCELLANEOUS \- Majority of cases sporadic \- Male predominance MOLECULAR BASIS \- A contiguous gene syndrome caused by mutations in the zinc finger transcription factor TRPS1 (TRPS1, 604386 ) and the exostosin 1 gene (EXT1, 133700 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	TRICHORHINOPHALANGEAL SYNDROME, TYPE II	c0023003	25,652	omim	https://www.omim.org/entry/150230	2019-09-22T16:39:06	{"doid": ["4998"], "mesh": ["D015826"], "omim": ["150230"], "orphanet": ["502"], "synonyms": ["Alternative titles", "LANGER-GIEDION SYNDROME", "CHROMOSOME 8q24.1 DELETION SYNDROME"], "genereviews": ["NBK425926"]}
## Description Restless legs syndrome (RLS) is a neurologic sleep/wake disorder characterized by uncomfortable and unpleasant sensations in the legs that appear at rest, usually at night, inducing an irresistible desire to move the legs. The disorder results in nocturnal insomnia and chronic sleep deprivation (Bonati et al., 2003). For additional information and a discussion of genetic heterogeneity of restless legs syndrome, see RLS1 (102300). Mapping Chen et al. (2004) characterized 15 large and extended multiplex pedigrees consisting of 453 subjects, of whom 134 were affected with restless legs syndrome. A weighted average correlation of 0.17 between first-degree relatives was obtained, and heritability was estimated to be 0.60 for all types of relative pairs, indicating that the disorder was highly heritable in this cohort. Model-free linkage analysis identified 1 novel significant RLS susceptibility locus on 9p24-p22 with a multipoint nonparametric linkage (NPL) score of 3.22. Suggestive evidence of linkage indicated by NPL scores between 2 and 3 were found on chromosomes 3, 4, 5, and 6. Model-based linkage analysis, with the assumption of an autosomal dominant mode of inheritance, validated the linkage of RLS to 9p24-p22 in 2 families (2-point lod score of 3.77; multipoint lod score of 3.91). A marker between D12S1044 and D12S78 on chromosome 12q22-q23, and 2.4 cM from D12S78, yielded an NPL score of 1.29, which Chen et al. (2004) suggested might provide indirect confirmation of an RLS locus (RLS1; 102300) on chromosome 12q22-q23. Ray and Weeks (2005) concluded, contrary to the findings of Chen et al. (2004), that there is no convincing evidence of linkage for RLS on 9p. In a rebuttal, Chen et al. (2005) defended their analysis as methodologically sound and pointed out that by personal communication they had information on the finding of a 9p24-p22 RLS locus in a large family in Germany studied by another research group. Liebetanz et al. (2006) reported a large Bavarian family in which 16 individuals had RLS, including 9 with onset before age 32 years and 7 with onset after age 32 years. Transmission disequilibrium tests indicated linkage to D9S1810. Genomewide linkage analysis followed by fine mapping yielded maximum 2-point and multipoint lod scores of 3.88 and 3.78, respectively, at D9S285. The 1-unit lod interval delineated an 11.1-cM region between D9S256 and D9S157. These results were obtained when considering only early-onset patients and unaffected family members. When all affected individuals, regardless of age at onset, were included in the linkage analysis, lod scores were solidly negative for the entire region on chromosome 9p; the authors postulated intrafamilial heterogeneity. Schormair et al. (2008) identified association of RLS with PTPRD (601598) at 9p24-p23 in 2,458 affected individuals and 4,749 controls from Germany, Austria, Czech Republic, and Canada. Two independent SNPs in the 5-prime UTR of splice variants expressed predominantly in the central nervous system showed highly significant P values (rs4626664, P(nominal/lambda-corrected) = 5.91 x 10(-10), odds ratio = 1.44; and rs1975197, P(nominal/lambda-corrected) = 5.81 x 10(-9), odds ratio = 1.31). These 2 association signals are 0.41 Mb apart and map to introns 8 and 10 of PTPRD, within 2 separate linkage disequilibrium blocks. Sequence analysis revealed no mutations in 35 coding and 10 noncoding exons of PTPRD among 9 affected individuals from an RLS3-linked family, 3 index cases from families with RLS in which linkage to RLS3 was not excluded, and 1 control compared to the reference sequence. The familial relative risk figures estimated by the risk to sibs of an affected individual (lambda-S) were all below 1.04 and explain only a minor portion of the original RLS3 linkage signal. The RLS-associated SNPs are common and showed weak effects (rs4626664, odds ratio = 1.44, 95% confidence interval = 1.3 to 1.6; rs1975197, odds ratio = 1.31, 95% confidence interval = 1.2 to 1.4). Schormair et al. (2008) failed to detect rare alleles with strong effects within this gene that could explain the linkage signal. The association of 2 independent signals strengthened the evidence for PTPRD as a gene influencing risk of RLS. Lohmann-Hedrich et al. (2008) reported a German family with RLS spanning 4 generations in an autosomal dominant pattern of inheritance. Disease onset was mainly in childhood or adolescence. Linkage analysis identified a locus on chromosome 9p (maximum lod score of 3.60 at all markers between D9S976 and D9S2183) that was separated from RLS3 by approximately 5 cM (2.3 Mb). Lohmann-Hedrich et al. (2008) termed this locus RLS3* to distinguish it from RLS3. Twelve patients shared a haplotype flanked by D9S974 and D9S1118 in a 9.9-Mb region that was centromeric to RLS3. However, 11 patients shared a larger haplotype extending telomeric to D9S2189 that overlapped with the RLS3 locus. Several affected individuals had a cooccurrence of psychiatric disorders. Molecular Genetics Chen et al. (2004) found no mutations in 3 genes from the 9p24-p22 region that were considered to be strong RLS candidates on the basis of their location and physiology: MPDZ (603785), SLC1A1 (133550), and KCNV2 (607604). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	RESTLESS LEGS SYNDROME, SUSCEPTIBILITY TO, 3	c1864875	25,653	omim	https://www.omim.org/entry/610438	2019-09-22T16:04:30	{"omim": ["610438"]}
Beta-thalassemia (BT) major is a severe early-onset form of BT (see this term) characterized by severe anemia requiring regular red blood cell transfusions. ## Epidemiology The annual incidence of symptomatic cases is estimated at 1/100,000 worldwide and 1/10,000 in the EU. The prevalence of this form is not known. ## Clinical description Onset is during infancy with severe anemia, failure to thrive and progressive pallor. Feeding problems, diarrhea, irritability, recurrent bouts of fever, and progressive enlargement of the abdomen caused by splenomegaly and hepatomegaly may occur. Untreated or poorly transfused patients show growth retardation, pallor, jaundice, poor musculature, genu valgum, leg ulcers, formation of masses due to extramedullary hematopoiesis, and skeletal changes including deformities in the long bones of the legs and typical craniofacial changes such as bossing of the skull, prominent malar eminence, depression of the bridge of the nose, tendency to a mongoloid slant of the eye, and maxillae hypertrophy, which tends to expose upper teeth. In regularly transfused patients, growth and development tend to be normal but complications related to iron overload may develop, including growth retardation and failure or delay of sexual maturation. Later-onset iron overload complications include dilated myocardiopathy, arrhythmias, liver fibrosis and cirrhosis, diabetes mellitus, and insufficiency of the parathyroid, thyroid, pituitary, and, less commonly, adrenal glands. Other complications are hypersplenism, venous thrombosis and osteoporosis. ## Etiology BT is caused by point mutations or, more rarely, deletions in the HBB gene (11p15.5), leading to reduced (beta+) or absent (beta0) synthesis of the beta-chains of hemoglobin (Hb). Mutations causing BT major are homozygous or compound heterozygous. ## Diagnostic methods Diagnosis is suspected in infants younger than 2 years of age with severe microcytic anemia, mild jaundice and hepatosplenomegaly. Blood analysis shows reduced Hb levels (< 7 g/dl), mean corpuscular volume (MCV) > 50 < 70 fl, and mean corpuscular Hb (MCH) > 12 < 20 pg, anisopoikilocytosis and presence of erythroblasts in the peripheral blood smear. Hb analysis and molecular genetic analysis provide diagnostic confirmation. ## Differential diagnosis Differential diagnosis is usually simple but may include genetic sideroblastic anemias, congenital dyserythropoietic anemias, and other conditions with high levels of HbF (such as juvenile myelomonocytic leukemia and aplastic anemias; see these terms). ## Antenatal diagnosis Prenatal diagnosis is possible by amniocentesis. Both disease-causing alleles must be identified before prenatal testing can be performed. ## Genetic counseling Transmission is autosomal recessive. Genetic counseling provides information for patients and at-risk couples (i.e. both carriers) regarding the mode of inheritance and transmission. Preimplantation genetic diagnosis may be available for families in which the disease-causing mutations have been identified. ## Management and treatment Treatment is based on lifelong transfusions to correct anemia, suppress erythropoiesis, and inhibition of gastrointestinal iron absorption, which occurs in non-transfused patients due to increased, although ineffective, erythropoiesis. Iron chelation should be started once patients have had 10-15 transfusions or when ferritin levels are above 1000 ng/ml. Management should also include treatment of iron overload-related complications (growth deficiency, delayed puberty, hypogonadism, hypopara- and hypothyroidism, diabetes, and osteoporosis). Splenectomy may be required. Bone marrow transplantation (BMT) is at present the only available definitive cure. Recently a first patient was successfully treated with gene therapy. ## Prognosis Patients who do not receive regular transfusions and iron chelation usually die before the 2nd or 3rd decade whereas survival is higher in regularly transfused and chelated patients. Cardiac complications are still the major cause of death. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Beta-thalassemia major	c0002875	25,654	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=231214	2021-01-23T18:57:05	{"mesh": ["D017086"], "omim": ["613985"], "umls": ["C0002875"], "icd-10": ["D56.1"], "synonyms": ["Cooley anemia", "Mediterranean anemia"]}
Episodic ataxia type 2 (EA2) is the most frequent form of Hereditary episodic ataxia (EA; see this term) characterized by paroxysmal episodes of ataxia lasting hours, with interictal nystagmus and mildly progressive ataxia. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Familial paroxysmal ataxia	c1720416	25,655	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=97	2021-01-23T18:45:23	{"gard": ["9602"], "mesh": ["C535506"], "omim": ["108500"], "umls": ["C1720416"], "icd-10": ["G11.8"], "synonyms": ["Episodic ataxia type 2"]}
A form of hypotonia-cystinuria type 1 syndrome characterized by mild to moderate intellectual disability in addition to classic hypotonia-cystinuria syndrome phenotype (cystinuria type 1, generalised hypotonia, poor feeding, growth retardation, and minor facial dysmorphism). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Atypical hypotonia-cystinuria syndrome	c1848030	25,656	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=238523	2021-01-23T17:10:49	{"mesh": ["C564710"], "omim": ["606407"], "icd-10": ["E72.0"], "synonyms": ["Atypical HCS"]}
A number sign (#) is used with this entry because of evidence that Senior-Loken syndrome-8 (SLSN8) is caused by homozygous or compound heterozygous mutation in the WDR19 gene (608151) on chromosome 4p14. For a general phenotypic description and discussion of genetic heterogeneity of Senior-Loken syndrome, see SLSN1 (266900). Clinical Features Coussa et al. (2013) studied a consanguineous French Canadian family with an atypical form of retinitis pigmentosa (RP) as well as renal cysts. The 50-year-old male proband had bilateral visual acuities of hand motion only, with severe constriction of visual fields (5 degrees); electroretinographic responses were undetectable. Fundus examination showed fine bone spicules in the periphery and severely attenuated vessels in both eyes, with slight temporal pallor of the optic discs. The patient also exhibited significant macular atrophy that had a 'bear claw' appearance on fundus autofluorescence. Optical coherence tomography (OCT) revealed considerable thinning of the fovea and a poorly delineated photoreceptor layer with extensive loss of the inner/outer segment junctions, as well as foveal debris. Because the patient had a family history of 'kidney problems,' a pelvic ultrasound was performed, which showed bilateral large exophytic renal cysts, although urinalysis and blood biochemistry were within normal ranges. The patient also had mild cognitive impairment. Other family members with RP included the proband's deceased mother, 4 sisters, and a maternal aunt, several of whom also had subclinical renal cysts. Molecular Genetics In 3 unrelated patients with nephronophthisis and retinal dystrophy, Halbritter et al. (2013) identified biallelic mutations in the WDR19 gene (608151.0006-608151.0007 and 608151.0010-608151.0011). The patients were ascertained from a larger cohort of 1,056 patients with nephronophthisis-related disorders who underwent genetic analysis; 2 of the 3 Senior-Loken patients exhibited additional features of a ciliopathy, with dilation of the intrahepatic bile ducts in 1 and pancreatic and hepatic cysts in the other. In affected members of a consanguineous French Canadian family with retinitis pigmentosa and renal cysts, who were negative for mutation in all known autosomal recessive RP-associated genes, Coussa et al. (2013) performed whole-exome capture and next-generation sequencing and identified homozygosity for a missense mutation in the WDR19 gene (L710S; 608151.0001). Screening of 96 patients with a diagnosis of Senior-Loken syndrome revealed WDR19 mutations in 5 probands (see, e.g., 608151.0006-608151.0007 and 608151.0012-608151.0013). INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Decreased visual acuity \- Markedly constricted visual field \- Bone-spicule appearance in periphery \- Severely attenuated vessels \- Slight temporal pallor of optic discs \- Significant macular atrophy with 'bear claw' pattern on fundus autofluorescence \- Undetectable responses on electroretinography \- Thinning of fovea on optical coherence tomography (OCT) \- Poorly delineated photoreceptor layer on OCT \- Loss of inner/outer segment junctions on OCT \- Foveal debris on OCT ABDOMEN Liver \- Dilatation of intrahepatic bile ducts \- Hepatic cysts Pancreas \- Pancreatic cysts GENITOURINARY Kidneys \- Nephronophthisis \- Large exophytic cysts NEUROLOGIC Central Nervous System \- Mild cognitive impairment LABORATORY ABNORMALITIES \- Normal urinalysis \- Normal blood biochemistry MOLECULAR BASIS \- Caused by mutation in the WD repeat-containing protein-19 (WDR19, 608151.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	SENIOR-LOKEN SYNDROME 8	c0403553	25,657	omim	https://www.omim.org/entry/616307	2019-09-22T15:49:24	{"mesh": ["C537580"], "omim": ["616307"], "orphanet": ["3156"]}
Eosinophilic fasciitis is a very rare condition in which muscle tissue underneath the skin, called fascia, becomes swollen and thick. Rapid swelling can occur in the hands, arms, legs, and feet. People with this condition have a buildup of eosinophils, a type of white blood cell, in the affected fascia and muscles. The exact cause of this condition is unknown. Corticosteroids and other immune-suppressing medications are used to relieve the symptoms. Eosinophilic fasciitis is similar in appearance to scleroderma. However, in contrast with systemic sclerosis, internal organ involvement in eosinophilic fasciitis is generally absent. Some researchers believe that eosinophilic fasciitis may be a variant of morphea (localized scleroderma). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Eosinophilic fasciitis	c0264005	25,658	gard	https://rarediseases.info.nih.gov/diseases/6351/eosinophilic-fasciitis	2021-01-18T18:00:42	{"mesh": ["C562487"], "omim": ["226350"], "orphanet": ["3165"], "synonyms": ["Shulman syndrome", "EF"]}
A number sign (#) is used with this entry because of evidence that Cole-Carpenter syndrome-2 (CLCRP2) is caused by compound heterozygous mutation in the SEC24D gene (607186) on chromosome 4q26. For a general phenotypic description and discussion of genetic heterogeneity of Cole-Carpenter syndrome, see CLCRP1 (112240). Clinical Features Garbes et al. (2015) reported a German boy with multiple pre- and postnatal fractures and craniofacial malformations. At birth, he was noted to have turricephaly, exophthalmos, downslanting palpebral fissures, angular root of nose, retrognathia, and gaping fontanels. Ultrasound and x-ray examination showed both new and old fractures involving the right clavicle, multiple ribs, and both radii, as well as extensive ossification defects of the cranium and craniosynostosis. Additional features observed at 9 months of age included hypertelorism, midface hypoplasia, high palate, and slight dysplasia of right concha. At 4.3 years of age, he had delayed motor development due to recurrent fractures of the extremities, but he was able to walk, run, and climb stairs. CT scan showed dilated ventricles and subarachnoid spaces, in addition to a large frontoparietoapical ossification defect, for which he wore a helmet during physical activities. At 7 years of age he had moderately reduced bone mineral density, macrocephaly of postnatal onset, and short stature, with facial features reminiscent of Cole-Carpenter syndrome. Garbes et al. (2015) also studied 2 female fetuses from terminated pregnancies in a second German family. Prenatal ultrasound had shown multiple fractures of the long bones, mildly bent extremities, and a thin, poorly ossified skull. X-ray examination of 1 of the fetuses revealed a calvarium with severely reduced and largely absent ossification, in contrast to normal ossification of the skull base and only mildly disturbed ossification and shape of the remainder of the skeleton. The ribs were thin and fractures were noted, but the thorax was not severely hypoplastic, suggesting that the skeletal defects were nonlethal. Moosa et al. (2016) reported a 16-month-old girl, born to nonconsanguineous Chinese parents, with a more classic OI phenotype and a mutation in the SEC24D gene. Short long bones were noted on prenatal ultrasound at 18 weeks' gestation. She presented during the neonatal period with blue-gray sclerae, osteopenia, wormian bones, and deformities of the the long bones. No dysmorphic craniofacial features were present. Her coronal sutures were patent and her anterior fontanel was enlarged but not to the extent described in the patients reported by Garbes et al. (2015). She sustained a fracture of the right proximal femur at age 12 months followed by a fracture of the right tibia at age 15 months; both were treated successfully. Zhang et al. (2017) reported 2 unrelated patients, both born of nonconsanguineous Chinese parents, with mutations in the SEC24D gene and a clinical diagnosis of OI. The first proband was a 23-year-old man (family 1) who had recurrent fractures beginning at age 1 month, deformities in both lower limbs with severe bowing of the left femur, and facial dysmorphism, including downslanting palpebral fissures, frontal protrusion, left ear dysplasia, and micrognathia. His anterior fontanel was not closed and CT of the cranium showed skull deformities associated with a broad frontoapical ossification defect, a widened sagittal suture, and wormian bones. He had dentinogenesis imperfecta but did not exhibit blue sclerae or hearing loss. The second proband was a 7-year-old boy (family 2) who had recurrent fractures beginning at age 1.5 years and severe bowing in the left femur. He had dentinogenesis but did not have blue sclerae or hearing loss. His anterior fontanel was not closed and he had no obvious facial dysmorphism. Zhang et al. (2017) noted some similarities between the proband from family 1 and the patient reported by Garbes et al. (2015) and suggested that facial dysmorphisms may be characteristic of OI patients with SEC24D mutations. Takeyari et al. (2018) reported a 15-year-old Japanese boy with features consistent with Cole-Carpenter syndrome-2. The boy had growth failure with a short trunk and craniofacial abnormalities including ocular proptosis, marked frontal bossing, midface hypoplasia, and micrognathia. He had a wide open fontanel as well as low bone mineral density (BMD), with a healed iliac bone fracture observed at age 10 years. Skeletal imaging showed wormian bones, lordosis, and long thin bones. Brain imaging revealed hydrocephalus and basilar impression. Because of his low BMD and basilar impression, he received periodic bisphosphonate therapy from 6 years of age. His BMD improved, but basilar impression did not change. Molecular Genetics In a 7-year-old German boy with CLCRP2, Garbes et al. (2015) performed exome sequencing and identified compound heterozygosity for a missense mutation (S1015F; 607186.0001) and a nonsense mutation (Q205X; 607186.0002) in the SEC24D gene. His unaffected parents were each heterozygous for 1 of the mutations. In another German family in which 2 pregnancies with female fetuses had been terminated due to what appeared to be a severe form of osteogenesis imperfecta (OI; see 166200), Garbes et al. (2015) identified the S1015F mutation and another missense mutation (Q978P; 607186.0003) in SEC24D. Both affected fetuses were compound heterozygous for the mutations, and the unaffected parents and an unaffected sister were each heterozygous for 1 of the mutations. The mother of the first family and the father of the second family, who were both descended from families residing in southwestern Germany, carried the S1015F mutation; haplotype analysis revealed a 14-Mb shared region between rs6533681 and rs2255457 (chr4:114,309,589-128,554,154), confirming that S1015F represents a founder mutation. Garbes et al. (2015) noted overlap between features of these patients and individuals with craniolenticulosutural dysplasia (CLSD; 607812), which is caused by mutation in a related gene (SEC23A; 610511), but concluded that the phenotype of their patients more closely resembled that of Cole-Carpenter syndrome. In a 16-month-old girl, born of nonconsanguineous Chinese parents, with a clinical diagnosis of moderate OI, Moosa et al. (2016) identified compound heterozygous mutations in the SEC24D gene (607186.0004-607186.0005). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the phenotype in the family. In 2 unrelated males, both born of nonconsanguineous Chinese parents, with a clinical diagnosis of OI, Zhang et al. (2017) identified compound heterozygous mutations in the SEC24D gene (607186.0006-607186.0009). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the phenotype in the family. In a 15-year-old Japanese boy with Cole-Carpenter syndrome-2, Takeyari et al. (2018) identified compound heterozygous mutations in the SEC24D gene (R313H, 607186.0008 and R484X, 607186.0010). The R313H mutation was inherited from his mother, but DNA from his father was unavailable for testing. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, were not present in public or in-house exome databases. INHERITANCE \- Autosomal recessive GROWTH Height \- Postnatal growth failure \- Short stature HEAD & NECK Head \- Turricephaly at birth \- Macrocephaly \- Enlarged fontanels \- Anterior fontanel not closed Face \- Frontal bossing \- Triangular face \- Midface hypoplasia \- Microretrognathia Ears \- Dysplasia of concha, unilateral, mild Eyes \- Proptosis \- Hypertelorism \- Blue sclerae \- Downslanting palpebral fissures Nose \- Angular root of nose Mouth \- High palate Teeth \- Dentinogenesis imperfecta CHEST External Features \- Pectus excavatum Ribs Sternum Clavicles & Scapulae \- Thin ribs \- Prenatal rib fractures SKELETAL \- Osteopenia Skull \- Turricephaly at birth \- Macrocephaly \- Skull erosions \- Skull ossification defect \- Coronal craniosynostosis \- Lambdoid craniosynostosis \- Temporal craniosynostosis \- Multiple wormian bones \- Widened sutures \- Wormian bones Spine \- Flattened vertebrae \- Anterior notching of vertebrae \- Posterior wedging of vertebrae \- Mild thoracic kyphosis Pelvis \- Hypoplastic acetabular roof \- High and narrow iliac wings Limbs \- Multiple fractures and deformities of upper and lower extremities \- Metaphyseal abnormalities NEUROLOGIC Central Nervous System \- Hydrocephalus \- Normal intellectual development VOICE \- High-pitched voice PRENATAL MANIFESTATIONS Amniotic Fluid \- Oligohydramnios MISCELLANEOUS \- Evidence of prenatal fractures \- Variable features present MOLECULAR BASIS \- Caused by mutation in the SEC24-related gene family, member D gene (SEC24D, 607186.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	COLE-CARPENTER SYNDROME 2	c1862178	25,659	omim	https://www.omim.org/entry/616294	2019-09-22T15:49:23	{"doid": ["0060438"], "mesh": ["C535963"], "omim": ["616294"], "orphanet": ["2050"]}
Kabuki syndrome is a disorder that affects many parts of the body. It is characterized by distinctive facial features including arched eyebrows; long eyelashes; long openings of the eyelids (long palpebral fissures) with the lower lids turned out (everted) at the outside edges; a flat, broadened tip of the nose; and large protruding earlobes. The name of this disorder comes from the resemblance of its characteristic facial appearance to stage makeup used in traditional Japanese Kabuki theater. People with Kabuki syndrome have mild to severe developmental delay and intellectual disability. Affected individuals may also have seizures, an unusually small head size (microcephaly), or weak muscle tone (hypotonia). Some have eye problems such as rapid, involuntary eye movements (nystagmus) or eyes that do not look in the same direction (strabismus). Other characteristic features of Kabuki syndrome include short stature and skeletal abnormalities such as abnormal side-to-side curvature of the spine (scoliosis), short fifth (pinky) fingers, or problems with the hip and knee joints. The roof of the mouth may have an abnormal opening (cleft palate) or be high and arched, and dental problems are common in affected individuals. People with Kabuki syndrome may also have fingerprints with unusual features and fleshy pads at the tips of the fingers. These prominent finger pads are called fetal finger pads because they normally occur in human fetuses; in most people they disappear before birth. A wide variety of other health problems occur in some people with Kabuki syndrome. Among the most commonly reported are heart abnormalities, frequent ear infections (otitis media), hearing loss, and early puberty. ## Frequency Kabuki syndrome occurs in approximately 1 in 32,000 newborns. ## Causes Kabuki syndrome is caused by mutations in the KMT2D gene (also known as MLL2) or the KDM6A gene. Between 55 and 80 percent of cases of Kabuki syndrome are caused by mutations in the KMT2D gene. This gene provides instructions for making an enzyme called lysine-specific methyltransferase 2D that is found in many organs and tissues of the body. Lysine-specific methyltransferase 2D functions as a histone methyltransferase. Histone methyltransferases are enzymes that modify proteins called histones. Histones are structural proteins that attach (bind) to DNA and give chromosomes their shape. By adding a molecule called a methyl group to histones (a process called methylation), histone methyltransferases control (regulate) the activity of certain genes. Lysine-specific methyltransferase 2D appears to activate certain genes that are important for development. Between 2 and 6 percent of cases of Kabuki syndrome are caused by mutations in the KDM6A gene. This gene provides instructions for making an enzyme called lysine-specific demethylase 6A. This enzyme is a histone demethylase, which means that it helps to remove methyl groups from certain histones. Like lysine-specific methyltransferase 2D, lysine-specific demethylase 6A regulates the activity of certain genes, and research suggests that the two enzymes work together to control certain developmental processes. The KMT2D and KDM6A gene mutations associated with Kabuki syndrome lead to the absence of the corresponding functional enzyme. A lack of the enzymes produced from these genes disrupts normal histone methylation and impairs proper activation of certain genes in many of the body's organs and tissues, resulting in the abnormalities of development and function characteristic of Kabuki syndrome. Some people with Kabuki syndrome have no identified KMT2D or KDM6A gene mutation. The cause of the disorder in these individuals is unknown. ### Learn more about the genes associated with Kabuki syndrome * KDM6A * KMT2D ## Inheritance Pattern When Kabuki syndrome is caused by mutations in the KMT2D gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. When Kabuki syndrome is caused by mutations in the KDM6A gene, it is inherited in an X-linked dominant pattern. The KDM6A gene is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. Most cases of Kabuki syndrome result from a new mutation in one of these genes and occur in people with no history of the disorder in their family. In a few cases, an affected person is believed to have inherited the mutation from one affected parent. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Kabuki syndrome	c0796004	25,660	medlineplus	https://medlineplus.gov/genetics/condition/kabuki-syndrome/	2021-01-27T08:25:19	{"gard": ["6810"], "mesh": ["C537705"], "omim": ["147920", "300867"], "synonyms": []}
## Clinical Features Walsh (1971) described a pigment anomaly in New Guinea natives. The skin is reddish-brown rather than black as in other natives. Melanin is present, however, and increases with age. The color of the hair varies from the usual black to almost white. Nystagmus and photophobia are variable features. An enzymatic defect in melanin formation was posited. Inheritance Walsh (1971) reported many pedigrees with a red pigment anomaly in New Guinea that supported autosomal recessive inheritance. Hair \- Variable from black to almost white Eyes \- Nystagmus \- Photophobia Inheritance \- Autosomal recessive Skin \- Reddish-brown skin color ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	RED SKIN PIGMENT ANOMALY OF NEW GUINEA	c1849451	25,661	omim	https://www.omim.org/entry/266350	2019-09-22T16:22:49	{"mesh": ["C535515"], "omim": ["266350"]}
A number sign (#) is used with this entry because mucopolysaccharidosis type IIIC (MPS3C), also known as Sanfilippo syndrome C, is caused by homozygous or compound heterozygous mutation in the HGSNAT gene (610453), encoding heparan acetyl-CoA:alpha-glucosaminide N-acetyltransferase, on chromosome 8p11. Description Sanfilippo syndrome comprises several forms of lysosomal storage diseases due to impaired degradation of heparan sulfate. The deficient enzyme in Sanfilippo syndrome C, or MPS IIIC, is an acetyltransferase that catalyzes the conversion of alpha-glucosaminide residues to N-acetylglucosaminide in the presence of acetyl-CoA. For a general phenotypic description and a discussion of genetic heterogeneity of Sanfilippo syndrome, see MPS IIIA (252900). Clinical Features Kresse et al. (1976) reported 2 related patients of Greek origin with the phenotype of Sanfilippo syndrome who had normal values of heparan sulfamidase (605270) and alpha-N-acetylglucosaminidase (NAGLU; 609701). Metabolic correction was achieved upon cocultivation with Sanfilippo A and Sanfilippo B (252920) fibroblasts. The authors termed the disorder 'Sanfilippo disease type C.' Klein et al. (1978) identified complete deficiency of acetyl-CoA:alpha-glucosaminide N-acetyltransferase in 3 patients with MPS IIIC. In a note added in proof, they indicated that since submission of the manuscript, they had proved the IIIC defect in 11 cases of the Sanfilippo syndrome. Sewell et al. (1988) reported 2 affected sisters born from a large consanguineous Turkish family with MPS IIIC. The older child presented at 3 months of age with dysmorphic signs, including coarse facies, hypertelorism, low-set ears, depressed nasal bridge, and coarse hair. She had mild hepatosplenomegaly and high lumbar vertebral bodies radiographically. She demonstrated delayed motor development. The younger sister presented at age 16 months with a similar clinical phenotype. Skeletal radiographs showed iliac flaring, practically flat acetabula, and thickened femoral necks. The lumbar vertebral bodies showed ovoid deformities. Urinary heparan sulfate was increased. Ruijter et al. (2008) reported 29 patients from the Netherlands with MPS IIIC. Some of the patients were of Turkish or Moroccan descent. Psychomotor development was reported to be normal in all patients during the first year of life. Onset of behavioral problems or psychomotor retardation became apparent between 1 and 6 years of age. Behavioral problems were severe and included restlessness, chaotic behavior, and temper tantrums. Sleep disturbances were common. Other features included diarrhea, inguinal or umbilical hernia, recurrent upper respiratory tract infection, and seizure. Retinitis pigmentosa was present in 3 patients over age 30. Neurologically, patients showed loss of speech development and developmental decline about 10 years before loss of motor function. The mean age at death was 34 years. Canals et al. (2011) reported 11 unrelated probands with MPS IIIC, including 7 of Spanish origin, 1 from Argentina, and 3 from Morocco. Four of the families were consanguineous. The age at onset ranged between 3 and 6 years. Clinical features included motor deterioration, loss of speech, seizures, and delayed psychomotor development. Most had coarse facial features and hypertrichosis; variable but common additional features included sleep difficulties, kyphoscoliosis, hearing loss, and dysphagia. Biochemical Features The lysosomal-membrane enzyme deficient in MPS IIIC catalyzes the transfer of an acetyl group from cytoplasmic acetyl-CoA to terminal alpha-glucosamine residues of heparan sulfate with lysosomes. It was the first nonhydrolytic activity identified as occurring in lysosomes. Bame and Rome (1985) found that the enzyme carries out a transmembrane acetylation via a ping-pong mechanism. The reaction can be dissected into 2 half reactions: acetylation of the enzyme and transfer of the acetyl group to glucosamine. Bame and Rome (1986) found that 5 cell lines from 3 affected families with Sanfilippo syndrome type C living in the Netherlands were able to catalyze acetylation of the lysosomal membrane and to carry out acetyl-CoA/CoA exchange, but could not transfer the bound acetyl group to glucosamine; a sixth cell line from a patient of Italian ancestry was devoid of this activity. Acetylation of terminal alpha-linked glucosamine residues inside the lysosome is a required step in the degradation of heparan sulfate. Although acetyl-CoA is the acetyl donor in this reaction, it is unlikely that this cofactor could exist stably in the acidic and hydrolytic ambience of the lysosome. N-acetyltransferase provides a means for cells to use cytoplasmically derived acetyl-CoA in heparan sulfate degradation without transporting the intact molecule across the lysosomal membrane. Vectorial transport of the acetyl group across the lysosomal membrane appears to be a unique solution to a complex enzymatic and compartmental problem. Whether the 2 classes of mutants are allelic remains to be determined. The data are consistent with a model assuming a single subunit (Rome, 1986). Diagnosis Klein et al. (1981) described an assay for the detection in leukocytes of homozygous and heterozygous carriers of Sanfilippo syndrome type C. Affected individuals had no residual activity of acetyl-CoA:alpha-glucosaminide N-acetyltransferase. The authors noted that the enzyme was strongly membrane-bound. ### Prenatal Diagnosis DiNatale et al. (1987) diagnosed MPS IIIC in a fetus by enzymatic studies of chorionic villus biopsy material obtained at 10 weeks' gestation. Inheritance MPS IIIC is an autosomal recessive disorder (Fan et al., 2006). Mapping Ausseil et al. (2004) performed a genomewide scan on 44 MPS IIIC patients and their unaffected relatives from 31 families in 10 countries. Several of the families were consanguineous. Analysis of excess homozygosity in patients and identity in state of genotypes among affected relatives identified chromosome 8. Linkage analysis delineated an 8.3-cM candidate gene interval in the pericentromeric region of chromosome 8 (maximum multipoint lod score of 10.61 at marker D8S519). Affected sibs were identical in state for 15 consecutive markers in this region. Molecular Genetics Fan et al. (2006) identified the HGSNAT gene (610453), encoding the human N-acetyltransferase, and identified 2 mutations accounting for 4 alleles in 2 human MPS IIIC cell lines. A splice junction mutation (610453.0001) accounted for 3 mutant alleles, and a single-basepair insertion (610453.0002) accounted for the fourth. Hrebicek et al. (2006) narrowed the candidate linkage region for Sanfilippo syndrome type C to a 2.6-cM interval between D8S1051 and D8S1831 on chromosome 8p and identified causative mutations in the HGSNAT gene (e.g., 610453.0003-610453.0005). Among 30 probands with MPS IIIC, they identified 4 nonsense mutations, 3 frameshift mutations due to deletions or a duplication, 6 splice site mutations, and 14 missense mutations. The probands were geographically and ethnically diverse. In 23 of the 30 probands included in this study for mutation analysis, HGSNAT mutations were identified in both alleles. Five probands were heterozygous for a missense mutation, with a second mutation yet to be identified. In 2 probands, no mutation in the coding regions or immediate flanking regions was identified. These patients were homozygous for the microsatellite markers throughout the entire MPS IIIC locus and may be homozygous for a yet to be identified HGSNAT mutation. Functional expression of human HGSNAT and the mouse ortholog demonstrated that it is the gene that encodes the lysosomal N-acetyltransferase and suggested that this enzyme belongs to a new structural class of proteins that transport the activated acetyl residues across the cell membrane. In 3 unrelated Portuguese patients with MPS IIIC, Coutinho et al. (2008) identified 2 different mutations in the HGSNAT gene (610453.0006 and 610453.0007). Feldhammer et al. (2009) stated that 50 pathogenic mutations in the HGSNAT gene had been reported to date, and the authors identified 10 novel mutations. A review of published mutations showed that they span the entire HGSNAT gene, and there were no obvious genotype/phenotype correlations. Canals et al. (2011) identified 9 different pathogenic mutations in the HGSNAT gene, including 7 novel mutations, in 11 patients with MPS IIIC, including 7 of Spanish origin, 1 from Argentina, and 3 from Morocco. The most common mutation was 372-2A-G (610453.0007), which was found in 4 Spanish patients, with a frequency of 50% (7 of 14 alleles) for the Spanish patients. The second most common mutation was 234+1G-A (610453.0010), which was found in 1 Spanish and 2 Moroccan patients. Haplotype analysis indicated a founder effect for both of these mutations. Each of the 7 novel mutations was found in only 1 patient. In vitro functional expression assays in COS-7 cells showed that missense mutations had practically no residual enzyme activity (range, 0-1.19%). Population Genetics Using multiple ascertainment sources, Nelson et al. (2003) obtained an incidence rate for Sanfilippo syndrome (all forms combined) in western Australia for the period 1969 to 1996 of approximately 1 in 58,000 live births; there was a total of 11 cases, including 5 of type A, 5 of type B, and 1 of type C. Ruijter et al. (2008) reported a high frequency of 2 HGSNAT mutations in the Dutch population (R344C; 610453.0008 and S518F; 610453.0009), which occurred in 22% and 29.3% of mutant alleles, respectively. The birth prevalence of MPS IIIC in Australia, Portugal, and the Netherlands has been estimated at 0.07, 0.12, and 0.21 per 100,000, respectively (Feldhammer et al., 2009). History Zaremba et al. (1992) identified a presumably balanced Robertsonian translocation in 2 sibs with Sanfilippo disease type IIIC and suggested that the mutant gene was located in the pericentric region of either chromosome 14 or chromosome 21. The mother had the same balanced Robertsonian translocation involving chromosomes 14 and 21. A third, unaffected, child did not receive the translocation chromosome from the mother. Zaremba et al. (1992) raised the possibility that one of the 2 mutated loci necessary for the disorder was the result of rearrangement in the pericentric region of either chromosome 14 or 21 and that only the father was a carrier of the 'regular' mutation. INHERITANCE \- Autosomal recessive GROWTH Other \- Usually normal stature HEAD & NECK Face \- Coarse facies, mild Ears \- Hearing loss \- Thickening of the helices Eyes \- Clear corneas \- Synophrys \- Retinitis pigmentosa (late-onset) Nose \- Fleshy nasal tip Mouth \- Everted lower lip CARDIOVASCULAR Heart \- Asymmetric septal hypertrophy RESPIRATORY Nasopharynx \- Frequent upper respiratory infections CHEST Ribs Sternum Clavicles & Scapulae \- Thickened ribs ABDOMEN Liver \- Mild hepatomegaly Spleen \- Mild splenomegaly Gastrointestinal \- Diarrhea \- Dysphagia SKELETAL \- Mild dysostosis multiplex Skull \- Dense calvaria \- Dolichocephaly Spine \- Ovoid thoracolumbar vertebrae \- Kyphoscoliosis Limbs \- Mild joint stiffness SKIN, NAILS, & HAIR Hair \- Synophrys \- Hirsutism \- Coarse hair MUSCLE, SOFT TISSUES \- Hernias NEUROLOGIC Central Nervous System \- Mental retardation \- Slowing mental development by 1.5 to 3 years of age \- Sleep disturbances common \- Loss of speech development \- Motor deterioration \- Seizures Behavioral Psychiatric Manifestations \- Severe behavioral problems at age 3-4 \- Hyperactivity \- Temper tantrums LABORATORY ABNORMALITIES \- Acetyl CoA:alpha-glucosaminidase N-acetyltransferase deficiency in fibroblasts \- Heparan sulfate excretion in urine \- Metachromasia of white blood cells and fibroblasts \- Enzyme replacement therapy has not been effective MISCELLANEOUS \- Variable severity \- Most patients appear unaffected in the first year of life \- Intellectual regression and loss of speech precede the onset of motor retardation by more than 10 years \- Mean age of death is 34 years \- Four clinically indistinguishable biochemically distinct forms MOLECULAR BASIS \- Caused by mutation in the heparan-alpha-glucosaminide N-acetyltransferase gene (HGSNAT, 610453.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	MUCOPOLYSACCHARIDOSIS, TYPE IIIC	c0086649	25,662	omim	https://www.omim.org/entry/252930	2019-09-22T16:24:56	{"doid": ["12801"], "mesh": ["D009084"], "omim": ["252930"], "icd-10": ["E76.22"], "orphanet": ["79271", "581"], "synonyms": ["Alternative titles", "MPS IIIC", "SANFILIPPO SYNDROME C", "ACETYL-CoA:ALPHA-GLUCOSAMINIDE N-ACETYLTRANSFERASE DEFICIENCY"]}
Transthyretin amyloidosis is a slowly progressive condition characterized by the buildup of abnormal deposits of a protein called amyloid (amyloidosis) in the body's organs and tissues. These protein deposits most frequently occur in the peripheral nervous system, which is made up of nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound. Protein deposits in these nerves result in a loss of sensation in the extremities (peripheral neuropathy). The autonomic nervous system, which controls involuntary body functions such as blood pressure, heart rate, and digestion, may also be affected by amyloidosis. In some cases, the brain and spinal cord (central nervous system) are affected. Other areas of amyloidosis include the heart, kidneys, eyes, and gastrointestinal tract. The age at which symptoms begin to develop varies widely among individuals with this condition, and is typically between ages 20 and 70. There are three major forms of transthyretin amyloidosis, which are distinguished by their symptoms and the body systems they affect. The neuropathic form of transthyretin amyloidosis primarily affects the peripheral and autonomic nervous systems, resulting in peripheral neuropathy and difficulty controlling bodily functions. Impairments in bodily functions can include sexual impotence, diarrhea, constipation, problems with urination, and a sharp drop in blood pressure upon standing (orthostatic hypotension). Some people experience heart and kidney problems as well. Various eye problems may occur, such as cloudiness of the clear gel that fills the eyeball (vitreous opacity), dry eyes, increased pressure in the eyes (glaucoma), or pupils with an irregular or "scalloped" appearance. Some people with this form of transthyretin amyloidosis develop carpal tunnel syndrome, which is characterized by numbness, tingling, and weakness in the hands and fingers. The leptomeningeal form of transthyretin amyloidosis primarily affects the central nervous system. In people with this form, amyloidosis occurs in the leptomeninges, which are two thin layers of tissue that cover the brain and spinal cord. A buildup of protein in this tissue can cause stroke and bleeding in the brain, an accumulation of fluid in the brain (hydrocephalus), difficulty coordinating movements (ataxia), muscle stiffness and weakness (spastic paralysis), seizures, and loss of intellectual function (dementia). Eye problems similar to those in the neuropathic form may also occur. When people with leptomeningeal transthyretin amyloidosis have associated eye problems, they are said to have the oculoleptomeningeal form. The cardiac form of transthyretin amyloidosis affects the heart. People with cardiac amyloidosis may have an abnormal heartbeat (arrhythmia), an enlarged heart (cardiomegaly), or orthostatic hypertension. These abnormalities can lead to progressive heart failure and death. Occasionally, people with the cardiac form of transthyretin amyloidosis have mild peripheral neuropathy. ## Frequency The exact incidence of transthyretin amyloidosis is unknown. In northern Portugal, the incidence of this condition is thought to be one in 538 people. Transthyretin amyloidosis is less common among Americans of European descent, where it is estimated to affect one in 100,000 people. The cardiac form of transthyretin amyloidosis is more common among people with African ancestry. It is estimated that this form affects between 3 percent and 3.9 percent of African Americans and approximately 5 percent of people in some areas of West Africa. ## Causes Mutations in the TTR gene cause transthyretin amyloidosis. The TTR gene provides instructions for producing a protein called transthyretin. Transthyretin transports vitamin A (retinol) and a hormone called thyroxine throughout the body. To transport retinol and thyroxine, four transthyretin proteins must be attached (bound) to each other to form a four-protein unit (tetramer). Transthyretin is produced primarily in the liver. A small amount of this protein is produced in an area of the brain called the choroid plexus and in the light-sensitive tissue that lines the back of the eye (the retina). TTR gene mutations are thought to alter the structure of transthyretin, impairing its ability to bind to other transthyretin proteins and altering its normal function. ### Learn more about the gene associated with Transthyretin amyloidosis * TTR ## Inheritance Pattern This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the mutation from one affected parent. Rarely, cases result from new mutations in the gene and occur in people with no history of the disorder in their family. Not all people who have a TTR gene mutation will develop transthyretin amyloidosis. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Transthyretin amyloidosis	c2751492	25,663	medlineplus	https://medlineplus.gov/genetics/condition/transthyretin-amyloidosis/	2021-01-27T08:24:37	{"gard": ["656", "6611"], "mesh": ["C567782"], "omim": ["105210"], "synonyms": []}
A number sign (#) is used with this entry because of evidence that paroxysmal nonkinesigenic dyskinesia-3 with or without generalized epilepsy (PNKD3) is caused by heterozygous mutation in the KCNMA1 gene (600150) on chromosome 10q22. For a discussion of genetic heterogeneity of paroxysmal nonkinesigenic dyskinesia, see PNKD1 (118800). Clinical Features The coexistence of epilepsy and paroxysmal dyskinesia in the same individual or family had been described by Guerrini (2001), Guerrini et al. (2002), and others. Du et al. (2005) studied a large family of European descent with the combination of generalized epilepsy and paroxysmal dyskinesia (GEPD). Among 16 affected individuals, 4 developed isolated epileptic seizures, 7 had isolated paroxysmal nonkinesigenic dyskinesia, and 5 had both phenotypes. All patients except 1 had onset of symptoms in infancy or early childhood; 1 patient with isolated PNKD had onset in the early teens. Most patients had absence seizures, although 2 also had generalized tonic-clonic seizures. Interictal electroencephalography (EEG) showed generalized spike-wave complexes. ### Clinical Variability Zhang et al. (2015) reported 2 unrelated Chinese boys who presented with isolated paroxysmal nonkinesigenic dystonia in infancy. The clinical courses varied somewhat. One child first presented at 20 days of age, and the episodes lasted several minutes to 30 minutes. The episodes occurred once a week initially and 2 to 7 times per day after 1 year, and they were sometimes associated with nystagmus and strabismus. This patient also had sudden decreases in voluntary movement with hypotonia, occasional esotropia, and yawning, lasting as long as 1 hour and occurring once or twice a day. Medication was not beneficial. This patient had severe developmental delay, with sitting at almost 2 years of age and poor understanding of language. The second patient had onset of PNKD at age 7 months. The episodes lasted seconds to minutes and occurred 3 to 5 times a day to once per week. The episodes could be controlled by clonazepam. He had mild developmental delay and poor school performance later in childhood. Triggers of the episodes were not observed in either patient, and ictal and interictal EEG was normal in both patients, excluding a diagnosis of epilepsy, although Zhang et al. (2015) noted that the likelihood of these patients developing later-onset epilepsy could not be ruled out. Brain imaging in both patients was also normal. All parents were unaffected. Inheritance The transmission pattern of PNKD3 in the family reported by Du et al. (2005) was consistent with autosomal dominant inheritance. Mapping By genomewide linkage scan in a large 5-generation family of mixed European descent, Du et al. (2005) demonstrated a locus on 10q22 and narrowed the disease-associated interval to a region of 8.4 cM. The 10q22 locus associated with GEPD contained 40 genes. Molecular Genetics In all 13 affected members of a family with PNKD3, Du et al. (2005) identified a heterozygous missense mutation in the KCNMA1 gene (D434G; 600150.0001). Du et al. (2005) showed that the D434G mutant BK channel had a markedly greater macroscopic current. Single-channel recordings showed an increase in open-channel probability due to a 3- to 5-fold increase in Ca(2+) sensitivity. The authors proposed that enhancement of BK channels in vivo leads to increased excitability by inducing rapid repolarization of action potentials, resulting in generalized epilepsy and paroxysmal dyskinesia by allowing neurons to fire at a faster rate. The study suggested that BK channel-blocking agents might be used in therapy for epilepsy and paroxysmal dyskinesia. In 2 unrelated Chinese boys with isolated PNKD3 and developmental delay but without seizures, Zhang et al. (2015) identified de novo heterozygous missense mutations in the KCNMA1 gene (E884K, 600150.0002 and N1053S, 600150.0003). The mutations were found by candidate gene screening and confirmed by Sanger sequencing. Functional studies of the variants and studies of patient cells were not performed. INHERITANCE \- Autosomal dominant MUSCLE, SOFT TISSUES \- Hypotonia (in some patients) NEUROLOGIC Central Nervous System \- Delayed development (in some patients) \- Seizures, absence (in some patients) \- Seizures, generalized tonic-clonic (in some patients) \- Paroxysmal nonkinesigenic dyskinesia \- Involuntary dystonic or choreiform movements \- Interictal EEG shows 3-4 Hz general spike-wave complexes MISCELLANEOUS \- Patients may have seizures only, dyskinesia only, or both \- Onset usually in childhood (range 6 months to 16 years) \- Dyskinesia may be precipitated by alcohol, stress, or fatigue \- De novo mutation (in some patients) MOLECULAR BASIS \- Caused by mutation in the calcium-activated large conductance potassium channel subfamily M, alpha member 1 gene (KCNMA1, 600150.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	PAROXYSMAL NONKINESIGENIC DYSKINESIA, 3, WITH OR WITHOUT GENERALIZED EPILEPSY	c1836173	25,664	omim	https://www.omim.org/entry/609446	2019-09-22T16:06:03	{"mesh": ["C563719"], "omim": ["609446"], "orphanet": ["79137"], "synonyms": ["Alternative titles", "GENERALIZED EPILEPSY AND PAROXYSMAL DYSKINESIA"]}
Peroxisomal acyl-CoA oxidase deficiency is a disorder that causes deterioration of nervous system functions (neurodegeneration) beginning in infancy. Newborns with peroxisomal acyl-CoA oxidase deficiency have weak muscle tone (hypotonia) and seizures. They may have unusual facial features, including widely spaced eyes (hypertelorism), a low nasal bridge, and low-set ears. Extra fingers or toes (polydactyly) or an enlarged liver (hepatomegaly) also occur in some affected individuals. Most babies with peroxisomal acyl-CoA oxidase deficiency learn to walk and begin speaking, but they experience a gradual loss of these skills (developmental regression), usually beginning between the ages of 1 and 3. As the condition gets worse, affected children develop exaggerated reflexes (hyperreflexia), increased muscle tone (hypertonia), more severe and recurrent seizures (epilepsy), and loss of vision and hearing. Most children with peroxisomal acyl-CoA oxidase deficiency do not survive past early childhood. ## Frequency Peroxisomal acyl-CoA oxidase deficiency is a rare disorder. Its prevalence is unknown. Only a few dozen cases have been described in the medical literature. ## Causes Peroxisomal acyl-CoA oxidase deficiency is caused by mutations in the ACOX1 gene, which provides instructions for making an enzyme called peroxisomal straight-chain acyl-CoA oxidase. This enzyme is found in sac-like cell structures (organelles) called peroxisomes, which contain a variety of enzymes that break down many different substances. The peroxisomal straight-chain acyl-CoA oxidase enzyme plays a role in the breakdown of certain fat molecules called very long-chain fatty acids (VLCFAs). Specifically, it is involved in the first step of a process called the peroxisomal fatty acid beta-oxidation pathway. This process shortens the VLCFA molecules by two carbon atoms at a time until the VLCFAs are converted to a molecule called acetyl-CoA, which is transported out of the peroxisomes for reuse by the cell. ACOX1 gene mutations prevent the peroxisomal straight-chain acyl-CoA oxidase enzyme from breaking down VLCFAs efficiently. As a result, these fatty acids accumulate in the body. It is unclear exactly how VLCFA accumulation leads to the specific features of peroxisomal acyl-CoA oxidase deficiency. However, researchers suggest that the abnormal fatty acid accumulation triggers inflammation in the nervous system that leads to the breakdown of myelin, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses. Destruction of myelin leads to a loss of myelin-containing tissue (white matter) in the brain and spinal cord; loss of white matter is described as leukodystrophy. Leukodystrophy is likely involved in the development of the neurological abnormalities that occur in peroxisomal acyl-CoA oxidase deficiency. ### Learn more about the gene associated with Peroxisomal acyl-CoA oxidase deficiency * ACOX1 ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Peroxisomal acyl-CoA oxidase deficiency	c1849678	25,665	medlineplus	https://medlineplus.gov/genetics/condition/peroxisomal-acyl-coa-oxidase-deficiency/	2021-01-27T08:24:50	{"gard": ["4543"], "mesh": ["C536662"], "omim": ["264470"], "synonyms": []}
Polycythaemia vera Other namesPolycythaemia vera (PV, PCV), erythremia, primary polycythemia, Vaquez disease, Osler-Vaquez disease, polycythemia rubra vera[1] Blood smear from a patient with polycythemia vera SpecialtyOncology Polycythemia vera is an uncommon myeloproliferative neoplasm in which the bone marrow makes too many red blood cells.[1] It may also result in the overproduction of white blood cells and platelets. Most of the health concerns associated with polycythemia vera are caused by the blood being thicker as a result of the increased red blood cells. It is more common in the elderly and may be symptomatic or asymptomatic. Common signs and symptoms include itching (pruritus), and severe burning pain in the hands or feet that is usually accompanied by a reddish or bluish coloration of the skin. Patients with polycythemia vera are more likely to have gouty arthritis. Treatment consists primarily of phlebotomy. ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 3 Diagnosis * 4 Treatment * 5 Epidemiology * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] Erythromelalgia is a rare symptom of PV, here present in a patient with longstanding polycythemia vera. Note reddish limbs and swelling. People with polycythemia vera can be asymptomatic.[2] A classic symptom of polycythemia vera is pruritus or itching, particularly after exposure to warm water (such as when taking a bath),[3] which may be due to abnormal histamine release[4][5] or prostaglandin production.[6] Such itching is present in approximately 40% of patients with polycythemia vera.[7] Gouty arthritis may be present in up to 20% of patients.[7] Peptic ulcer disease is also common in patients with polycythemia vera; most likely due to increased histamine from mast cells, but may be related to an increased susceptibility to infection with the ulcer-causing bacterium H. pylori.[8] Another possible mechanism for the development for peptic ulcer is increased histamine release and gastric hyperacidity related with polycythemia vera. A classic symptom of polycythemia vera (and the related myeloproliferative disease essential thrombocythemia) is erythromelalgia.[9] This is a burning pain in the hands or feet, usually accompanied by a reddish or bluish coloration of the skin. Erythromelalgia is caused by an increased platelet count or increased platelet "stickiness" (aggregation), resulting in the formation of tiny blood clots in the vessels of the extremity; it responds rapidly to treatment with aspirin.[10][11] Patients with polycythemia vera are prone to the development of blood clots (thrombosis). A major thrombotic complication (e.g. heart attack, stroke, deep venous thrombosis, or Budd-Chiari syndrome) may sometimes be the first symptom or indication that a person has polycythemia vera. Headaches, lack of concentration and fatigue are common symptoms that occur in patients with polycythemia vera as well.[citation needed] ## Pathophysiology[edit] Polycythemia vera (PCV), being a primary polycythemia, is caused by neoplastic proliferation and maturation of erythroid, megakaryocytic and granulocytic elements to produce what is referred to as panmyelosis. In contrast to secondary polycythemias, PCV is associated with a low serum level of the hormone erythropoietin (EPO). Instead, PCV cells often carry activating mutation in the tyrosine kinase (JAK2) gene, which acts in signaling pathways of the EPO-receptor, making those cells proliferate independent from EPO.[12] ## Diagnosis[edit] Physical exam findings are non-specific, but may include enlarged liver or spleen, plethora, or gouty nodules. The diagnosis is often suspected on the basis of laboratory tests. Common findings include an elevated hemoglobin level and hematocrit, reflecting the increased number of red blood cells; the platelet count or white blood cell count may also be increased. The erythrocyte sedimentation rate (ESR) is decreased due to an increase in zeta potential. Because polycythemia vera results from an essential increase in erythrocyte production, patients have normal blood oxygenation and a low erythropoietin (EPO) level. In primary polycythemia, there may be 8 to 9 million and occasionally 11 million erythrocytes per cubic millimeter of blood (a normal range for adults is 4-6), and the hematocrit may be as high as 70 to 80%. In addition, the total blood volume sometimes increases to as much as twice normal. The entire vascular system can become markedly engorged with blood, and circulation times for blood throughout the body can increase up to twice the normal value. The increased numbers of erythrocytes can cause the viscosity of the blood to increase as much as five times normal. Capillaries can become plugged by the very viscous blood, and the flow of blood through the vessels tends to be extremely sluggish. As a consequence of the above, people with untreated polycythemia vera are at a risk of various thrombotic events (deep venous thrombosis, pulmonary embolism), heart attack and stroke, and have a substantial risk of Budd-Chiari syndrome (hepatic vein thrombosis),[13] or myelofibrosis. The condition is considered chronic; no cure exists. Symptomatic treatment (see below) can normalize the blood count and most patients can live a normal life for years. The disease appears more common in Jews of European extraction than in most non-Jewish populations. Some familial forms of polycythemia vera are noted, but the mode of inheritance is not clear. A mutation in the JAK2 kinase (V617F) is strongly associated with polycythemia vera.[14][15] JAK2 is a member of the Janus kinase family and makes the erythroid precursors hypersensitive to erythropoietin (EPO). This mutation may be helpful in making a diagnosis or as a target for future therapy. Following history and examination, the British Committee for Standards in Haematology (BCSH) recommend the following tests are performed: * full blood count/film (raised haematocrit; neutrophils, basophils, platelets raised in half of patients) * JAK2 mutation * serum ferritin * renal and liver function tests If the JAK2 mutation is negative and there is no obvious secondary causes the BCSH suggest the following tests: * red cell mass * arterial oxygen saturation * abdominal ultrasound * serum erythropoietin level * bone marrow aspirate and trephine * cytogenetic analysis * erythroid burst-forming unit (BFU-E) culture Other features that may be seen in polycythemia vera include a low ESR and a raised leukocyte alkaline phosphatase. The diagnostic criteria for polycythemia vera have recently been updated by the BCSH. This replaces the previous Polycythemia Vera Study Group criteria. JAK2-positive polycythaemia vera - diagnosis requires both criteria to be present: Criteria Notes A1 High erythrocyte volume fraction (EVF or haematocrit) (>0.52 in men, >0.48 in women) OR raised red cell mass (>25% above predicted) A2 Mutation in JAK2 JAK2-negative polycythemia vera - diagnosis requires A1 + A2 + A3 + either another A or two B criteria: Criteria Notes A1 Raised red cell mass (>25% above predicted) OR haematocrit >0.60 in men, >0.56 in women A2 Absence of mutation in JAK2 A3 No cause of secondary erythrocytosis A4 Palpable splenomegaly A5 Presence of an acquired genetic abnormality (excluding BCR-ABL) in the haematopoietic cells B1 Thrombocytosis (platelet count >450 * 109/l) B2 Neutrophil leucocytosis (neutrophil count > 10 * 109/l in non-smokers; > 12.5109/l in smokers) B3 Radiological evidence of splenomegaly B4 Endogenous erythroid colonies or low serum erythropoietin ## Treatment[edit] Untreated, polycythemia vera can be fatal.[16][17] Research has found that the "1.5-3 years of median survival in the absence of therapy has been extended to at least 10-20 years because of new therapeutic tools."[18] As the condition cannot be cured, treatment focuses on treating symptoms and reducing thrombotic complications by reducing the erythrocyte levels. Phlebotomy is one form of treatment, which often may be combined with other therapies. The removal of blood from the body induces iron deficiency, thereby decreasing the haemoglobin / hematocrit level, and reducing the risk of blood clots. Phlebotomy is typically performed to bring their hematocrit (red blood cell percentage) down below 45 for men or 42 for women.[19] It has been observed that phlebotomy also reduces cognitive impairment (improves cognition).[20] Low dose aspirin (75–81 mg daily) is often prescribed. Research has shown that aspirin reduces the risk for various thrombotic complications. Chemotherapy for polycythemia may be used, either for maintenance, or when the rate of bloodlettings required to maintain normal hematocrit is not acceptable, or when there is significant thrombocytosis or intractable pruritus. This is usually with a "cytoreductive agent" (hydroxyurea, also known as hydroxycarbamide). The tendency of some practitioners to avoid chemotherapy if possible, especially in young patients, is a result of research indicating possible increased risk of transformation to acute myelogenous leukemia (AML). While hydroxyurea is considered safer in this aspect, there is still some debate about its long-term safety.[21] In the past, injection of radioactive isotopes (principally phosphorus-32) was used as another means to suppress the bone marrow. Such treatment is now avoided due to a high rate of AML transformation. Other therapies include interferon injections, and in cases where secondary thrombocytosis (high platelet count) is present, anagrelide may be prescribed. Bone marrow transplants are rarely undertaken in people with polycythemia; since this condition is non-fatal if treated and monitored, the benefits rarely outweigh the risks involved in such a procedure. There are indications that with certain genetic markers, erlotinib may be an additional treatment option for this condition.[22] The JAK2 inhibitor, ruxolitinib, is also used to treat polycythemia.[23] ## Epidemiology[edit] Polycythemia vera occurs in all age groups,[24] although the incidence increases with age. One study found the median age at diagnosis to be 60 years,[7] while a Mayo Clinic study in Olmsted County, Minnesota found that the highest incidence was in people aged 70–79 years.[25] The overall incidence in the Minnesota population was 1.9 per 100,000 person-years, and the disease was more common in men than women.[25] A cluster around a toxic site was confirmed in northeast Pennsylvania in 2008. [26] ## See also[edit] Capillary leak syndrome * Hematopoietic ulcer ## References[edit] 1. ^ a b "polycythemia vera." at Encyclopædia Britannica. 2010\. Encyclopædia Britannica Online. 21 Sep. 2010 2. ^ [Polycythemia vera EBSCO database] verified by URAC; accessed from Mount Sinai Hospital, New York 3. ^ Saini KS, Patnaik MM, Tefferi A (2010). "Polycythemia vera-associated pruritus and its management". Eur J Clin Invest. 40 (9): 828–34. doi:10.1111/j.1365-2362.2010.02334.x. PMID 20597963. 4. ^ Steinman H, Kobza-Black A, Lotti T, Brunetti L, Panconesi E, Greaves M (1987). "Polycythaemia rubra vera and water-induced pruritus: blood histamine levels and cutaneous fibrinolytic activity before and after water challenge". Br J Dermatol. 116 (3): 329–33. doi:10.1111/j.1365-2133.1987.tb05846.x. PMID 3567071. 5. ^ Jackson N, Burt D, Crocker J, Boughton B (1987). "Skin mast cells in polycythaemia vera: relationship to the pathogenesis and treatment of pruritus". Br J Dermatol. 116 (1): 21–9. doi:10.1111/j.1365-2133.1987.tb05787.x. PMID 3814512. 6. ^ Fjellner B, Hägermark O (1979). "Pruritus in polycythemia vera: treatment with aspirin and possibility of platelet involvement". Acta Derm Venereol. 59 (6): 505–12. PMID 94209. 7. ^ a b c Berlin NI (1975). "Diagnosis and classification of polycythemias". Semin Hematol. 12 (4): 339–51. PMID 1198126. 8. ^ Torgano G, Mandelli C, Massaro P, Abbiati C, Ponzetto A, Bertinieri G, Bogetto S, Terruzzi E, de Franchis R (2002). "Gastroduodenal lesions in polycythaemia vera: frequency and role of Helicobacter pylori". Br J Haematol. 117 (1): 198–202. doi:10.1046/j.1365-2141.2002.03380.x. PMID 11918555. 9. ^ van Genderen P, Michiels J (1997). "Erythromelalgia: a pathognomonic microvascular thrombotic complication in essential thrombocythemia and polycythemia vera". Semin Thromb Hemost. 23 (4): 357–63. doi:10.1055/s-2007-996109. PMID 9263352. 10. ^ Michiels J (1997). "Erythromelalgia and vascular complications in polycythemia vera". Semin Thromb Hemost. 23 (5): 441–54. doi:10.1055/s-2007-996121. PMID 9387203. 11. ^ Landolfi R, Ciabattoni G, Patrignani P, Castellana M, Pogliani E, Bizzi B, Patrono C (1992). "Increased thromboxane biosynthesis in patients with polycythemia vera: evidence for aspirin-suppressible platelet activation in vivo". Blood. 80 (8): 1965–71. doi:10.1182/blood.V80.8.1965.1965. PMID 1327286. 12. ^ Kumar, et al.: Robbin's Basic Pathology, 8th edition, Saunders, 2007 13. ^ Thurmes PJ, Steensma DP (July 2006). "Elevated serum erythropoietin levels in patients with Budd-Chiari syndrome secondary to polycythemia vera: clinical implications for the role of JAK2 mutation analysis". Eur. J. Haematol. 77 (1): 57–60. doi:10.1111/j.1600-0609.2006.00667.x. PMID 16827884. 14. ^ Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S, Vassiliou GS, Bench AJ, Boyd EM, Curtin N, Scott MA, Erber WN, Green AR (2005). "Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders". Lancet. 365 (9464): 1054–61. doi:10.1016/S0140-6736(05)71142-9. PMID 15781101. S2CID 24419497. 15. ^ Levine RL, Wadleigh M, Cools J, Ebert BL, Wernig G, Huntly BJ, Boggon TJ, Wlodarska I, Clark JJ, Moore S, Adelsperger J, Koo S, Lee JC, Gabriel S, Mercher T, D'Andrea A, Frohling S, Dohner K, Marynen P, Vandenberghe P, Mesa RA, Tefferi A, Griffin JD, Eck MJ, Sellers WR, Meyerson M, Golub TR, Lee SJ, Gilliland DG (2005). "Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis". Cancer Cell. 7 (4): 387–97. doi:10.1016/j.ccr.2005.03.023. PMID 15837627. 16. ^ Mayo Clinic staff. "Polycythemia vera - MayoClinic.com". Polycythemia vera: Definition. Mayo Clinic. Retrieved 2011-09-03. 17. ^ "What Is Polycythemia Vera?". National Heart, Lung and Blood Institute. Retrieved 2011-09-03. 18. ^ "Polycythemia Vera Follow-up". Retrieved 2011-09-03. 19. ^ Streiff MB, Smith B, Spivak JL (2002). "The diagnosis and management of polycythemia vera in the era since the Polycythemia Vera Study Group: a survey of American Society of Hematology members' practice patterns". Blood. 99 (4): 1144–9. doi:10.1182/blood.V99.4.1144. PMID 11830459. 20. ^ Di Pollina L, Mulligan R, Juillerat Van der Linden A, Michel JP, Gold G (2000). "Cognitive impairment in polycythemia vera: partial reversibility upon lowering of the hematocrit". Eur. Neurol. 44 (1): 57–9. doi:10.1159/000008194. PMID 10894997. S2CID 40928145. 21. ^ Björkholm, M; Derolf, AR; Hultcrantz, M; et al. (10 June 2011). "Treatment-related risk factors for transformation to acute myeloid leukemia and myelodysplastic syndromes in myeloproliferative neoplasms". Journal of Clinical Oncology. 29 (17): 2410–5. doi:10.1200/JCO.2011.34.7542. PMC 3107755. PMID 21537037. 22. ^ Li Z, Xu M, Xing S, Ho W, Ishii T, Li Q, Fu X, Zhao Z (2007). "Erlotinib Effectively Inhibits JAK2V617F Activity and Polycythemia Vera Cell Growth". J Biol Chem. 282 (6): 3428–32. doi:10.1074/jbc.C600277200. PMC 2096634. PMID 17178722. 23. ^ Tefferi, A; Vannucchi, AM; Barbui, T (10 January 2018). "Polycythemia vera treatment algorithm 2018". Blood Cancer Journal. 8 (1): 3. doi:10.1038/s41408-017-0042-7. PMC 5802495. PMID 29321547. 24. ^ Passamonti F, Malabarba L, Orlandi E, Baratè C, Canevari A, Brusamolino E, Bonfichi M, Arcaini L, Caberlon S, Pascutto C, Lazzarino M (2003). "Polycythemia vera in young patients: a study on the long-term risk of thrombosis, myelofibrosis and leukemia". Haematologica. 88 (1): 13–8. PMID 12551821. 25. ^ a b Anía B, Suman V, Sobell J, Codd M, Silverstein M, Melton L (1994). "Trends in the incidence of polycythemia vera among Olmsted County, Minnesota residents, 1935-1989". Am J Hematol. 47 (2): 89–93. doi:10.1002/ajh.2830470205. PMID 8092146. 26. ^ MICHAEL RUBINKAM (2008). "Cancer cluster confirmed in northeast Pennsylvania". Associated Press. Archived from the original on September 2, 2008. ## External links[edit] * Voices of MPN: Polycythemia Vera * 11-141d. at Merck Manual of Diagnosis and Therapy Professional Edition Classification D * ICD-10: D45 * ICD-9-CM: 238.4 * ICD-O: M9950/3 * MeSH: D011087 External resources * MedlinePlus: 000589 * v * t * e Myeloid-related hematological malignancy CFU-GM/ and other granulocytes CFU-GM Myelocyte AML: * Acute myeloblastic leukemia * M0 * M1 * M2 * APL/M3 MP * Chronic neutrophilic leukemia Monocyte AML * AMoL/M5 * Myeloid dendritic cell leukemia CML * Philadelphia chromosome * Accelerated phase chronic myelogenous leukemia Myelomonocyte AML * M4 MD-MP * Juvenile myelomonocytic leukemia * Chronic myelomonocytic leukemia Other * Histiocytosis CFU-Baso AML * Acute basophilic CFU-Eos AML * Acute eosinophilic MP * Chronic eosinophilic leukemia/Hypereosinophilic syndrome MEP CFU-Meg MP * Essential thrombocytosis * Acute megakaryoblastic leukemia CFU-E AML * Erythroleukemia/M6 MP * Polycythemia vera MD * Refractory anemia * Refractory anemia with excess of blasts * Chromosome 5q deletion syndrome * Sideroblastic anemia * Paroxysmal nocturnal hemoglobinuria * Refractory cytopenia with multilineage dysplasia CFU-Mast Mastocytoma * Mast cell leukemia * Mast cell sarcoma * Systemic mastocytosis Mastocytosis: * Diffuse cutaneous mastocytosis * Erythrodermic mastocytosis * Adult type of generalized eruption of cutaneous mastocytosis * Urticaria pigmentosa * Mast cell sarcoma * Solitary mastocytoma Systemic mastocytosis * Xanthelasmoidal mastocytosis Multiple/unknown AML * Acute panmyelosis with myelofibrosis * Myeloid sarcoma MP * Myelofibrosis * Acute biphenotypic leukaemia [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Polycythemia vera	c0032463	25,666	wikipedia	https://en.wikipedia.org/wiki/Polycythemia_vera	2021-01-18T19:07:55	{"gard": ["7422"], "mesh": ["D011087"], "umls": ["C0032463"], "orphanet": ["729"], "wikidata": ["Q948318"]}
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. (June 2020) (Learn how and when to remove this template message) Post-stroke depression (PSD) is considered the most frequent and important neuropsychiatric consequence of stroke. Approximately one-third of stroke survivors experience major depression. Moreover, this condition can have an adverse effect on cognitive function, functional recovery and survival. ## Contents * 1 Mechanism * 2 Diagnosis * 2.1 Definition * 3 Prevalence * 4 References * 4.1 Sources ## Mechanism[edit] The scientific community is divided into two “camps” supporting opposing views: some propose a primary biological mechanism with stroke affecting neural circuits involved in mood regulation which in turn causes post-stroke depression, while other researchers claim that post stroke depression is caused by social and psychological stressors that emerge as a result of stroke. While an integrated bio-psycho-social model including both biological and psychosocial aspects of post stroke depression seems warranted, a number of studies clearly suggest that biological mechanisms play a major role in the development of post stroke depression. 1. stroke patients show a higher rate of depression compared to orthopedic patients with disabilities of comparable severity. 2. Several studies proposed an association with specific lesions (left anterior and basal ganglia lesions and lesions close to frontal pole) and occurrence of post stroke depression. 3. Some studies reported an association between post-stroke mania and right orbital frontal, basotemporal, basal ganglia lesions. 4. It has been shown that patients with anosognosia who are unaware of their disability still develop post stroke depression. Despite this evidence, the association of post-stroke depression to specific brain lesions is still vague and needs replication from various independent groups. Furthermore, the cause of post stroke depression at a functional level is not clear. The only biological model was proposed by Robinson and co-workers:[full citation needed] They hypothesized that the depletion of monoaminergic amines occurring after stroke play a role in post stroke-depression. They point out that norepinephrinergic and serotonergic nuclei send projections to the frontal cortex and arc posteriorly, running through the deep layers of the cortex, where they arborize and send terminal projections into the superficial cortical layers. These norepinephrinergic and serotoninergic pathways are disrupted in basal ganglia and frontal lobe lesions – sites that are shown to be associated with post stroke depression. Additionally, depletion in dopamine (due to pallidal lesions) can trigger anhedonia and avolition.[1] However, this model is far from being universally accepted and there are serious objections both to their model and findings showing the association between post-stroke depression and lesion sites.[citation needed] Depression-like behaviors are demonstrated in a mouse model of cortical intracerebral hemorrhage.[2][unreliable medical source] ## Diagnosis[edit] This section relies largely or entirely on a single source. Relevant discussion may be found on the talk page. Please help improve this article by introducing citations to additional sources. Find sources: "Post-stroke depression" – news · newspapers · books · scholar · JSTOR (June 2020) ### Definition[edit] The Diagnostic and Statistical Manual (DSM) IV categorizes post-stroke depression as “mood disorder due to a general medical condition” (i.e. stroke) with the specifiers of depressive features, major depressive-like episodes, manic features, or mixed features.[3] Utilizing patient data from acute hospital admission, community surveys, or out patient clinics previous studies have identified two types of depressive disorders associated with cerebral ischemia: major depression, which occurs in up to 25% of patients; and minor depression, which has been defined for research purposes by DSM-IV criteria as a depressed mood or loss of interest and at least two but fewer than four symptoms of major depression. Minor depression occurs in up to 30% of patients following stroke. ## Prevalence[edit] Prevalence clearly varies over time with an apparent peak 3–6 months after stroke and subsequent decline in prevalence at one-year reaches about to 50% of initial rates. Robinson and colleagues[full citation needed] characterized the natural course of major depression after stroke with spontaneous remission typically 1 to 2 years after stroke. However, it was also noted that in few cases depression becomes chronic and may persist more than 3 years following stroke. On the other hand, minor depression appeared to be more variable, with both short term and long term depression occurring in these patients. Post-stroke depression is highly prevalent among both men and women. However, it appears that post-stroke depression is more common in women when prevalence is compared between the sexes.[4] Women were twice as likely to experience post-stroke depression than men. It is hypothesized, based on CT scanning, that of the two sexes experiencing post-stroke depression, women who had post-stroke depression had a higher rate of left hemisphere lesions than men.[5] However, risk of post-stroke depression can not be determined effectively based on the location of the lesion in the brain and more research in this area is needed.[6] It has also been postulated that the risk of developing post-stroke depression in male patients is partly linked to having a high level of limitations and disability in functioning, especially in performing activities of daily living (ADL's), as a result of their stroke; the greater the limitation, the greater the severity.[5] Risk of developing depression post-stroke in women is partly linked to a history of psychological disorders as well as limitations involving cognition as a result of their stroke.[5] ## References[edit] 1. ^ Miller, Jeffrey M.; Vorel, Stanislav R.; Tranguch, Anthony J.; Kenny, Edward T.; Mazzoni, Pietro; van Gorp, Wilfred G.; Kleber, Herbert D. (May 2006). "Anhedonia After a Selective Bilateral Lesion of the Globus Pallidus" (PDF). American Journal of Psychiatry. 163 (5): 786–788. doi:10.1176/ajp.2006.163.5.786. PMID 16648316. 2. ^ Zhu, Wei; Gao, Yufeng; Chang, Che-Feng; Wan, Jie-Ru; Zhu, Shan-Shan; Wang, Jian (15 May 2014). "Mouse models of intracerebral hemorrhage in ventricle, cortex, and hippocampus by injections of autologous blood or collagenase". PLoS One. 9 (5): e97423. doi:10.1371/journal.pone.0097423. PMC 4022524. PMID 24831292. 3. ^ American Psychiatric Association (1994). Diagnostic and Statistical Manual of Mental Disorders: DSM-IV. Washington DC: American Psychiatric Press.[pages needed] 4. ^ Poynter, Brittany; Shuman, Mira; Diaz-Granados, Natalia; Kapral, Moira; Grace, Sherry L.; Stewart, Donna E. (November 2009). "Sex differences in the prevalence of post-stroke depression: A systematic review". Psychosomatics. 50 (6): 563–569. doi:10.1176/appi.psy.50.6.563. hdl:10315/24309. PMID 19996226. 5. ^ a b c Paradiso, Sergio; Robinson, Robert G. (Winter 1998). "Gender Differences in Poststroke Depression". Journal of Neuropsychiatry and Clinical Neurosciences. 10 (1): 41–47. doi:10.1176/jnp.10.1.41. PMID 9547465. 6. ^ Carson, Alan J.; MacHale, Siobhan; Allen, Kathryn; Lawrie, Stephen M.; Dennis, Martin; House, Allan; Sharpe, Michael (8 July 2000). "Depression after stroke and lesion location: a systematic review". The Lancet. 356 (9224): 122–126. doi:10.1016/S0140-6736(00)02448-X. PMID 10963248. ### Sources[edit] * Gainotti, G; Azzoni, A; Marra, C (August 1999). "Frequency, phenomenology and anatomical-clinical correlates of major post-stroke depression". British Journal of Psychiatry. 175: 163–167. doi:10.1192/bjp.175.2.163. PMID 10627800. * Gainotti, Guido; Marra, Camillo (February 2002). "Determinants and consequences of post stroke depression". Current Opinion in Neurology. 15 (1): 85–89. doi:10.1097/00019052-200202000-00013. PMID 11796955. * Robinson, RG; Starksein, SE (Winter 1990). "Current research in affective disorders following stroke". Journal of Neuropsychiatry and Clinical Neurosciences. 2 (1): 1–14. doi:10.1176/jnp.2.1.1. PMID 2136055. * Robinson, Robert G.; Starr, Lyn Book; Kubos, Kenneth L.; Price, Thomas R. (September 1983). "A Two year longitudinal study of post-stroke mood disorders: findings during the initial evaluation" (pdf). Stroke. 14 (5): 736–744. doi:10.1161/01.str.14.5.736. PMID 6658957. 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[Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Post-stroke depression	None	25,667	wikipedia	https://en.wikipedia.org/wiki/Post-stroke_depression	2021-01-18T18:45:01	{"icd-10": ["F06.3"], "wikidata": ["Q7233752"]}
Endocrine disorder Addison's disease Other namesAddison disease, chronic adrenal insufficiency, hypocortisolism, hypoadrenalism, primary adrenal insufficiency[1] Darkening of the skin seen on the legs of a white person with Addison's disease SpecialtyEndocrinology SymptomsAbdominal pain, weakness, weight loss, darkening of the skin[1] ComplicationsAdrenal crisis[1] Usual onsetMiddle-aged females[1] CausesProblems with the adrenal gland[1] Diagnostic methodBlood tests, urine tests, medical imaging[1] TreatmentSynthetic Corticosteroid such as hydrocortisone and fludrocortisone[1][2] Frequency0.9–1.4 per 10,000 people (developed world)[1][3] DeathsDoubles risk of death Addison's disease, also known as primary adrenal insufficiency and hypocortisolism, is a rare long-term endocrine disorder characterized by inadequate production of the steroid hormones cortisol and aldosterone by the two outer layers of the cells of the adrenal gland (adrenal cortex).[4] Symptoms generally come on slowly and may include abdominal pain and gastrointestinal abnormalities, weakness, and weight loss.[1] Darkening of the skin in certain areas may also occur.[1] Under certain circumstances, an adrenal crisis may occur with low blood pressure, vomiting, lower back pain, and loss of consciousness.[1] Mood changes may also occur. Rapid onset of symptoms indicates acute adrenal failure which is a serious and emergent condition.[4] An adrenal crisis can be triggered by stress, such as from an injury, surgery, or infection.[1] Addison's disease arises from problems with the adrenal gland such that not enough of the steroid hormone cortisol and possibly aldosterone are produced,[1] most often due to damage by the body's own immune system in the developed world and tuberculosis in the developing world.[5] Other causes include certain medications, sepsis, and bleeding into both adrenal glands.[1][5] Secondary adrenal insufficiency is caused by not enough adrenocorticotropic hormone (ACTH) (produced by the pituitary gland) or corticotropin-releasing hormone (CRH) (produced by the hypothalamus).[1] Despite this distinction, adrenal crises can happen in all forms of adrenal insufficiency.[1] Addison's disease is generally diagnosed by blood tests, urine tests, and medical imaging.[1] Addison's disease can be described in association with chronic mucocutaneous candidiais, diabetes mellitus, pernicious anemia, hypogonadism, chronic and active hepatitis, malabsorption, Immunoglobulin abnormalities, alopecia, vitiligo, spontaneous myxedema, Graves Disease, and chronic lymphocytic thyroiditis.[6] Treatment involves replacing the absent hormones.[1] This involves taking a synthetic corticosteroid such as hydrocortisone and fludrocortisone.[1][2] These medications are usually taken by mouth.[1] Lifelong, continuous steroid replacement therapy is required, with regular follow-up treatment and monitoring for other health problems.[7] A high-salt diet may also be useful in some people.[1] If symptoms worsen, an injection of corticosteroid is recommended and people should carry a dose with them.[1] Often, large amounts of intravenous fluids with the sugar dextrose are also required.[1] Without treatment, an adrenal crisis can result in death.[1] Addison's disease affects about 0.9 to 1.4 per 10,000 people in the developed world.[1][3] It occurs most frequently in middle-aged females.[1] Secondary adrenal insufficiency is more prevalent.[3] Long-term outcomes with treatment are typically favorable.[8] It is named after Thomas Addison, a graduate of the University of Edinburgh Medical School, who first described the condition in 1855.[9] The adjective "addisonian" is used to describe features of the condition, as well as people with Addison's disease.[10] ## Contents * 1 Signs and symptoms * 1.1 Adrenal crisis * 2 Causes * 2.1 Adrenal destruction * 2.2 Adrenal dysgenesis * 2.3 Impaired steroidogenesis * 3 Diagnosis * 3.1 Suggestive features * 3.2 Testing * 4 Treatment * 4.1 Maintenance * 4.2 Crisis * 5 Prognosis * 6 Epidemiology * 7 History * 8 Other animals * 9 References * 10 External links ## Signs and symptoms[edit] Hyperpigmentation as seen in a woman with Addison's disease Darkening of the gums due to increased pigment as seen in Addison's disease[11] The symptoms of Addison's disease generally develop gradually.[12] Symptoms may include fatigue, muscle weakness, weight loss, nausea, vomiting, loss of appetite, lightheadedness upon standing, irritability, depression, and diarrhea.[12] Some people have cravings for salty foods due to the loss of sodium through their urine.[10][12] Hyperpigmentation of the skin may be seen, particularly when the person lives in a sunny area, as well as darkening of the palmar crease, sites of friction, recent scars, the vermilion border of the lips, and genital skin.[13] These skin changes are not encountered in secondary and tertiary hypoadrenalism.[14] Skin Changes: * Hyperpigmentation of the skin * Vitiligo Gastrointestinal Changes * Nausea and vomiting * Weight loss * abdominal pain * Less common but still occurring: malnutrition and muscle wasting Behavioral Disorders * Anxiety * Depression * Irritability * Poor Concentration Changes in Females * Loss or irregularity of menstrual cycle * Loss of body hair * decreased sexual drive[4] On physical examination, these clinical signs may be noticed:[10] * Low blood pressure with or without orthostatic hypotension (blood pressure that decreases with standing) * Darkening (hyperpigmentation) of the skin, including areas not exposed to the sun. Characteristic sites of darkening are skin creases (e.g., of the hands), nipple, and the inside of the cheek (buccal mucosa); also, old scars may darken. This occurs because melanocyte-stimulating hormone (MSH) and ACTH share the same precursor molecule, pro-opiomelanocortin (POMC). After production in the anterior pituitary gland, POMC gets cleaved into gamma-MSH, ACTH, and beta-lipotropin. The subunit ACTH undergoes further cleavage to produce alpha-MSH, the most important MSH for skin pigmentation. In secondary and tertiary forms of adrenal insufficiency, skin darkening does not occur, as ACTH is not overproduced. Addison's disease is associated with the development of other autoimmune diseases, such as type I diabetes, thyroid disease (Hashimoto's thyroiditis), celiac disease, or vitiligo.[15][16] Addison's disease may be the only manifestation of undiagnosed celiac disease.[15] Both diseases share the same genetic risk factors (HLA-DQ2 and HLA-DQ8 haplotypes).[17] The presence of Addison's in addition to mucocutaneous candidiasis, hypoparathyroidism, or both, is called autoimmune polyendocrine syndrome type 1.[18] The presence of Addison's in addition to autoimmune thyroid disease, type 1 diabetes, or both, is called autoimmune polyendocrine syndrome type 2.[19] ### Adrenal crisis[edit] Main article: Adrenal crisis An "adrenal crisis" or "addisonian crisis" is a constellation of symptoms that indicates severe adrenal insufficiency. This may be the result of either previously undiagnosed Addison's disease, a disease process suddenly affecting adrenal function (such as adrenal hemorrhage), or an intercurrent problem (e.g., infection, trauma) in someone known to have Addison's disease. It is a medical emergency and potentially life-threatening situation requiring immediate emergency treatment.[citation needed] Characteristic symptoms are:[12] * Sudden penetrating pain in the legs, lower back, or abdomen * Severe vomiting and diarrhea, resulting in dehydration * Low blood pressure * Syncope (loss of consciousness and ability to stand) * Hypoglycemia (reduced level of blood glucose) * Confusion, psychosis, slurred speech * Severe lethargy * Hyponatremia (low sodium level in the blood) * Hyperkalemia (elevated potassium level in the blood) * Hypercalcemia (elevated calcium level in the blood) * Convulsions * Fever ## Causes[edit] The negative feedback loop for glucocorticoids Causes of adrenal insufficiency can be categorized by the mechanism through which they cause the adrenal glands to produce insufficient cortisol. This can be due to damage or destruction of the adrenal cortex. These deficiencies include glucocorticoid and mineralocorticoid hormones as well. These are adrenal dysgenesis (the gland has not formed adequately during development), impaired steroidogenesis (the gland is present but is biochemically unable to produce cortisol), or adrenal destruction (disease processes leading to glandular damage).[10] ### Adrenal destruction[edit] Autoimmune adrenalitis is the most common cause of Addison's disease in the industrialized world. Autoimmune destruction of the adrenal cortex is caused by an immune reaction against the enzyme 21-hydroxylase (a phenomenon first described in 1992).[20] This may be isolated or in the context of autoimmune polyendocrine syndrome (APS type 1 or 2), in which other hormone-producing organs, such as the thyroid and pancreas, may also be affected.[21] Adrenal destruction is also a feature of adrenoleukodystrophy, and when the adrenal glands are involved in metastasis (seeding of cancer cells from elsewhere in the body, especially lung), hemorrhage (e.g., in Waterhouse–Friderichsen syndrome or antiphospholipid syndrome), particular infections (tuberculosis, histoplasmosis, coccidioidomycosis), or the deposition of abnormal protein in amyloidosis.[22] ### Adrenal dysgenesis[edit] All causes in this category are genetic, and generally very rare. These include mutations to the SF1 transcription factor, congenital adrenal hypoplasia due to DAX-1 gene mutations and mutations to the ACTH receptor gene (or related genes, such as in the Triple-A or Allgrove syndrome). DAX-1 mutations may cluster in a syndrome with glycerol kinase deficiency with a number of other symptoms when DAX-1 is deleted together with a number of other genes.[10] ### Impaired steroidogenesis[edit] To form cortisol, the adrenal gland requires cholesterol, which is then converted biochemically into steroid hormones. Interruptions in the delivery of cholesterol include Smith–Lemli–Opitz syndrome and abetalipoproteinemia.[verification needed] Of the synthesis problems, congenital adrenal hyperplasia is the most common (in various forms: 21-hydroxylase, 17α-hydroxylase, 11β-hydroxylase and 3β-hydroxysteroid dehydrogenase), lipoid CAH due to deficiency of StAR and mitochondrial DNA mutations.[10] Some medications interfere with steroid synthesis enzymes (e.g., ketoconazole), while others accelerate the normal breakdown of hormones by the liver (e.g., rifampicin, phenytoin).[10] ## Diagnosis[edit] ### Suggestive features[edit] Routine laboratory investigations may show:[10] * Low blood sugar (worse in children due to loss of glucocorticoid's glucogenic effects) * Low blood sodium, due to loss of production of the hormone aldosterone, to the kidney's inability to excrete free water in the absence of sufficient cortisol, and also the effect of corticotropin-releasing hormone to stimulate secretion of ADH. * High blood potassium, due to loss of production of the hormone aldosterone. * Eosinophilia and lymphocytosis (increased number of eosinophils or lymphocytes, two types of white blood cells) * Metabolic acidosis (increased blood acidity), also is due to loss of the hormone aldosterone because sodium reabsorption in the distal tubule is linked with acid/hydrogen ion (H+) secretion. Absent or insufficient levels of aldosterone stimulation of the renal distal tubule leads to sodium wasting in the urine and H+ retention in the serum. ### Testing[edit] Cortisol Aldosterone In suspected cases of Addison's disease, demonstration of low adrenal hormone levels even after appropriate stimulation (called the ACTH stimulation test or synacthen test) with synthetic pituitary ACTH hormone tetracosactide is needed for the diagnosis. Two tests are performed, the short and the long test. Dexamethasone does not cross-react with the assay and can be administered concomitantly during testing.[citation needed] The short test compares blood cortisol levels before and after 250 micrograms of tetracosactide (intramuscular or intravenous) is given. If, one hour later, plasma cortisol exceeds 170 nmol/l and has risen by at least 330 nmol/l to at least 690 nmol/l, adrenal failure is excluded. If the short test is abnormal, the long test is used to differentiate between primary adrenal insufficiency and secondary adrenocortical insufficiency.[citation needed] The long test uses 1 mg tetracosactide (intramuscular). Blood is taken 1, 4, 8, and 24 hr later. Normal plasma cortisol level should reach 1000 nmol/l by 4 hr. In primary Addison's disease, the cortisol level is reduced at all stages, whereas in secondary corticoadrenal insufficiency, a delayed but normal response is seen.Other tests may be performed to distinguish between various causes of hypoadrenalism, including renin and adrenocorticotropic hormone levels, as well as medical imaging \- usually in the form of ultrasound, computed tomography or magnetic resonance imaging.[citation needed] Adrenoleukodystrophy, and the milder form, adrenomyeloneuropathy, cause adrenal insufficiency combined with neurological symptoms. These diseases are estimated to be the cause of adrenal insufficiency in about 35% of diagnosed male with idiopathic Addison's disease, and should be considered in the differential diagnosis of any male with adrenal insufficiency. Diagnosis is made by a blood test to detect very long chain fatty acids.[23] ## Treatment[edit] ### Maintenance[edit] Treatment for Addison's disease involves replacing the missing cortisol, sometimes in the form of hydrocortisone tablets, or prednisone tablets in a dosing regimen that mimics the physiological concentrations of cortisol. Alternatively, one-quarter as much prednisolone may be used for equal glucocorticoid effect as hydrocortisone. Treatment is usually lifelong. In addition, many people require fludrocortisone as replacement for the missing aldosterone.[citation needed] People with Addison's are often advised to carry information on them (e.g., in the form of a MedicAlert bracelet or information card) for the attention of emergency medical services personnel who might need to attend to their needs.[24][25] It is also recommended that a needle, syringe, and injectable form of cortisol be carried for emergencies.[25] People with Addison's disease are advised to increase their medication during periods of illness or when undergoing surgery or dental treatment.[25] Immediate medical attention is needed when severe infections, vomiting, or diarrhea occur, as these conditions can precipitate an Addisonian crisis. A person who is vomiting may require injections of hydrocortisone instead.[26] Those with low aldosterone levels may also benefit from a high sodium diet. It may also be beneficial for the people with Addison's disease to increase their dietary intake of calcium and vitamin D. High dosages of corticosteroids are linked to osteoporosis so these may be necessary for bone health.[27] Sources of calcium include dairy products, leafy greens and fortified flours among many others. Vitamin D can be obtained through the sun, oily fish, red meat, and egg yolks among many others. Though there are many sources to obtain vitamin D through your diet, many people choose to use a supplement. ### Crisis[edit] Standard therapy involves intravenous injections of glucocorticoids and large volumes of intravenous saline solution with dextrose (glucose). This treatment usually brings rapid improvement. If intravenous access is not immediately available, intramuscular injection of glucocorticoids can be used. When the person can take fluids and medications by mouth, the amount of glucocorticoids is decreased until a maintenance dose is reached. If aldosterone is deficient, maintenance therapy also includes oral doses of fludrocortisone acetate.[28] ## Prognosis[edit] Outcomes are typically good when treated. Most can expect to live relatively normal lives. Someone with the disease should be observant of symptoms of an "Addison's crisis" while the body is strained, as in rigorous exercise or being sick, the latter often needing emergency treatment with intravenous injections to treat the crisis.[29] Individuals with Addison's disease have more than a doubled mortality rate.[30] Furthermore, individuals with Addison's disease and diabetes mellitus have an almost 4 times increase in mortality compared to individuals with only diabetes.[31] The risk ratio for cause mortality in males and females is 2.19 and 2.86 respectively. Death from individuals with Addison's disease often occurs due to cardiovascular disease, infectious disease, and malignant tumors among other possibilities.[32] ## Epidemiology[edit] The frequency rate of Addison's disease in the human population is sometimes estimated at roughly one in 100,000.[33] Some put the number closer to 40–144 cases per million population (1/25,000–1/7,000).[1][34][35] Addison's can affect persons of any age, sex, or ethnicity, but it typically presents in adults between 30 and 50 years of age.[35][36] Research has shown no significant predispositions based on ethnicity.[34] Approximately 70% of Addison's Disease diagnoses occur due to autoimmune reaction which caused damage to the adrenal cortex.[4] ## History[edit] Addison's disease is named after Thomas Addison, the British physician who first described the condition in On the Constitutional and Local Effects of Disease of the Suprarenal Capsules (1855).[37] He originally described it as "melasma suprarenale," but later physicians gave it the medical eponym "Addison's disease" in recognition of Addison's discovery.[38] While the six under Addison in 1855 all had adrenal tuberculosis,[39] the term "Addison's disease" does not imply an underlying disease process. The condition was initially considered a form of anemia associated with the adrenal glands. Because little was known at the time about the adrenal glands (then called "Supra-Renal Capsules"), Addison's monograph describing the condition was an isolated insight. As the adrenal function became better known, Addison's monograph became known as an important medical contribution and a classic example of careful medical observation.[40] Tuberculosis used to be a major cause of Addison's Disease and acute adrenal failure and is still a leading cause in developing countries today.[4] ## Other animals[edit] Main article: Hypoadrenocorticism in dogs Hypoadrenocorticism is uncommon in dogs,[41] and rare in cats, with less than 40 known feline cases worldwide, since first documented in 1983.[42][43] Individual cases have been reported in a grey seal,[44] a red panda,[45] a flying fox,[46] and a sloth.[47] In dogs, hypoadrenocorticism has been diagnosed in many breeds.[41] Vague symptoms which wax and wane can cause delay in recognition of the presence of the disease.[48] Female dogs appear more affected than male dogs, though this may not be the case in all breeds.[48][49] The disease is most often diagnosed in dogs which are young to middle aged, but it can occur at any age from 4 months to 14 years.[48] Treatment of hypoadrenocorticism must replace the hormones (cortisol and aldosterone) which the dog cannot produce itself.[50] This is achieved either by daily treatment with fludrocortisone, or monthly injections with desoxycorticosterone pivalate (DOCP) and daily treatment with a glucocorticoid, such as prednisone.[50] Several follow-up blood tests are required so that the dose can be adjusted until the dog is receiving the correct amount of treatment, because the medications used in the therapy of hypoadrenocorticism can cause excessive thirst and urination if not prescribed at the lowest effective dose.[50] In anticipation of stressful situations, such as staying in a boarding kennel, dogs require an increased dose of prednisone.[50] Lifelong treatment is required, but the prognosis for dogs with hypoadrenocorticism is very good.[48] ## References[edit] 1. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa "Adrenal Insufficiency and Addison's Disease". National Institute of Diabetes and Digestive and Kidney Diseases. May 2014. Archived from the original on 13 March 2016. Retrieved 13 March 2016. 2. ^ a b Napier, Catherine; Pearce, Simon H.S. (June 2014). "Current and emerging therapies for Addison's disease". Current Opinion in Endocrinology, Diabetes and Obesity. Philadelphia, Pennsylvania: Lippincott Williams & Wilkins Ltd. 21 (3): 147–53. doi:10.1097/med.0000000000000067. PMID 24755997. S2CID 13732181. 3. ^ a b c Brandão Neto, RA; de Carvalho, JF (2014). "Diagnosis and classification of Addison's disease (autoimmune adrenalitis)". Autoimmunity Reviews. 13 (4–5): 408–11. doi:10.1016/j.autrev.2014.01.025. PMID 24424183. 4. ^ a b c d e "Addison's Disease". NORD (National Organization for Rare Disorders). Retrieved 2020-12-01. 5. ^ a b Adam, Andy (2014). Grainger & Allison's Diagnostic Radiology (6 ed.). Elsevier Health Sciences. p. 1031. ISBN 9780702061288. Archived from the original on 14 March 2016. 6. ^ Neufeld, Michel; Maclaren, Noel K.; Blizzard, Robert M. (September 1981). "Two Types of Autoimmune Addisonʼs Disease Associated with Different Polyglandular Autoimmune (PGA) Syndromes". Medicine. 60 (5): 355–362. doi:10.1097/00005792-198109000-00003. ISSN 0025-7974. PMID 7024719. S2CID 20641616. 7. ^ Napier, Catherine; Pearce, Simon H.S. (December 2012). "Autoimmune Addison's disease". Presse Médicale. Amsterdam, Netherlands: Elsevier. 41 (12 P 2): e626-35. doi:10.1016/j.lpm.2012.09.010. PMID 23177474. 8. ^ Rajagopalan, Murray Longmore, Ian B. Wilkinson, Supraj R. (2006). Mini Oxford handbook of clinical medicine (6 ed.). Oxford: Oxford University Press. p. 312. ISBN 9780198570714. Archived from the original on 14 March 2016. 9. ^ Rose, Noel R.; Mackay, Ian R. (2014). The autoimmune diseases (5 ed.). San Diego, CA: Elsevier Science. p. 605. ISBN 9780123849304. 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S2CID 33794590. 15. ^ a b Freeman, Hugh James (2016). "Endocrine manifestations in celiac disease". World Journal of Gastroenterology (Review). Pleasanton, California: Baishideng Publishing Group. 22 (38): 8472–8479. doi:10.3748/wjg.v22.i38.8472. PMC 5064028. PMID 27784959. 16. ^ Zhernakova, Alexandra; Withoff, Sebo; Wijmenga, Cisca (2013). "Clinical implications of shared genetics and pathogenesis in autoimmune diseases". Nature Reviews Endocrinology (Review). Berlin, Germany: Springer Nature. 9 (11): 646–59. doi:10.1038/nrendo.2013.161. PMID 23959365. S2CID 28336180. 17. ^ Denham, Jolanda M.; Hill, Ivor D. (2013). "Celiac disease and autoimmunity: review and controversies". Current Allergy Asthma Reports (Review). Berlin, Germany: Springer Science+Business Media. 13 (4): 347–53. doi:10.1007/s11882-013-0352-1. PMC 3725235. PMID 23681421. 18. ^ "Autoimmune polyglandular syndrome type 1 \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Archived from the original on 12 April 2017. Retrieved 26 June 2017. 19. ^ "Autoimmune polyglandular syndrome type 2 \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Archived from the original on 13 April 2017. Retrieved 26 June 2017. 20. ^ Winqvist O, Karlsson FA, Kämpe O (June 1992). "21-Hydroxylase, a major autoantigen in idiopathic Addison's disease". The Lancet. 339 (8809): 1559–62. doi:10.1016/0140-6736(92)91829-W. PMID 1351548. S2CID 19666235. 21. ^ Husebye, Eystein S.; Perheentupa, J; Rautemaa, R; Kämpe, O (May 2009). "Clinical manifestations and management of patients with autoimmune polyendocrine syndrome type I". Journal of Internal Medicine. 265 (5): 514–29. doi:10.1111/j.1365-2796.2009.02090.x. PMID 19382991. S2CID 205339997. 22. ^ Kennedy, Ron. "Addison's Disease". The Doctors' Medical Library. Archived from the original on 12 April 2013. Retrieved 10 April 2013. 23. ^ Laureti S, Casucci G, Santeusanio F, Angeletti G, Aubourg P, Brunetti P (1996). "X-linked adrenoleukodystrophy is a frequent cause of idiopathic Addison's disease in young adult male patient". The Journal of Clinical Endocrinology and Metabolism. 81 (2): 470–474. doi:10.1210/jc.81.2.470. PMID 8636252. 24. ^ Quinkler M, Dahlqvist P, Husebye ES, Kämpe O (Jan 2015). "A European Emergency Card for adrenal insufficiency can save lives". Eur J Intern Med. 26 (1): 75–6. doi:10.1016/j.ejim.2014.11.006. PMID 25498511. 25. ^ a b c Michels A, Michels N (1 April 2014). "Addison disease: early detection and treatment principles". Am Fam Physician. 89 (7): 563–8. PMID 24695602. Archived from the original on 5 September 2015. 26. ^ White, Katherine (28 July 2004). "What to do in an emergency -Addisonian crisis". Addison's Disease Self Help Group. 27. ^ "Eating, Diet, and Nutrition for Adrenal Insufficiency & Addison's Disease \| NIDDK". National Institute of Diabetes and Digestive and Kidney Diseases. Retrieved 2020-12-03. 28. ^ "Adrenal Insufficiency and Addison's Disease". National Endocrine and Metabolic Diseases Information Service. Archived from the original on 26 April 2011. Retrieved 26 November 2010. 29. ^ "Addison's disease - Treatment". NHS Choices. Archived from the original on 9 October 2016. Retrieved 8 October 2016. 30. ^ Bergthorsdottir, Ragnhildur; Leonsson-Zachrisson, Maria; Odén, Anders; Johannsson, Gudmundur (1 December 2006). "Premature Mortality in Patients with Addison's Disease: A Population-Based Study". The Journal of Clinical Endocrinology & Metabolism. 91 (12): 4849–4853. doi:10.1210/jc.2006-0076. ISSN 0021-972X. PMID 16968806. 31. ^ Dimitrios Chantzichristos; Anders Persson; Björn Eliasson; Mervete Miftaraj; Stefan Franzén; Ragnhildur Bergthorsdottir; Soffia Gudbjörnsdottir; Ann-Marie Svensson; Gudmundur Johannsson (1 April 2016). Cushing Syndrome and Primary Adrenal Disorders. Meeting Abstracts. Endocrine Society. pp. OR25–4–OR25–4. doi:10.1210/endo-meetings.2016.ahpaa.9.or25-4 (inactive 2021-01-12).CS1 maint: DOI inactive as of January 2021 (link) 32. ^ Bergthorsdottir, Ragnhildur; Leonsson-Zachrisson, Maria; Odén, Anders; Johannsson, Gudmundur (2006-12-01). "Premature Mortality in Patients with Addison's Disease: A Population-Based Study". The Journal of Clinical Endocrinology & Metabolism. 91 (12): 4849–4853. doi:10.1210/jc.2006-0076. ISSN 0021-972X. PMID 16968806. 33. ^ "Addison Disease". MedicineNet. Archived from the original on 24 June 2007. Retrieved 25 July 2007. 34. ^ a b Odeke, Sylvester. "Addison Disease". eMedicine. Archived from the original on 7 July 2007. Retrieved 25 July 2007. 35. ^ a b "Addison's disease". nhs.uk. 2018-06-22. Retrieved 2020-10-14. 36. ^ Volpé, Robert (1990). Autoimmune Diseases of the Endocrine System. CRC Press. p. 299. ISBN 978-0-8493-6849-3. 37. ^ Addison, Thomas (1855). On The Constitutional And Local Effects Of Disease Of The Supra-Renal Capsules. London: Samuel Highley. Archived from the original on 14 April 2005. 38. ^ Physician and Surgeon. Keating & Bryant. 1885. 39. ^ Patnaik MM, Deshpande AK (May 2008). "Diagnosis–Addison's Disease Secondary to Tuberculosis of the Adrenal Glands". Clinical Medicine & Research. 6 (1): 29. doi:10.3121/cmr.2007.754a. PMC 2442022. PMID 18591375. 40. ^ Bishop PM (1950). "The history of the discovery of Addison's disease". Proceedings of the Royal Society of Medicine. 43 (1): 35–42. doi:10.1177/003591575004300105. PMC 2081266. PMID 15409948. 41. ^ a b Klein, Susan C.; Peterson, Mark E. (January 2010). "Canine hypoadrenocorticism: Part I". The Canadian Veterinary Journal. 51 (1): 63–9. PMC 2797351. PMID 20357943. 42. ^ 1\. Drobatz KJ, Costello MF. Feline Emergency & Critical Care Medicine. Ames, Iowa: Blackwell Publ; 2010. pp. 422–424. 43. ^ Lovelace Tofte, Karen (2018). "Chapter 111. Hypoadrenocorticism". In Norsworthy, Gary D. (ed.). The Feline Patient. John Wiley & Sons. p. 324. ISBN 9781119269038. 44. ^ Stringfield, Cynthia E.; Garne, Michael; Holshuh, H.J. (2000). Addison's disease in a gray seal (Halichoerus grypus). International Association for Aquatic Animal Medicine Proceedings. 45. ^ Sohn, Pam (10 February 2012). "Endangered red panda dies at Chattanooga Zoo". Times Free Press. Retrieved 25 August 2018. 46. ^ Brock, A. Paige; Hall, Natalie H.; Cooke, Kirsten L.; Reese, David J.; Emerson, Jessica A.; Wellehan, James F.X. Jr (June 2013). "Diagnosis and management of atypical hypoadrenocorticism in a variable flying fox (Pteropus hypomelanus)". Journal of Zoo and Wildlife Medicine. 44 (2): 517–9. doi:10.1638/2012-0276R2.1. PMID 23805580. S2CID 38918707. 47. ^ Kline, Sarah; Rooker, Leah; Nobrega-Lee, Michelle; Guthrie, Amanda (March 2015). "Hypoadrenocorticism (Addison's disease) in a Hoffmann's two-toed sloth (Choloepus hoffmanni)". Journal of Zoo and Wildlife Medicine. 46 (1): 171–174. doi:10.1638/2014-0003R2.1. PMID 25831596. S2CID 20775341. 48. ^ a b c d Scott-Moncrieff, J. Catharine (2015). "Chapter 12: Hypoadrenocorticism". In Feldman, Edward C.; Nelson, Richard W.; Reusch, Claudia E.; Scott-Moncrieff, J. Catharine R. (eds.). Canine and Feline Endocrinology (4th ed.). Saunders Elsevier. pp. 485–520. ISBN 978-1-4557-4456-5. 49. ^ Boag, Alisdair; Catchpole, Brian (2014). "A Review of the Genetics of Hypoadrenocorticism". Topics in Companion Animal Medicine. 29 (4): 96–101. doi:10.1053/j.tcam.2015.01.001. PMID 25813849. 50. ^ a b c d Lathan, Patty; Thompson, Ann L. (2018). "Management of hypoadrenocorticism (Addison's disease) in dogs". Veterinary Medicine: Research and Reports. 9: 1–10. doi:10.2147/VMRR.S125617. PMC 6055912. PMID 30050862. ## External links[edit] Wikimedia Commons has media related to Addison's disease. * Addison's disease at Curlie Classification D * ICD-10: E27.1-E27.2 * ICD-9-CM: 255.4 * MeSH: D000224 * DiseasesDB: 222 External resources * MedlinePlus: 000378 * eMedicine: med/42 * Patient UK: Addison's disease * v * t * e Adrenal gland disorder Hyperfunction Aldosterone * Hyperaldosteronism * Primary aldosteronism * Conn syndrome * Bartter syndrome * Glucocorticoid remediable aldosteronism * AME * Liddle's syndrome * 17α CAH * Pseudohypoaldosteronism Cortisol * Cushing's syndrome * Pseudo-Cushing's syndrome * Steroid-induced osteoporosis Sex hormones * 21α CAH * 11β CAH Hypofunction Aldosterone * Hypoaldosteronism * 21α CAH * 11β CAH Cortisol * CAH * Lipoid * 3β * 11β * 17α * 21α Sex hormones * 17α CAH * Inborn errors of steroid metabolism Adrenal insufficiency * Adrenal crisis * Adrenalitis * Xanthogranulomatous * Addison's disease * Waterhouse–Friderichsen syndrome * v * t * e Hypersensitivity and autoimmune diseases Type I/allergy/atopy (IgE) Foreign * Atopic eczema * Allergic urticaria * Allergic rhinitis (Hay fever) * Allergic asthma * Anaphylaxis * Food allergy * common allergies include: Milk * Egg * Peanut * Tree nut * Seafood * Soy * Wheat * Penicillin allergy Autoimmune * Eosinophilic esophagitis Type II/ADCC * * IgM * IgG Foreign * Hemolytic disease of the newborn Autoimmune Cytotoxic * Autoimmune hemolytic anemia * Immune thrombocytopenic purpura * Bullous pemphigoid * Pemphigus vulgaris * Rheumatic fever * Goodpasture syndrome * Guillain–Barré syndrome "Type V"/receptor * Graves' disease * Myasthenia gravis * Pernicious anemia Type III (Immune complex) Foreign * Henoch–Schönlein purpura * Hypersensitivity vasculitis * Reactive arthritis * Farmer's lung * Post-streptococcal glomerulonephritis * Serum sickness * Arthus reaction Autoimmune * Systemic lupus erythematosus * Subacute bacterial endocarditis * Rheumatoid arthritis Type IV/cell-mediated (T cells) Foreign * Allergic contact dermatitis * Mantoux test Autoimmune * Diabetes mellitus type 1 * Hashimoto's thyroiditis * Multiple sclerosis * Coeliac disease * Giant-cell arteritis * Postorgasmic illness syndrome * Reactive arthritis GVHD * Transfusion-associated graft versus host disease Unknown/ multiple Foreign * Hypersensitivity pneumonitis * Allergic bronchopulmonary aspergillosis * Transplant rejection * Latex allergy (I+IV) Autoimmune * Sjögren syndrome * Autoimmune hepatitis * Autoimmune polyendocrine syndrome * APS1 * APS2 * Autoimmune adrenalitis * Systemic autoimmune disease [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Addison's disease	c0001403	25,668	wikipedia	https://en.wikipedia.org/wiki/Addison%27s_disease	2021-01-18T18:41:13	{"gard": ["6722", "5740"], "mesh": ["D000224"], "umls": ["C0405580", "C0001403"], "orphanet": ["101959", "85138"], "wikidata": ["Q8282"]}
Vulvar cancer is the abnormal growth of cells of the vulva, which is part of the female reproductive system and includes the vaginal lips, clitoris, and part of the vagina. Symptoms of vulvar cancer may consist of a lump (mass), itching, or unusual bleeding. Though the exact cause of this cancer is unknown, older women and those who have human papillomavirus have a higher chance of developing vulvar cancer. Treatment may include laser therapy, surgery, chemotherapy, or radiation therapy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Vulvar cancer	c0375071	25,669	gard	https://rarediseases.info.nih.gov/diseases/9349/vulvar-cancer	2021-01-18T17:57:09	{"mesh": ["D014846"], "synonyms": []}
Human disease Enlarged vestibular aqueduct Other namesEnlarged vestibular aqueduct, Dilated vestibular aqueduct or Widened vestibular aqueduct Interior of right osseous labyrinth Large vestibular aqueduct, is a structural deformity of the inner ear. Enlargement of this duct is one of the most common inner ear deformities and is commonly associated with hearing loss during childhood.[1] The term was first discovered in 1791 by Mondini when he was completing a temporal bone dissection. It was then defined by Valvassori and Clemis as a vestibular aqueduct that is greater than or equal to 2.0 mm at the operculum and/or greater than or equal to 1.0 mm at the midpoint. [2]Some use the term enlarged vestibular aqueduct syndrome but this is felt by others to be erroneous as it is a clinical finding which can occur in several syndromes. ## Contents * 1 Symptoms * 2 Pathology * 3 Diagnosis * 4 Management * 5 References * 6 External links ## Symptoms[edit] Although large vestibular aqueducts are a congenital condition, hearing loss may not be present from birth. Age of diagnosis ranges from infancy to adulthood, and symptoms include fluctuating and sometimes progressive sensorineural hearing loss and disequilibrium. It is possible that a small portion of those with large vestibular aqueducts will not exhibit auditory symptoms such as hearing loss. While this is uncommon, hearing loss can progress later in life especially after head trauma.[3] Hearing loss can be unilateral or bilateral and can be sensorineural, conductive, or mixed. Vestibular symptoms, such as vertigo and imbalance, occur in adult patients 45% of the time. [4] ## Pathology[edit] The cochlea and vestibule, viewed from above. (Aquaeductus vestibuli labeled at bottom right The vestibular aqueduct acts as a canal between the inner ear and the cranial cavity. Running through it is a tube called the endolymphatic duct, which normally carries a fluid called endolymph from the inner ear to the endolymphatic sac in the cranial cavity. When the endolymphatic duct and sac are larger than normal, as is the case in large vestibular aqueduct syndrome, endolymph is allowed to travel back from the endolymphatic sac into the inner ear. This often results fluctuations in hearing levels. Enlarged vestibular aqueducts are caused by mutations in gene SLC26A4, which is also associated with Pendred's syndrome and non-syndromic recessive deafness. Enlarged vestibular aqueducts often occur with other inner ear development problems, such as cochlear deformities. Enlarged vestibular aqueducts are part of the classic Mondini deformity. Enlarged vestibular aqueducts with enlarged endolymphatic sacs occur in Pendred syndrome which is caused by a defect on chromosome 7q31.[1] Enlarged vestibular aqueducts can also occur in Branchio-oto-renal syndrome, CHARGE syndrome and renal tubular acidosis. Enlarged vestibular aqueducts can be bilateral or unilateral. Hearing loss caused by large vestibular aqueduct syndrome is not inevitable, although people with the syndrome are at a much higher risk of developing hearing loss than the general population. Hearing loss is very likely. ## Diagnosis[edit] Enlarged vestibular aqueducts are commonly picked up after newborn hearing screen when a child is identified as having a hearing loss. The hearing loss is commonly mixed and can be of any degree when first identified. The conductive component is due to a third window effect caused by the widened vestibular aqueduct. During an audiologic assessment, an air-bone gap in the low frequencies can occur due to the enlarged vestibular aqueduct acting as a third mobile window. Hearing loss in the contralateral ear to the enlarged vestibular aqueduct can also occur due to the chemical composition on both sides.[5] Torticollis has also been found to be an indicator of an enlarged vestibular aqueduct in children. [6] Identification of the enlarged vestibular aqueduct in a child is usually by MRI scan which identifies the fluid within the endolymphatic duct and sac. CT scan may be needed to see the vestibular aqueduct clearly. In adults CT scan may be the first investigation. In order to diagnose the cause of the enlarged vestibular aqueduct the physician will need a detailed family history, full examination to include vestibular examination and, if a bilateral finding, molecular genetic testing as appropriate. With unilateral enlarged vestibular aqueducts molecular genetic testing is currently not recommended. ## Management[edit] There is no treatment to correct an enlarged vestibular aqueduct. Any hearing loss will need management with amplification and support in education and at work. If the hearing loss becomes severe to profound, cochlear implants can be of significant value. Vestibular disturbance is usually short-lived and associated with head trauma but significant vestibular hypofunction may require rehabilitation. People with enlarged vestibular aqueducts are advised to avoid head trauma where possible. This usually means avoiding contact sports such as football, boxing, rugby, horse riding, trampolining and other sports where head injury may occur. Some have symptoms when flying and should limit these activities if affected. ## References[edit] 1. ^ a b S. Usami; Satoko Abe; Mike D. Weston; Hideichi Shinkawa; Guy Van Camp; William J. Kimberling (1999), "Non-syndromic hearing loss associated with enlarged vestibular aqueduct is caused by PDS mutations", Human Genetics, 104 (2): 188–192, doi:10.1007/s004390050933, PMID 10190331, S2CID 3116063 2. ^ Yang, Christina (2016). "Vestibular Pathology in Children with enlarged vestibular aqueduct". The Laryngoscope. 126 (10): 2344–50. doi:10.1002/lary.25890. PMID 26864825. 3. ^ Madden, Colm; Halsted, Mark; Benton, Corning; Greinwald, John; Choo, Daniel (July 2003), "Enlarged Vestibular Aqueduct Syndrome in the Pediatric Population", Otology & Neurotology, 24 (4): 625–632, doi:10.1097/00129492-200307000-00016, PMID 12851556, S2CID 44980735 4. ^ Grimmer, J (2007). "Vestibular symptoms in children with enlarged vestibular aqueduct anomaly". International Journal of Pediatric Otorhinolaryngology. 71 (2): 275–82. doi:10.1016/j.ijporl.2006.10.010. PMID 17113162. 5. ^ Greinwald, J (2013). "Significance of unilateral enlarged vestibular aqueduct". The Laryngoscope. 123 (6): 1537–46. doi:10.1002/lary.23889. PMID 23401162. 6. ^ Brodsky, J (2020). "Torticollis in children with enlarged vestibular aqueducts". International Journal of Pediatric Otorhinolaryngology. 131: 109862. doi:10.1016/j.ijporl.2020.109862. PMID 31927148. ## External links[edit] Classification D * OMIM: 600791 * MeSH: C566366 * v * t * e Genetic disorders relating to deficiencies of transcription factor or coregulators (1) Basic domains 1.2 * Feingold syndrome * Saethre–Chotzen syndrome 1.3 * Tietz syndrome (2) Zinc finger DNA-binding domains 2.1 * (Intracellular receptor): Thyroid hormone resistance * Androgen insensitivity syndrome * PAIS * MAIS * CAIS * Kennedy's disease * PHA1AD pseudohypoaldosteronism * Estrogen insensitivity syndrome * X-linked adrenal hypoplasia congenita * MODY 1 * Familial partial lipodystrophy 3 * SF1 XY gonadal dysgenesis 2.2 * Barakat syndrome * Tricho–rhino–phalangeal syndrome 2.3 * Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome * Denys–Drash syndrome * Duane-radial ray syndrome * MODY 7 * MRX 89 * Townes–Brocks syndrome * Acrocallosal syndrome * Myotonic dystrophy 2 2.5 * Autoimmune polyendocrine syndrome type 1 (3) Helix-turn-helix domains 3.1 * ARX * Ohtahara syndrome * Lissencephaly X2 * MNX1 * Currarino syndrome * HOXD13 * SPD1 synpolydactyly * PDX1 * MODY 4 * LMX1B * Nail–patella syndrome * MSX1 * Tooth and nail syndrome * OFC5 * PITX2 * Axenfeld syndrome 1 * POU4F3 * DFNA15 * POU3F4 * DFNX2 * ZEB1 * Posterior polymorphous corneal dystrophy * Fuchs' dystrophy 3 * ZEB2 * Mowat–Wilson syndrome 3.2 * PAX2 * Papillorenal syndrome * PAX3 * Waardenburg syndrome 1&3 * PAX4 * MODY 9 * PAX6 * Gillespie syndrome * Coloboma of optic nerve * PAX8 * Congenital hypothyroidism 2 * PAX9 * STHAG3 3.3 * FOXC1 * Axenfeld syndrome 3 * Iridogoniodysgenesis, dominant type * FOXC2 * Lymphedema–distichiasis syndrome * FOXE1 * Bamforth–Lazarus syndrome * FOXE3 * Anterior segment mesenchymal dysgenesis * FOXF1 * ACD/MPV * FOXI1 * Enlarged vestibular aqueduct * FOXL2 * Premature ovarian failure 3 * FOXP3 * IPEX 3.5 * IRF6 * Van der Woude syndrome * Popliteal pterygium syndrome (4) β-Scaffold factors with minor groove contacts 4.2 * Hyperimmunoglobulin E syndrome 4.3 * Holt–Oram syndrome * Li–Fraumeni syndrome * Ulnar–mammary syndrome 4.7 * Campomelic dysplasia * MODY 3 * MODY 5 * SF1 * SRY XY gonadal dysgenesis * Premature ovarian failure 7 * SOX10 * Waardenburg syndrome 4c * Yemenite deaf-blind hypopigmentation syndrome 4.11 * Cleidocranial dysostosis (0) Other transcription factors 0.6 * Kabuki syndrome Ungrouped * TCF4 * Pitt–Hopkins syndrome * ZFP57 * TNDM1 * TP63 * Rapp–Hodgkin syndrome/Hay–Wells syndrome/Ectrodactyly–ectodermal dysplasia–cleft syndrome 3/Limb–mammary syndrome/OFC8 Transcription coregulators Coactivator: * CREBBP * Rubinstein–Taybi syndrome Corepressor: * HR (Atrichia with papular lesions) [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Enlarged vestibular aqueduct	c1863752	25,670	wikipedia	https://en.wikipedia.org/wiki/Enlarged_vestibular_aqueduct	2021-01-18T18:56:36	{"gard": ["8651"], "mesh": ["C566366"], "umls": ["C1863752"], "wikidata": ["Q2241556"]}
## Description Prosopagnosia is the inability to recognize someone by the face alone, in the absence of sensory or intellectual impairment (Schwarzer et al., 2007). Almost all reported cases are of the acquired form, but there is evidence for a familial form as well (McConachie, 1976; de Haan, 1999; Galaburda and Duchaine, 2003; Kennerknecht et al., 2006). Clinical Features McConachie (1976) described a 12-year-old girl who had never been able to recognize any but the most familiar faces. Examination and testing revealed some evidence of right hemisphere abnormality on EEG, some directional confusion and disturbance of topographic memory, and difficulty with complex visual discrimination and integration. Her mother also reported difficulty with recognizing familiar faces, raising the possibility of familial transmission. McConachie (1976) noted that because so-called 'developmental prosopagnosia,' in which there is no history of brain injury, can be circumvented by various strategies, it might be more common than is generally believed. De Haan and Campbell (1991) reexamined the patient originally described by McConachie (1976) and administered an extensive series of tests of face recognition ability and related functions, comparing her performance to that of 4 women of comparable educational background and age. The patient's basic visuosensory functions, such as acuity, contrast sensitivity, and color perception, were largely intact; and general face perception, e.g., distinguishing between a face and a 'nonface,' was relatively well preserved. Recognition of familiar faces was severely impaired, and she also showed problems with other face-processing tasks, such as analysis of facial expression, and with object recognition. This apparent functional impairment was supported by subsequent studies, which demonstrated a complete absence of covert face recognition. De Haan (1999) studied a family in which several members had difficulty with face recognition to such a degree that the mother would instruct them beforehand about who was coming to visit, and the father once introduced himself to his own daughter when they met in an unusual setting. Upon examination, the father and 2 daughters tested very poorly on a familiar face recognition task, whereas the mother and a brother had no face recognition deficit. Another sister, who reportedly had no difficulty with face recognition, declined to participate in the study. Galaburda and Duchaine (2003) reported a 4-generation family with prosopagnosia, including father-to-son transmission. The proband was a 42-year-old man who recalled incidents early in childhood when he could not recognize close family members, and he had failed to recognize nearly all his relatives at times. It was not until he entered the army that he realized the severity of his problem, when the uniform appearance of his fellow servicemen left him unable to differentiate between people. He also reported that he frequently mistook strangers for acquaintances. His son, mother, and grandmother also had prosopagnosia. Schwarzer et al. (2007), commenting on their clinical experience with 38 hereditary prosopagnosics, stated that all of the patients reported that throughout their entire life they had been unable to recognize people by their faces alone, sometimes not even recognizing very close relatives, and used context and other attributes such as voice and hair to identify individuals. Schwarzer et al. (2007) noted that the perception of facial details is not grossly distorted in these patients, all of whom can perceive normal attractiveness and emotions and can identify gender. In a detailed study of the gaze behavior of 8 hereditary prosopagnosics compared to 4 gender- and age-matched controls, Schwarzer et al. (2007) found that while the control participants focused their gaze on the central facial features in face recognition tasks, the hereditary prosopagnosics had a more dispersed gaze and also fixated on external facial features. The difference in gaze pattern was independent of recognition performance, i.e., even when the prosopagnosics recognized a face correctly, compared to the control participants their gaze was significantly more dispersed. Schwarzer et al. (2007) concluded that the face recognition impairment of hereditary prosopagnosics is reflected in their gaze behavior. Kennerknecht et al. (2007) reported an Indian woman with hereditary prosopagnosia. She described identifying people by hair cuts, glasses, teeth, clothing, and sometimes by smile. She had normal recognition of attractiveness but had difficulty with inner imaging of her parents, close friends, and some objects. Neurologic exam showed no other abnormalities. She was socially well-integrated and was a university student of high caliber. Family history revealed a total of 8 other affected members from both the maternal and paternal sides of the family. Her mother, but not her father, was affected. Kennerknecht et al. (2007) suggested that the occurrence in both sides of the family was consistent with a high prevalence of the disorder. Kennerknecht et al. (2008) reported detailed clinical features of 10 unrelated Chinese medical students with prosopagnosia. All prosopagnosic students had pronounced difficulties in the recognition of close relatives and had often been reproached for not greeting them. All reported the use of compensatory strategies and behavioral adaptation, such as reliance on multiple extrafacial cues including gesture, spectacles, gait, hairstyle, perfume, clothing, and jewelry, or arriving early at social meetings to avoid having to locate people. They also had difficulties in recognizing key actors or actresses in movies or television and had to rely on their friends to navigate them through the stories. Inheritance Kennerknecht et al. (2006) reported a German family with prosopagnosia occurring over 3 generations in both sexes and in half sibs, with 2 instances of father-to-son transmission, consistent with autosomal dominant inheritance. Population Genetics From a survey conducted in 3 local high schools and 1 university in Germany, Kennerknecht et al. (2006) analyzed 689 completed questionnaires and identified 65 individuals who were 'highly suspicious' for congenital prosopagnosia. After in-depth interviews of 43 individuals, the diagnosis was established in 17 persons (6 males and 11 females), yielding a prevalence of 2.47% in the German Caucasian population. Of those 17 cases, 14 allowed interviewing of at least 1 first-degree relative, and all had at least 1 affected first-degree relative. Kennerknecht et al. (2006) concluded that congenital prosopagnosia is a very common cognitive disorder that is almost always familial, and suggested that the long-term use of compensatory strategies prevents many affected individuals from realizing that they have a specific dysfunction. Using a questionnaire-based screening method, Kennerknecht et al. (2007) identified 1 female Bengali student with prosopagnosia among a total of 189 native Indian university students. Using a questionnaire of 533 Chinese Han medical students followed by personal interviews in a selected subgroup, Kennerknecht et al. (2008) identified 10 (1.88%) individuals with prosopagnosia, including 4 with a family history of prosopagnosia consistent with autosomal dominant inheritance. In an accompanying commentary, Duchaine (2008) suggested that there may be a difference between heritable forms of the disorder and nonheritable forms. He reported that only 11 (58%) of 19 prosopagnosic individuals in his own study clearly had affected relatives. Duchaine (2008) further suggested that the 6 affected individuals reported by Kennerknecht et al. (2008) who did not have a family history of the disorder may not have had a heritable form, thus reducing the frequency to 0.75%. However, even this reduced frequency would still represent a 'staggering number of Han Chinese with hereditary face recognition problems,' about 9.75 million. History The term prosopagnosia was coined by Bodamer (1947), from the Greek 'prosopon,' meaning 'face,' and 'agnosia,' meaning 'ignorance.' Joachim Bodamer was a German neurologist who described 3 soldiers with acquired prosopagnosia due to head wounds sustained during World War II. INHERITANCE \- Autosomal dominant NEUROLOGIC Behavioral Psychiatric Manifestations \- Inability to recognize someone familiar by the face alone ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	PROSOPAGNOSIA, HEREDITARY	c2931455	25,671	omim	https://www.omim.org/entry/610382	2019-09-22T16:04:42	{"mesh": ["C537242"], "omim": ["610382"], "synonyms": ["Alternative titles", "FACE BLINDNESS", "PROSOPAGNOSIA, DEVELOPMENTAL", "PROSOPAGNOSIA, CONGENITAL"]}
A number sign (#) is used with this entry because this form of methemoglobinemia is caused by heterozygous mutation in the beta-globin gene (HBB; 141900) that produces M hemoglobin, a methemoglobin not amenable to reduction, or a hemoglobin with an unusual susceptibility to oxidizing agents. Description Methemoglobinemia is a clinical condition in which more than 1% of hemoglobin is oxidized to methemoglobin, a type of hemoglobin that contains the ferric (Fe3+) form of iron. Patients with hemoglobin M are cyanotic but otherwise asymptomatic. If the mutation occurs in the hemoglobin alpha subunit (141800), cyanosis is apparent at birth, whereas if the beta chain is affected, cyanosis appears later or intensifies when beta subunit production increases. If a newborn carries a fetal M hemoglobin (gamma subunit; 142250), cyanosis disappears when the complete gamma-beta-switch occurs (summary by Mansouri and Lurie, 1993). Clinical Features Gerald and Efron (1961) reviewed 5 different M hemoglobins, all of which caused chronic cyanosis due to the occurrence of methemoglobinemia. Inheritance Methemoglobinemia caused by mutation in the beta-globin gene is inherited in an autosomal dominant manner. Molecular Genetics Hayashi et al. (1969) noted that 4 M hemoglobins, Hb M (Iwate) (141800.0093), Hb M (Hyde Park) (141900.0164), Hb M (Boston) (114800.0092), and Hb M (Saskatoon) (141900.0165), have a structural abnormality in the proximal or the distal histidine of the alpha or beta subunits of the Hb molecule and have the same kind of amino acid substitution, histidine to tyrosine. These 4 amino acids are critical to the binding of the heme group. A fifth variant of Hb M, Hb M (Milwaukee-1) (141900.0165), has a valine to glutamic acid substitution at a position 4 residues or one helical turn from the distal histidine. Mansouri and Lurie (1993) noted that in this Hb variant, the carboxylic group of the glutamic acid forms a bond with iron, thus stabilizing it in the oxidized form. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	METHEMOGLOBINEMIA, BETA TYPE	c4693797	25,672	omim	https://www.omim.org/entry/617971	2019-09-22T15:44:12	{"omim": ["617971"], "orphanet": ["330041"], "synonyms": ["M hemoglobinopathy"]}
Deadly viral disease This article is about rabies in humans. For rabies in animals, see Rabies in animals. For other uses, see Rabies (disambiguation). "Rabid" redirects here. For other uses, see Rabid (disambiguation). Rabies A man with rabies, 1958 SpecialtyInfectious disease SymptomsFever, fear of water, confusion, excessive salivation, hallucinations, trouble sleeping, paralysis, coma[1][2] CausesRabies virus, Australian bat lyssavirus[3] PreventionRabies vaccine, animal control, rabies immunoglobulin[1] TreatmentSupportive care PrognosisNearly always death after onset of symptoms[1] Deaths17,400 (2015)[4] Rabies is a viral disease that causes inflammation of the brain in humans and other mammals.[1] Early symptoms can include fever and tingling at the site of exposure.[1] These symptoms are followed by one or more of the following symptoms: violent movements, uncontrolled excitement, fear of water, an inability to move parts of the body, confusion, and loss of consciousness.[1] Once symptoms appear, the result is nearly always death.[1] The time period between contracting the disease and the start of symptoms is usually one to three months, but can vary from less than one week to more than one year.[1] The time depends on the distance the virus must travel along peripheral nerves to reach the central nervous system.[5] Rabies is caused by lyssaviruses, including the rabies virus and Australian bat lyssavirus.[3] It is spread when an infected animal bites or scratches a human or other animal.[1] Saliva from an infected animal can also transmit rabies if the saliva comes into contact with the eyes, mouth, or nose.[1] Globally, dogs are the most common animal involved.[1] In countries where dogs commonly have the disease, more than 99% of rabies cases are the direct result of dog bites.[6] In the Americas, bat bites are the most common source of rabies infections in humans, and less than 5% of cases are from dogs.[1][6] Rodents are very rarely infected with rabies.[6] The disease can be diagnosed only after the start of symptoms.[1] Animal control and vaccination programs have decreased the risk of rabies from dogs in a number of regions of the world.[1] Immunizing people before they are exposed is recommended for those at high risk, including those who work with bats or who spend prolonged periods in areas of the world where rabies is common.[1] In people who have been exposed to rabies, the rabies vaccine and sometimes rabies immunoglobulin are effective in preventing the disease if the person receives the treatment before the start of rabies symptoms.[1] Washing bites and scratches for 15 minutes with soap and water, povidone-iodine, or detergent may reduce the number of viral particles and may be somewhat effective at preventing transmission.[1][7] As of 2016[update], only fourteen people had survived a rabies infection after showing symptoms.[8][9][10] Rabies caused about 17,400 human deaths worldwide in 2015.[4] More than 95% of human deaths from rabies occur in Africa and Asia.[1] About 40% of deaths occur in children under the age of 15.[11] Rabies is present in more than 150 countries and on all continents but Antarctica.[1] More than 3 billion people live in regions of the world where rabies occurs.[1] A number of countries, including Australia and Japan, as well as much of Western Europe, do not have rabies among dogs.[12][13] Many Pacific islands do not have rabies at all.[13] It is classified as a neglected tropical disease.[14] ## Contents * 1 Signs and symptoms * 2 Cause * 3 Transmission * 4 Diagnosis * 5 Prevention * 6 Treatment * 6.1 After exposure * 6.2 After onset * 7 Prognosis * 8 Epidemiology * 8.1 India * 8.2 Australia * 8.3 United States * 8.4 Europe * 8.5 Mexico * 9 History * 9.1 Etymology * 10 Other animals * 11 Research * 12 See also * 13 References * 14 External links ## Signs and symptoms Play media A typical rabies patient displaying hydrophobia Animals with "dumb" rabies appear depressed, lethargic, and uncoordinated The period between infection and the first symptoms (incubation period) is typically 1–3 months in humans.[15] This period may be as short as four days or longer than six years, depending on the location and severity of the wound and the amount of virus introduced.[15] Initial symptoms of rabies are often nonspecific such as fever and headache.[15] As rabies progresses and causes inflammation of the brain and meninges, symptoms can include slight or partial paralysis, anxiety, insomnia, confusion, agitation, abnormal behavior, paranoia, terror, and hallucinations.[5][15] The person may also have fear of water.[1] The symptoms eventually progress to delirium, and coma.[5][15] Death usually occurs 2 to 10 days after first symptoms. Survival is almost unknown once symptoms have presented, even with intensive care.[15][16] Rabies has also occasionally been referred to as hydrophobia ("fear of water") throughout its history.[17] It refers to a set of symptoms in the later stages of an infection in which the person has difficulty swallowing, shows panic when presented with liquids to drink, and cannot quench their thirst. Any mammal infected with the virus may demonstrate hydrophobia.[18] Saliva production is greatly increased, and attempts to drink, or even the intention or suggestion of drinking, may cause excruciatingly painful spasms of the muscles in the throat and larynx. Since the infected individual cannot swallow saliva and water, the virus has a much higher chance of being transmitted, since it multiplies and accumulates in the salivary glands and is transmitted through biting.[19] Hydrophobia is commonly associated with furious rabies, which affects 80% of rabies-infected people. The remaining 20% may experience a paralytic form of rabies that is marked by muscle weakness, loss of sensation, and paralysis; this form of rabies does not usually cause fear of water.[18] ## Cause Rendering of the rabies virus TEM micrograph with numerous rabies virions (small, dark grey, rodlike particles) and Negri bodies (the larger pathognomonic cellular inclusions of rabies infection) Rabies is caused by a number of lyssaviruses including the rabies virus and Australian bat lyssavirus.[3] Duvenhage lyssavirus may cause a rabies-like infection.[20] The rabies virus is the type species of the Lyssavirus genus, in the family Rhabdoviridae, order Mononegavirales. Lyssavirions have helical symmetry, with a length of about 180 nm and a cross-section of about 75 nm.[21] These virions are enveloped and have a single-stranded RNA genome with negative sense. The genetic information is packed as a ribonucleoprotein complex in which RNA is tightly bound by the viral nucleoprotein. The RNA genome of the virus encodes five genes whose order is highly conserved: nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G), and the viral RNA polymerase (L).[22] To enter cells, trimeric spikes on the exterior of the membrane of the virus interact with a specific cell receptor, the most likely one being the acetylcholine receptor. The cellular membrane pinches in a procession known as pinocytosis and allows entry of the virus into the cell by way of an endosome. The virus then uses the acidic environment, which is necessary, of that endosome and binds to its membrane simultaneously, releasing its five proteins and single strand RNA into the cytoplasm.[23] Once within a muscle or nerve cell, the virus undergoes replication. The L protein then transcribes five mRNA strands and a positive strand of RNA all from the original negative strand RNA using free nucleotides in the cytoplasm. These five mRNA strands are then translated into their corresponding proteins (P, L, N, G and M proteins) at free ribosomes in the cytoplasm. Some proteins require post-translative modifications. For example, the G protein travels through the rough endoplasmic reticulum, where it undergoes further folding, and is then transported to the Golgi apparatus, where a sugar group is added to it (glycosylation).[23] When there are enough viral proteins, the viral polymerase will begin to synthesize new negative strands of RNA from the template of the positive strand RNA. These negative strands will then form complexes with the N, P, L and M proteins and then travel to the inner membrane of the cell, where a G protein has embedded itself in the membrane. The G protein then coils around the N-P-L-M complex of proteins taking some of the host cell membrane with it, which will form the new outer envelope of the virus particle. The virus then buds from the cell.[23] From the point of entry, the virus is neurotropic, traveling along the neural pathways into the central nervous system. The virus usually first infects muscle cells close to the site of infection, where they are able to replicate without being 'noticed' by the host's immune system. Once enough virus has been replicated, they begin to bind to acetylcholine receptors at the neuromuscular junction.[24] The virus then travels through the nerve cell axon via retrograde transport, as its P protein interacts with dynein, a protein present in the cytoplasm of nerve cells. Once the virus reaches the cell body it travels rapidly to the central nervous system (CNS), replicating in motor neurons and eventually reaching the brain.[5] After the brain is infected, the virus travels centrifugally to the peripheral and autonomic nervous systems, eventually migrating to the salivary glands, where it is ready to be transmitted to the next host.[25]:317 Two dogs with the paralytic, or dumb, form of rabies. ## Transmission Main article: Rabies transmission All warm-blooded species, including humans, may become infected with the rabies virus and develop symptoms. Birds were first artificially infected with rabies in 1884; however, infected birds are largely, if not wholly, asymptomatic, and recover.[26] Other bird species have been known to develop rabies antibodies, a sign of infection, after feeding on rabies-infected mammals.[27][28] The virus has also adapted to grow in cells of cold-blooded vertebrates.[29][30] Most animals can be infected by the virus and can transmit the disease to humans. Infected bats,[31][32] monkeys, raccoons, foxes, skunks, cattle, wolves, coyotes, dogs, cats, and mongooses (normally either the small Asian mongoose or the yellow mongoose)[33] present the greatest risk to humans. Rabies may also spread through exposure to infected bears, domestic farm animals, groundhogs, weasels, and other wild carnivorans. However, lagomorphs, such as hares and rabbits, and small rodents such as chipmunks, gerbils, guinea pigs, hamsters, mice, rats, and squirrels, are almost never found to be infected with rabies and are not known to transmit rabies to humans.[34] Bites from mice, rats, or squirrels rarely require rabies prevention because these rodents are typically killed by any encounter with a larger, rabid animal, and would, therefore, not be carriers.[35] The Virginia opossum has a lower internal body temperature than the rabies virus prefers and therefore is resistant but not immune to rabies.[36] The virus is usually present in the nerves and saliva of a symptomatic rabid animal.[37][38] The route of infection is usually, but not always, by a bite. In many cases, the infected animal is exceptionally aggressive, may attack without provocation, and exhibits otherwise uncharacteristic behavior.[39] This is an example of a viral pathogen modifying the behavior of its host to facilitate its transmission to other hosts. After a typical human infection by bite, the virus enters the peripheral nervous system. It then travels along the afferent nerves toward the central nervous system.[40] During this phase, the virus cannot be easily detected within the host, and vaccination may still confer cell-mediated immunity to prevent symptomatic rabies. When the virus reaches the brain, it rapidly causes encephalitis, the prodromal phase, which is the beginning of the symptoms. Once the patient becomes symptomatic, treatment is almost never effective and mortality is over 99%. Rabies may also inflame the spinal cord, producing transverse myelitis.[41][42] Although it is theoretically possible for rabies-infected humans to transmit it to others by biting or otherwise, no such cases have ever been documented, since infected humans are usually hospitalized and necessary precautions taken. Casual contact, such as touching a person with rabies or contact with non-infectious fluid or tissue (urine, blood, feces) does not constitute an exposure and does not require post-exposure prophylaxis. But as the virus is present in sperm and vaginal secretions, it might be possible for rabies to spread through sex.[43] There are only a handful of recorded cases of human-to-human transmission of rabies, and all occurred through organ transplants from infected donors.[44][45] ## Diagnosis Rabies can be difficult to diagnose because, in the early stages, it is easily confused with other diseases or with aggressiveness.[46] The reference method for diagnosing rabies is the fluorescent antibody test (FAT), an immunohistochemistry procedure, which is recommended by the World Health Organization (WHO).[47] The FAT relies on the ability of a detector molecule (usually fluorescein isothiocyanate) coupled with a rabies-specific antibody, forming a conjugate, to bind to and allow the visualisation of rabies antigen using fluorescent microscopy techniques. Microscopic analysis of samples is the only direct method that allows for the identification of rabies virus-specific antigen in a short time and at a reduced cost, irrespective of geographical origin and status of the host. It has to be regarded as the first step in diagnostic procedures for all laboratories. Autolysed samples can, however, reduce the sensitivity and specificity of the FAT.[48] The RT PCR assays proved to be a sensitive and specific tool for routine diagnostic purposes,[49] particularly in decomposed samples[50] or archival specimens.[51] The diagnosis can be reliably made from brain samples taken after death. The diagnosis can also be made from saliva, urine, and cerebrospinal fluid samples, but this is not as sensitive or reliable as brain samples.[48] Cerebral inclusion bodies called Negri bodies are 100% diagnostic for rabies infection but are found in only about 80% of cases.[21] If possible, the animal from which the bite was received should also be examined for rabies.[52] Some light microscopy techniques may also be used to diagnose rabies at a tenth of the cost of traditional fluorescence microscopy techniques, allowing identification of the disease in less-developed countries.[53] A test for rabies, known as LN34, is easier to run on a dead animal's brain and might help determine who does and does not need post-exposure prevention.[54] The test was developed by the CDC in 2018.[54] The differential diagnosis in a case of suspected human rabies may initially include any cause of encephalitis, in particular infection with viruses such as herpesviruses, enteroviruses, and arboviruses such as West Nile virus. The most important viruses to rule out are herpes simplex virus type one, varicella zoster virus, and (less commonly) enteroviruses, including coxsackieviruses, echoviruses, polioviruses, and human enteroviruses 68 to 71.[55] New causes of viral encephalitis are also possible, as was evidenced by the 1999 outbreak in Malaysia of 300 cases of encephalitis with a mortality rate of 40% caused by Nipah virus, a newly recognized paramyxovirus.[56] Likewise, well-known viruses may be introduced into new locales, as is illustrated by the outbreak of encephalitis due to West Nile virus in the eastern United States.[57] Epidemiologic factors, such as season, geographic location, and the patient's age, travel history, and possible exposure to bites, rodents, and ticks, may help direct the diagnosis. ## Prevention Further information: Dog bite prevention Almost all human exposure to rabies was fatal until a vaccine was developed in 1885 by Louis Pasteur and Émile Roux. Their original vaccine was harvested from infected rabbits, from which the virus in the nerve tissue was weakened by allowing it to dry for five to ten days.[58] Similar nerve tissue-derived vaccines are still used in some countries, as they are much cheaper than modern cell culture vaccines.[59] The human diploid cell rabies vaccine was started in 1967. Less expensive purified chicken embryo cell vaccine and purified vero cell rabies vaccine are now available.[52] A recombinant vaccine called V-RG has been used in Belgium, France, Germany, and the United States to prevent outbreaks of rabies in undomesticated animals.[60] Immunization before exposure has been used in both human and nonhuman populations, where, as in many jurisdictions, domesticated animals are required to be vaccinated.[61] A female child about to receive PEP after being bitten by an animal thought to be rabid. The Missouri Department of Health and Senior Services Communicable Disease Surveillance 2007 Annual Report states the following can help reduce the risk of contracting rabies:[62] * Vaccinating dogs, cats, and ferrets against rabies * Keeping pets under supervision * Not handling wild animals or strays * Contacting an animal control officer upon observing a wild animal or a stray, especially if the animal is acting strangely * If bitten by an animal, washing the wound with soap and water for 10 to 15 minutes and contacting a healthcare provider to determine if post-exposure prophylaxis is required 28 September is World Rabies Day, which promotes the information, prevention, and elimination of the disease.[63] In Asia and in parts of the Americas and Africa, dogs remain the principal host. Mandatory vaccination of animals is less effective in rural areas. Especially in developing countries, pets may not be privately kept and their destruction may be unacceptable. Oral vaccines can be safely distributed in baits, a practice that has successfully reduced rabies in rural areas of Canada, France, and the United States. In Montreal, Quebec, Canada, baits are successfully used on raccoons in the Mount-Royal Park area. Vaccination campaigns may be expensive, and cost-benefit analysis suggests baits may be a cost-effective method of control.[64] In Ontario, a dramatic drop in rabies was recorded when an aerial bait-vaccination campaign was launched.[65] The number of recorded human deaths from rabies in the United States has dropped from 100 or more annually in the early 20th century to one or two per year due to widespread vaccination of domestic dogs and cats and the development of human vaccines and immunoglobulin treatments. Most deaths now result from bat bites, which may go unnoticed by the victim and hence untreated.[66] ## Treatment ### After exposure Treatment after exposure can prevent the disease if given within 10 days. The rabies vaccine is 100% effective if given early, and still has a chance of success if delivery is delayed.[21][23][67] Every year, more than 15 million people get vaccination after potential exposure. While this works well, the cost is significant.[68] In the US it is recommended people receive one dose of human rabies immunoglobulin (HRIG) and four doses of rabies vaccine over a 14-day period.[69] HRIG is expensive and makes up most of the cost of post exposure treatment, ranging as high as several thousand dollars.[70] As much as possible of this dose should be injected around the bites, with the remainder being given by deep intramuscular injection at a site distant from the vaccination site.[23] People who have previously been vaccinated against rabies do not need to receive the immunoglobulin, only the postexposure vaccinations on days 0 and 3.[71] The side effects of modern cell-based vaccines are similar to the side effects of flu shots. The old nerve-tissue-based vaccination required multiple injections into the abdomen with a large needle but is inexpensive.[52] It is being phased out and replaced by affordable World Health Organization intradermal-vaccination regimens.[52] Intramuscular vaccination should be given into the deltoid, not the gluteal area, which has been associated with vaccination failure[citation needed] due to injection into fat rather than muscle. In children less than a year old, the lateral thigh is recommended.[72] Thoroughly washing the wound as soon as possible with soap and water for approximately five minutes is effective in reducing the number of viral particles.[73] Povidone-iodine or alcohol is then recommended to reduce the virus further.[74] Awakening to find a bat in the room, or finding a bat in the room of a previously unattended child or mentally disabled or intoxicated person, is an indication for post-exposure prophylaxis (PEP). The recommendation for the precautionary use of PEP in bat encounters where no contact is recognized has been questioned in the medical literature, based on a cost–benefit analysis.[75] However, a 2002 study has supported the protocol of precautionary administering of PEP where a child or mentally compromised individual has been alone with a bat, especially in sleep areas, where a bite or exposure may occur with the victim being unaware.[76] ### After onset A treatment known as the Milwaukee protocol, which involves putting a person into a chemically induced coma and using antiviral medications, has been proposed but subsequently found not to be useful.[77] It initially came into use in 2003, following Jeanna Giese, a teenager from Wisconsin, becoming the first person known to have survived rabies without preventive treatments before symptom onset.[78][79] She, however, already had antibodies against rabies when she initially arrived in hospital.[80] While this treatment has been tried multiple times more, there have been no further cases of survival.[77] The protocol has since been assessed as an ineffective treatment with concerns related to the costs and ethics of its use.[77][81] ## Prognosis Vaccination after exposure, PEP, is highly successful in preventing the disease.[67] In unvaccinated humans, rabies is almost always fatal after neurological symptoms have developed.[82] ## Epidemiology Main article: Prevalence of rabies Deaths from rabies per million persons in 2012 0 1 2–4 5–9 10–17 18–69 Map of rabies-free countries and territories In 2010, an estimated 26,000 people died from rabies, down from 54,000 in 1990.[83] The majority of the deaths occurred in Asia and Africa.[82] As of 2015[update], India, followed by China (approximately 6,000), and the Democratic Republic of the Congo (5,600) had the most cases.[84] A 2015 collaboration between the World Health Organization, World Organization of Animal Health (OIE), Food and Agriculture Organization of the United Nation (FAO), and Global Alliance for Rabies Control has a goal of eliminating deaths from rabies by 2030.[85] ### India India has the highest rate of human rabies in the world, primarily because of stray dogs,[86] whose number has greatly increased since a 2001 law forbade the killing of dogs.[87] Effective control and treatment of rabies in India is hindered by a form of mass hysteria known as puppy pregnancy syndrome (PPS). Dog bite victims with PPS, male as well as female, become convinced that puppies are growing inside them, and often seek help from faith healers rather than medical services.[88] An estimated 20,000 people die every year from rabies in India, more than a third of the global total.[87] ### Australia The rabies virus survives in widespread, varied, rural animal reservoirs. Despite Australia's official rabies-free status,[89] Australian bat lyssavirus (ABLV), discovered in 1996, is a strain of rabies prevalent in native bat populations. There have been three human cases of ABLV in Australia, all of them fatal. ### United States Rabies cases in humans and domestic animals — United States, 1938–2018 Canine-specific rabies has been eradicated in the United States. But rabies is common among wild animals in the United States, and an average of 100 dogs become infected from other wildlife each year.[90][91] Bats, raccoons, skunks and foxes account for almost all reported cases (98% in 2009). Rabid bats are found in all 48 contiguous states. Other reservoirs are more limited geographically; for example, the raccoon rabies virus variant is only found in a relatively narrow band along the East Coast. Due to a high public awareness of the virus, efforts at vaccination of domestic animals and curtailment of feral populations, and availability of postexposure prophylaxis, incidence of rabies in humans is very rare in the United States. From 1960 to 2018, a total of 125 human rabies cases were reported in the United States; 36 (28%) were attributed to dog bites during international travel.[92] Among the 89 infections acquired in the United States, 62 (70%) were attributed to bats.[92] No Americans have died from rabies since 2018, when a 55-year-old Utah man who had "extensive contact with bats" died from the disease.[93] ### Europe Either no or very few cases of rabies are reported each year in Europe; cases are contracted both during travel and in Europe.[94] In Switzerland the disease was virtually eliminated after scientists placed chicken heads laced with live attenuated vaccine in the Swiss Alps.[65] The foxes of Switzerland, proven to be the main source of rabies in the country, ate the chicken heads and immunized themselves.[65][95] Italy, after being declared rabies-free from 1997 to 2008, has witnessed a reemergence of the disease in wild animals in the Triveneto regions (Trentino-Alto Adige/Südtirol, Veneto and Friuli-Venezia Giulia), due to the spreading of an epidemic in the Balkans that also affected Austria. An extensive wild animal vaccination campaign eliminated the virus from Italy again, and it regained the rabies-free country status in 2013, the last reported case of rabies being reported in a red fox in early 2011.[96][97] The United Kingdom has been free of rabies since the early 20th century except for a rabies-like virus in a few Daubenton's bats. There has been one fatal case of transmission to a human. There have been four deaths from rabies, transmitted abroad by dog bites, since 2000. The last infection in the UK occurred in 1922, and the last death from indigenous rabies was in 1902.[98][99] Unlike many of the other countries of Europe it is protected by being an island, and by strict quarantine procedures. ### Mexico Mexico was certified by the World Health Organization as free of dog-transmitted rabies in 2019, since no case of dog-human transmission has been recorded in two years.[100] ## History A woodcut from the Middle Ages showing a rabid dog. François Boissier de Sauvages de Lacroix, Della natura e causa della rabbia (Dissertation sur la nature et la cause de la Rage), 1777 Rabies has been known since around 2000 BC.[101] The first written record of rabies is in the Mesopotamian Codex of Eshnunna (circa 1930 BC), which dictates that the owner of a dog showing symptoms of rabies should take preventive measure against bites. If another person were bitten by a rabid dog and later died, the owner was heavily fined.[102] In Ancient Greece, rabies was supposed to be caused by Lyssa, the spirit of mad rage.[103] Accounts of vampires may have been exaggerated encounters with people suffering from rabies, as the disease causes symptoms similar to traits of vampires in legends, like pale skin and aggression. Ineffective folk remedies abounded in the medical literature of the ancient world. The physician Scribonius Largus prescribed a poultice of cloth and hyena skin; Antaeus recommended a preparation made from the skull of a hanged man.[104] Rabies appears to have originated in the Old World, the first epizootic in the New World occurring in Boston in 1768.[105] It spread from there, over the next few years, to various other states, as well as to the French West Indies, eventually becoming common all across North America. Rabies was considered a scourge for its prevalence in the 19th century. In France and Belgium, where Saint Hubert was venerated, the "St Hubert's Key" was heated and applied to cauterize the wound. By an application of magical thinking, dogs were branded with the key in hopes of protecting them from rabies. The fear of rabies was almost irrational, due to the number of vectors (mostly rabid dogs) and the absence of any efficacious treatment. It was not uncommon for a person bitten by a dog merely suspected of being rabid to commit suicide or to be killed by others.[106] In ancient times the attachment of the tongue (the lingual frenulum, a mucous membrane) was cut and removed as this was where rabies was thought to originate. This practice ceased with the discovery of the actual cause of rabies.[25] Louis Pasteur's 1885 nerve tissue vaccine was successful, and was progressively improved to reduce often severe side-effects.[15] In modern times, the fear of rabies has not diminished, and the disease and its symptoms, particularly agitation, have served as an inspiration for several works of zombie or similarly themed fiction, often portraying rabies as having mutated into a stronger virus which fills humans with murderous rage or incurable illness, bringing about a devastating, widespread pandemic.[107] ### Etymology The term is derived from the Latin rabies, "madness".[108] This, in turn, may be related to the Sanskrit rabhas, "to rage".[109] The Greeks derived the word lyssa, from lud or "violent"; this root is used in the genus name of the rabies virus, Lyssavirus.[106] ## Other animals Main article: Rabies in animals Rabies is infectious to mammals; three stages of central nervous system infection are recognized. The first stage is a one- to three-day period characterized by behavioral changes and is known as the prodromal stage. The second is the excitative stage, which lasts three to four days. This stage is often known as "furious rabies" for the tendency of the affected animal to be hyper-reactive to external stimuli and bite at anything near. The third is the paralytic stage and is caused by damage to motor neurons. Incoordination is seen, owing to rear limb paralysis, and drooling and difficulty swallowing is caused by paralysis of facial and throat muscles. Death is usually caused by respiratory arrest.[110] ## Research The outer shell of the rabies virus, stripped of its RNA contents and thus unable to cause disease, may be used as a vector for the delivery of unrelated genetic material in a research setting. It has the advantage over other pseudotyping methods for gene delivery that the cell targeting (tissue tropism) is more specific for the central nervous system, a difficult-to-reach site, obviating the need for invasive delivery methods. It is also capable of infecting neighboring "upstream" cells, moving from one cell to axons of the next at synapses, and is thus used for retrograde tracing in neuronal circuits.[111] Evidence indicates artificially increasing the permeability of the blood–brain barrier, which normally does not allow most immune cells across, promotes viral clearance.[112][113] ## See also * Viruses portal * Global Alliance for Rabies Control * Rabies in Haiti ## References 1. ^ a b c d e f g h i j k l m n o p q r s t u "Rabies Fact Sheet N°99". World Health Organization. July 2013. Archived from the original on 1 April 2014. Retrieved 28 February 2014. 2. ^ "Rabies - Symptoms and causes". Mayo Clinic. Retrieved 9 April 2018. 3. ^ a b c "Rabies, Australian bat lyssavirus and other lyssaviruses". The Department of Health. December 2013. Archived from the original on 4 March 2014. Retrieved 1 March 2014. 4. ^ a b Wang H, Naghavi M, Allen C, Barber RM, Bhutta ZA, Carter A, et al. (GBD 2015 Mortality and Causes of Death Collaborators) (October 2016). "Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1459–1544. doi:10.1016/s0140-6736(16)31012-1. PMC 5388903. PMID 27733281. 5. ^ a b c d Cotran RS, Kumar V, Fausto N (2005). Robbins and Cotran Pathologic Basis of Disease (7th ed.). Elsevier/Saunders. p. 1375. ISBN 978-0-7216-0187-8. 6. ^ a b c Tintinalli JE (2010). Emergency Medicine: A Comprehensive Study Guide (Emergency Medicine (Tintinalli)). McGraw-Hill. pp. Chapter 152. 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100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing 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[Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Rabies	c0034494	25,673	wikipedia	https://en.wikipedia.org/wiki/Rabies	2021-01-18T18:37:49	{"gard": ["7516"], "mesh": ["D011818"], "umls": ["C0034494"], "orphanet": ["770"], "wikidata": ["Q39222"]}
Dandy-Walker malformation affects brain development, primarily development of the cerebellum, which is the part of the brain that coordinates movement. In individuals with this condition, various parts of the cerebellum develop abnormally, resulting in malformations that can be observed with medical imaging. The central part of the cerebellum (the vermis) is absent or very small and may be abnormally positioned. The right and left sides of the cerebellum may be small as well. In affected individuals, a fluid-filled cavity between the brainstem and the cerebellum (the fourth ventricle) and the part of the skull that contains the cerebellum and the brainstem (the posterior fossa) are abnormally large. These abnormalities often result in problems with movement, coordination, intellect, mood, and other neurological functions. In the majority of individuals with Dandy-Walker malformation, signs and symptoms caused by abnormal brain development are present at birth or develop within the first year of life. Some children have a buildup of fluid in the brain (hydrocephalus) that may cause increased head size (macrocephaly). Up to half of affected individuals have intellectual disability that ranges from mild to severe, and those with normal intelligence may have learning disabilities. Children with Dandy-Walker malformation often have delayed development, particularly a delay in motor skills such as crawling, walking, and coordinating movements. People with Dandy-Walker malformation may experience muscle stiffness and partial paralysis of the lower limbs (spastic paraplegia), and they may also have seizures. While rare, hearing and vision problems can be features of this condition. Less commonly, other brain abnormalities have been reported in people with Dandy-Walker malformation. These abnormalities include an underdeveloped or absent tissue connecting the left and right halves of the brain (agenesis of the corpus callosum), a sac-like protrusion of the brain through an opening at the back of the skull (occipital encephalocele), or a failure of some nerve cells (neurons) to migrate to their proper location in the brain during development. These additional brain malformations are associated with more severe signs and symptoms. Dandy-Walker malformation typically affects only the brain, but problems in other systems can include heart defects, malformations of the urogenital tract, extra fingers or toes (polydactyly) or fused fingers or toes (syndactyly), or abnormal facial features. In 10 to 20 percent of people with Dandy-Walker malformation, signs and symptoms of the condition do not appear until late childhood or into adulthood. These individuals typically have a different range of features than those affected in infancy, including headaches, an unsteady walking gait, paralysis of facial muscles (facial palsy), increased muscle tone, muscle spasms, and mental and behavioral changes. Rarely, people with Dandy-Walker malformation have no health problems related to the condition. Problems related to hydrocephalus or complications of its treatment are the most common cause of death in people with Dandy-Walker malformation. ## Frequency Dandy-Walker malformation is estimated to affect 1 in 10,000 to 30,000 newborns. ## Causes Researchers have found mutations in a few genes that are thought to cause Dandy-Walker malformation, but these mutations account for only a small number of cases. Dandy-Walker malformation has also been associated with many chromosomal abnormalities. This condition can be a feature of some conditions in which there is an extra copy of one chromosome in each cell (trisomy). Dandy-Walker malformation most often occurs in people with trisomy 18 (an extra copy of chromosome 18), but can also occur in people with trisomy 13, trisomy 21, or trisomy 9. This condition can also be associated with missing (deletions) or copied (duplications) pieces of certain chromosomes. Dandy-Walker malformation can also be a feature of genetic syndromes that are caused by mutations in specific genes. However, the brain malformations associated with Dandy-Walker malformation often occur as an isolated feature (not associated with other health problems), and in these cases the cause is frequently unknown. Research suggests that Dandy-Walker malformation could be caused by environmental factors that affect early development before birth. For example, exposure of the fetus to substances that cause birth defects (teratogens) may be involved in the development of this condition. In addition, a mother with diabetes is more likely than a healthy mother to have a child with Dandy-Walker malformation. ### Learn more about the gene associated with Dandy-Walker malformation * FOXC1 Additional Information from NCBI Gene: * ZIC1 * ZIC4 ## Inheritance Pattern Most cases of Dandy-Walker malformation are sporadic, which means they occur in people with no history of the disorder in their family. A small percentage of cases seem to run in families; however, Dandy-Walker malformation does not have a clear pattern of inheritance. Multiple genetic and environmental factors likely play a part in determining the risk of developing this disorder. First-degree relatives (such as siblings and children) of people with Dandy-Walker malformation have an increased risk of developing the condition compared with people in the general population. When Dandy-Walker malformation is a feature of a genetic condition, it is inherited in the pattern of that condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Dandy-Walker malformation	c0010964	25,674	medlineplus	https://medlineplus.gov/genetics/condition/dandy-walker-malformation/	2021-01-27T08:25:47	{"gard": ["6242"], "mesh": ["D003616"], "omim": ["220200"], "synonyms": []}
This article has multiple issues. Please help improve it or discuss these issues on the talk page. (Learn how and when to remove these template messages) This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Major depressive episode" – news · newspapers · books · scholar · JSTOR (April 2014) (Learn how and when to remove this template message) This article may have too many section headers dividing up its content. Please help improve the article by merging similar sections and removing unneeded subheaders. (November 2013) (Learn how and when to remove this template message) (Learn how and when to remove this template message) Major depressive episode SpecialtyPsychiatry A major depressive episode (MDE) is a period characterized by the symptoms of major depressive disorder. Sufferers primarily have a depressed mood for two weeks or more, and a loss of interest or pleasure in everyday activities, accompanied by other symptoms such as feelings of emptiness, hopelessness, anxiety, worthlessness, guilt and irritability, changes in appetite, problems concentrating, remembering details or making decisions, and thoughts of suicide.[1] Insomnia or hypersomnia, aches, pains, or digestive problems that are resistant to treatment may also be present.[1] The description has been formalized in psychiatric diagnostic criteria such as the DSM-5 and ICD-10.[2][full citation needed] Biological, psychological, and social factors are believed to be involved in the cause of depression, although it is still not well understood.[3] Factors like socioeconomic status, life experience, and personality tendencies play a role in the development of depression and may represent increases in risk for developing a major depressive episode.[4] There are many theories as to how depression occurs. One interpretation is that neurotransmitters in the brain are out of balance, and this results in feelings of worthlessness and despair. Magnetic resonance imaging shows that brains of people who have depression look different than the brains of people not exhibiting signs of depression.[5] A family history of depression increases the chance of being diagnosed.[6] Emotional pain and economic costs are associated with depression. In the United States and Canada, the costs associated with major depression are comparable to those related to heart disease, diabetes, and back problems and are greater than the costs of hypertension.[7] According to the Nordic Journal of Psychiatry, there is a direct correlation between major depressive episode and unemployment.[8] Treatments for a major depressive episode include psychotherapy and antidepressants, although in more serious cases, hospitalization or intensive outpatient treatment may be required.[9] ## Contents * 1 Signs and symptoms * 1.1 Depressed mood and loss of interest (anhedonia) * 1.2 Sleep * 1.3 Feelings of guilt or worthlessness * 1.4 Loss of energy * 1.5 Decreased concentration * 1.6 Change in eating, appetite, or weight * 1.7 Motor activity * 1.8 Thoughts of death and suicide * 1.9 Comorbid disorders * 2 Causes * 3 Diagnosis * 3.1 Criteria * 3.2 Workup * 3.3 Differential Diagnosis * 4 Screening * 5 Treatment * 5.1 Therapy * 5.2 Medication * 5.3 Alternative treatments * 6 Prognosis * 7 Epidemiology * 8 See also * 9 Notes * 10 External links ## Signs and symptoms[edit] The criteria below are based on the formal DSM-V criteria for a major depressive episode. A diagnosis of major depressive episode requires that the patient has experienced five or more of the symptoms below, and one of the symptoms must be either depressed mood or loss of interest or pleasure (although both are frequently present).[1] These symptoms must be present for at least 2 weeks and represent a change from the patient's normal behavior.[1] ### Depressed mood and loss of interest (anhedonia)[edit] Either depressed mood or a loss of interest or pleasure must be present for the diagnosis of a major depressive episode.[1] Depressed mood is the most common symptom seen in major depressive episodes.[4] Interest or pleasure in everyday activities can be decreased; this is referred to as anhedonia. These feelings must be present on an everyday basis for two weeks or longer to meet DSM-V criteria for a major depressive episode.[1] In addition, the person may experience one or more of the following emotions: sadness, emptiness, hopelessness, indifference, anxiety, tearfulness, pessimism, emotional numbness, or irritability.[1][4] In children and adolescents, a depressed mood often appears more irritable in nature.[1] There may be a loss of interest in or desire for sex, or other activities once found to be pleasant.[1] Friends and family of the depressed person may notice that they have withdrawn from friends, or neglected or quit doing activities that were once a source of enjoyment.[10] ### Sleep[edit] Nearly every day, the person may sleep excessively, known as hypersomnia, or not enough, known as insomnia.[11] Insomnia is the most common type of sleep disturbance for people who are clinically depressed.[4] Symptoms of insomnia include trouble falling asleep, trouble staying asleep, or waking up too early in the morning.[4] Hypersomnia is a less common type of sleep disturbance. It may include sleeping for prolonged periods at night or increased sleeping during the daytime.[4] The sleep may not be restful, and the person may feel sluggish despite many hours of sleep, which may amplify their depressive symptoms and interfere with other aspects of their lives.[4] Hypersomnia is often associated with an atypical depression, as well as seasonal affective disorder.[10] ### Feelings of guilt or worthlessness[edit] Depressed people may have feelings of guilt that go beyond a normal level or are delusional.[1] These feelings of guilt and/or worthlessness are excessive and inappropriate.[1] Major depressive episodes are notable for a significant, often unrealistic, drop in self-esteem.[4] The guilt and worthlessness experienced in a major depressive episode can range from subtle feelings of guilt to frank delusions or to shame and humiliation.[4] Additionally, self-loathing is common in clinical depression, and can lead to a downward spiral when combined with other symptoms.[10] ### Loss of energy[edit] Persons going through a major depressive episode often have a general lack of energy, as well as fatigue and tiredness,[4] nearly every day for at least 2 weeks.[1] A person may feel tired without having engaged in any physical activity, and day-to-day tasks become increasingly difficult. Job tasks or housework become very tiring, and the patient finds that their work begins to suffer.[10] ### Decreased concentration[edit] Nearly every day, the person may be indecisive or have trouble thinking or concentrating.[11] These issues cause significant difficulty in functioning for those involved in intellectually demanding activities, such as school and work, especially in difficult fields.[10] Depressed people often describe a slowing of thought, inability to concentrate and make decisions, and being easily distracted.[4] In the elderly, the decreased concentration caused by a major depressive episode may present as deficits in memory.[4] This is referred to as pseudodementia and often goes away with treatment.[4] Decreased concentration may be reported by the patient or observed by others.[1] ### Change in eating, appetite, or weight[edit] In a major depressive episode, appetite is most often decreased, although a small percentage of people experience an increase in appetite.[4] A person experiencing a depressive episode may have a marked loss or gain of weight (5% of their body weight in one month).[11] A decrease in appetite may result in weight loss that is unintentional or when a person is not dieting.[4] Some people experience an increase in appetite and may gain significant amounts of weight. They may crave certain types of food, such as sweets or carbohydrates.[4] In children, failure to make expected weight gains may be counted towards this criteria.[1] Overeating is often associated with atypical depression.[10] ### Motor activity[edit] Nearly every day, others may see that the person's activity level is not normal.[11] People suffering from depression may be overly active (psychomotor agitation) or be very lethargic (psychomotor retardation).[1] Psychomotor agitation is marked by an increase in body activity which may result in restlessness, an inability to sit still, pacing, hand wringing, or fidgeting with clothes or objects.[4] Psychomotor retardation results in a decrease in body activity or thinking.[4] In this case, a depressed person may demonstrate a slowing of thinking, speaking, or body movement.[4] They may speak more softly or say less than usual. To meet diagnostic criteria, changes in motor activity must be so abnormal that it can be observed by others.[10] Personal reports of feeling restless or feeling slow do not count towards the diagnostic criteria.[1] ### Thoughts of death and suicide[edit] A person going through a major depressive episode may have repeated thoughts about death (other than the fear of dying) or suicide (with or without a plan), or may have made a suicide attempt.[11] The frequency and intensity of thoughts about suicide can range from believing that friends and family would be better off if one were dead, to frequent thoughts about committing suicide (generally related to wishing to stop the emotional pain), to detailed plans about how the suicide would be carried out.[4] Those who are more severely suicidal may have made specific plans and decided upon a day and location for the suicide attempt.[10] ### Comorbid disorders[edit] Major depressive episodes may show comorbidity (association) with other physical and mental health problems. About 20–25% of individuals with a chronic general medical condition will develop major depression.[7] Common comorbid disorders include: eating disorders, substance-related disorders, panic disorder, and obsessive-compulsive disorder. Up to 25% of people who experience a major depressive episode have a pre-existing dysthymic disorder.[7] Some persons who have a fatal illness or are at the end of their life may experience depression, although this is not universal.[12] ## Causes[edit] The cause of a major depressive episode is not well understood.[13] However, the mechanism is believed to be a combination of biological, psychological, and social factors.[3] A major depressive episode can often follow an acute stress in someone's life.[4] Evidence suggests that psychosocial stressors play a larger role in the first 1-2 depressive episodes, while having less influence in later episodes.[4] People who experience a major depressive episode often have other mental health issues.[13] Other risk factors for a depressive episode include:[4] * Family history of a mood disorder * Recent negative life events * Personality (insecure, worried, stress-sensitive, obsessive, unassertive, dependent) * Early childhood trauma * Postpartum * Lack of interpersonal relationships One gene by itself has not been linked to depression. Studies show that depression can be passed down in families, but this is believed to be due to a combined effect of genetic and environmental factors.[13] Other medical conditions, like hypothyroidism for example, may cause someone to experience similar symptoms as a major depressive episode,[14] however this would be considered a mood disorder due to a general medical condition, according to the DSM-V.[1] ## Diagnosis[edit] ### Criteria[edit] The two main symptoms in a major depressive episode are a depressed mood or a loss of interest or pleasure.[15] From the list below, one bold symptom and four other symptoms must be present for a diagnosis of major depressive episode. These symptoms must be present for at least 2 weeks and must be causing significant distress or impairment in functioning.[15] * Depressed mood * Loss of interest or pleasure * Change in appetite * Change in sleep * Change in body activity (psychomotor changes) * Loss of energy * Feelings of worthlessness and excessive or inappropriate guilt * Indecisiveness or a decrease in concentration * Suicidal ideation To diagnose a major depressive episode, a trained healthcare provider must make sure that: * The symptoms do not meet the criteria for a mixed episode.[2] * The symptoms must cause considerable distress or impair functioning at work, in social settings or in other important areas in order to qualify as an episode.[2] * The symptoms are not due to the direct physiological effects of a substance (e.g., abuse of a drug or medication) or a general medical condition (e.g., hypothyroidism).[2] ### Workup[edit] No labs are diagnostic of a depressive episode.[15] But some labs can help rule out general medical conditions that may mimic the symptoms of a depressive episode. Healthcare providers may order some routine blood work, including routine blood chemistry, CBC with differential, thyroid function studies, and Vitamin B12 levels, before making a diagnosis.[16] ### Differential Diagnosis[edit] There are other mental health disorders or medical conditions to consider before diagnosing a major depressive episode:[16][9] * Bipolar disorder * Cyclothymic disorder * Disruptive mood dysregulation disorder * Persistent depressive disorder * Anxiety disorder (Generalized anxiety, PTSD, obsessive compulsive disorder) * Substance abuse or Substance Use Disorder * Personality disorder with depressive symptoms * Adjustment disorder * Depression due to a general medical condition * Premenstrual dysphoric disorder ## Screening[edit] Healthcare providers may screen patients in the general population for depression using a screening tool, such as the Patient Healthcare Questionnaire-2 (PHQ-2).[17] If the PHQ-2 screening is positive for depression, a provider may then administer the PHQ-9.[16] The Geriatric Depression Scale is a screening tool that can be used in the elderly population.[16] ## Treatment[edit] Depression is a treatable illness. Treatments for a major depressive episode may be provided by mental health specialists (i.e. psychologist, psychiatrists, social workers, counselors, etc.), mental health centers or organizations, hospitals, outpatient clinics, social service agencies, private clinics, peer support groups, clergy, and employee assistance programs.[18] The treatment plan could include psychotherapy alone, antidepressant medications alone, or a combination of medication and psychotherapy.[18] For major depressive episodes of severe intensity (multiple symptoms, minimal mood reactivity, severe functional impairment), combined psychotherapy and antidepressant medications are more effective than psychotherapy alone.[2] Meta-analyses suggest that the combination of psychotherapy and antidepressant medications is more effective in treating mild and moderate forms of depression as well, compared to either type of treatment alone.[19] Patients with severe symptoms may require outpatient treatment or hospitalization.[9] The treatment of a major depressive episode can be split into 3 phases:[19] 1. Acute phase: the goal of this phase is to resolve the current major depressive episode 2. Continuation: this phase continues the same treatment from the acute phase for 4–8 months after the depressive episode has resolved and the goal is to prevent relapse 3. Maintenance: this phase is not necessary for every patient but is often used for patients who have experienced 2–3 or more major depressive episodes. Treatment may be maintained indefinitely to prevent the occurrence and severity of future episodes. ### Therapy[edit] Psychotherapy, also known as talk therapy, counseling, or psychosocial therapy, is characterized by a patient talking about their condition and mental health issues with a trained therapist. Different types of psychotherapy are used as a treatment for depression. These include cognitive behavioral therapy, interpersonal therapy, dialectical behavior therapy, acceptance and commitment therapy, and mindfulness techniques.[9] Evidence shows that cognitive behavioral therapy can be as effective as medication in the treatment of a major depressive episode.[16] Psychotherapy may be the first treatment used for mild to moderate depression, especially when psychosocial stressors are playing a large role.[19] Psychotherapy alone may not be as effective for more severe forms of depression.[19] Some of the main forms of psychotherapies used for treatment of a major depressive episode along with what makes them unique are included below:[19] * Cognitive psychotherapy: focus on patterns of thinking * Interpersonal psychotherapy: focus on relationships, losses, and conflict resolution * Problem-solving psychotherapy: focus on situations and strategies for problem-solving * Psychodynamic psychotherapy: focus on defense mechanisms and coping strategies ### Medication[edit] Prozac is one example of an SSRI, the class of antidepressant medications that is used as the first line in treatment of depression. Medications used to treat depression include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), norepinephrine-dopamine reuptake inhibitors (NDRIs), tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs), and atypical antidepressants such as mirtazapine, which do not fit neatly into any of the other categories.[9] Different antidepressants work better for different individuals. It is often necessary to try several before finding one that works best for a specific patient. Some people may find it necessary to combine medications, which could mean two antidepressants or an antipsychotic medication in addition to an antidepressant.[20] If a person's close relative has responded well to a certain medication, that treatment will likely work well for him or her.[9] Antidepressant medications are effective in the acute, continuation, and maintenance phases of treatment, as described above.[19] The treatment benefits of antidepressant medications are often not seen until 1–2 weeks into treatment, with maximum benefits being reached around 4–6 weeks.[19] Most healthcare providers will monitor patients more closely during the acute phase of treatment and continue to monitor at longer intervals in the continuation and maintenance phases.[19] Sometimes, people stop taking antidepressant medications due to side effects, although side effects often become less severe over time.[20] Suddenly stopping treatment or missing several doses may cause withdrawal-like symptoms.[9] Some studies have shown that antidepressants may increase short-term suicidal thoughts or actions, especially in children, adolescents, and young adults. However, antidepressants are more likely to reduce a person's risk of suicide in the long run.[9] Below are listed the main classes of antidepressant medications, some of the most common drugs in each category, and their major side effects:[19] * Selective serotonin reuptake inhibitors (citalopram, escitalopram, paroxetine, fluoxetine, sertraline): major side effects include nausea, diarrhea, and sexual dysfunction * Serotinin and norepinephrine reuptake inhibitors (duloxetine, venlafaxine, desvenlafaxine): major side effects include nausea, diarrhea, increased heart rate, increased blood pressure, and tremor * Tricyclic antidepressants (amitryptiline, desipramine, doxepin, imipramine, nortriptyline): major side effects include sedation, low blood pressure when moving from sitting to standing (orthostatic hypotension), tremor, and heart issues like conduction delays or arrythmias * Monoamine oxidase inhibitors (isocarboxazid, phenelzine, selegiline): major side effects include high blood pressure (emergency) if eaten with foods rich in tyramine (e.g. cheeses, some meats, and home-brewed beer), sedation, tremor, and orthostatic hypotension ### Alternative treatments[edit] There are several treatment options that exist for people who have experienced several episodes of major depression or have not responded to several treatments. Electroconvulsive therapy is a treatment in which a generalized seizure is induced by means of electrical current.[21] The mechanism of action of the treatment is not clearly understood[21] but has been show to be most effective in the most severely depressed patients.[15] For this reason, electroconvulsive therapy is preferred for the most severe forms of depression or depression that has not responded to other treatments, known as refractory depression.[19] Vagus nerve stimulation is another alternative treatment that has been proven to be effective in the treatment of depression, especially people that have been resistant to four or more treatments.[15] Some of the unique benefits of vagus nerve stimulation include improved neurocognitive function and a sustained clinical response.[15] Transcranial magnetic stimulation is also an alternative treatment for a major depressive episode.[15] It is a noninvasive treatment that is easily tolerated and shows an antidepressant effect, especially in more typical depression and younger adults.[15] ## Prognosis[edit] If left untreated, a typical major depressive episode may last for several months.[22] About 20% of these episodes can last two years or more. About half of depressive episodes end spontaneously. However, even after the major depressive episode is over, 20% to 30% of patients have residual symptoms, which can be distressing and associated with disability.[7] Fifty percent of people will have another major depressive episode after the first.[15] However, the risk of relapse is decreased by taking antidepressant medications for more than 6 months.[15] Symptoms completely improve in six to eight weeks in sixty to seventy percent of patients.[23] The combination of therapy and antidepressant medications has been shown to improve resolution of symptoms and outcomes of treatment.[23] Suicide is the 8th leading cause of death in the United States.[15] The risk of suicide is increased during a major depressive episode. However, the risk is even more elevated during the first two phases of treatment.[15] There are several factors associated with an increased risk of suicide, listed below:[15][24] * Greater than 45 years of age * Male * History of suicide attempt or self-injurious behaviors * Family history of suicide or mental illness * Recent severe loss * Poor health * Detailed plan * Inability to accept help * Lack of social support * Psychotic features (auditory or visual hallucinations, disorganization of speech, behavior, or thought) * Alcohol or drug use or comorbid psychiatric disorder * Severe depression ## Epidemiology[edit] Estimates of the numbers of people suffering from major depressive episodes and major depressive disorder (MDD) vary significantly. Overall, 13-20% of people will experience significant depressive symptoms at some point in their life.[4] The overall prevalence of MDD is slightly lower ranging from 3.7-6.7% of people.[4] In their lifetime, 20% to 25% of women, and 7% to 12% of men will suffer a major depressive episode.[25] The peak period of development is between the ages of 25 and 44 years.[4] Onset of major depressive episodes or MDD often occurs to people in their mid-20s, and less often to those over 65. The prevalence of depressive symptoms in the elderly is around 1-2%.[25] Elderly persons in nursing homes may have increased rates, up to 15-25%.[25] African-Americans have higher rates of depressive symptoms compared to other races.[26] Prepubescent girls are affected at a slightly higher rate than prepubescent boys.[26] In a National Institute of Mental Health study, researchers found that more than 40% of people with post-traumatic stress disorder suffered from depression four months after the traumatic event they experienced.[27] Women who have recently given birth may be at increased risk for having a major depressive episode. This is referred to as postpartum depression and is a different health condition than the baby blues, a low mood that resolves within 10 days after delivery.[12] ## See also[edit] * Depressive personality disorder * Depression (differential diagnoses) * Major depressive disorder * Mental breakdown ## Notes[edit] 1. ^ a b c d e f g h i j k l m n o p q Diagnostic and statistical manual of mental disorders : DSM-5. American Psychiatric Association., American Psychiatric Association. DSM-5 Task Force. (5th ed.). Arlington, VA: American Psychiatric Association. 2013. ISBN 9780890425541. OCLC 830807378.CS1 maint: others (link) 2. ^ a b c d e Diagnostic and Statistical Manual of Mental Disorders, fourth Edition 3. ^ a b HASLER, GREGOR (October 2010). "PATHOPHYSIOLOGY OF DEPRESSION: DO WE HAVE ANY SOLID EVIDENCE OF INTEREST TO CLINICIANS?". World Psychiatry. 9 (3): 155–161. doi:10.1002/j.2051-5545.2010.tb00298.x. ISSN 1723-8617. PMC 2950973. PMID 20975857. 4. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z "Current Diagnosis & Treatment: Psychiatry, 3e \| AccessMedicine \| McGraw-Hill Medical". accessmedicine.mhmedical.com. Retrieved 2018-11-26. 5. ^ Katon, Wayne; Ciechanowski, Paul (October 2002). "Impact of major depression on chronic medical illness". Journal of Psychosomatic Research. 53 (4): 859–863. doi:10.1016/s0022-3999(02)00313-6. PMID 12377294. 6. ^ Tsuang, Ming T.; Bar, Jessica L.; Stone, William S.; Faraone, Stephen V. (June 2004). "Gene-environment interactions in mental disorders". World Psychiatry. 3 (2): 72–83. PMC 1414673. PMID 16633461. 7. ^ a b c d Valdivia, Ivan; Rossy, Nadine (2004). "Brief Treatment Strategies for Major Depressive Disorder: Advice for the Primary Care Clinician". Topics in Advanced Practice Nursing eJournal. 4 (1) – via Medscape. 8. ^ Hämäläinen, Juha; Poikolainen, Kari; Isometsa, Erkki; Kaprio, Jaakko; Heikkinen, Martti; Lindeman, Sari; Aro, Hillevi (2005). "Major depressive episode related to long unemployment and frequent alcohol intoxication". Nordic Journal of Psychiatry. 59 (6): 486–491. doi:10.1080/08039480500360872. PMID 16316902. 9. ^ a b c d e f g h "Depression (major depression)". Mayo Clinic. Retrieved February 13, 2015. 10. ^ a b c d e f g h "All About Depression: Diagnosis". All About Depression.com. www.allaboutdepression.com. Archived from the original on 13 February 2015. Retrieved 13 February 2015. 11. ^ a b c d e "Criteria for Major Depressive Episode". Winthrop University. faculty.winthrop.edu. Archived from the original on 23 November 2005. Retrieved 20 November 2013. 12. ^ a b Hirst, KP; Moutier, CY (15 October 2010). "Postpartum major depression". American Family Physician. 82 (8): 926–933. PMID 20949886. 13. ^ a b c Walls, Ron M., MD; Hockberger, Robert S., MD; Gausche-Hill, Marianne, MD, FACEP, FAAP, FAEMS (2018). Rosen's Emergency Medicine: Concepts and Clinical Practice, Ninth Edition. Elsevier.CS1 maint: multiple names: authors list (link) 14. ^ Stern, Theodore A., MD; Fava, Maurizio, MD; Wilens, Timothy E., MD; Rosenbaum, Jerrold F., MD (2016). Massachusetts General Hospital Comprehensive Clinical Psychiatry, Second Edition. Elsevier.CS1 maint: multiple names: authors list (link) 15. ^ a b c d e f g h i j k l m Michael H. Ebert, James F. Leckman, Ismene L. Petrakis (2018). "Current Diagnosis & Treatment: Psychiatry, 3e \| AccessMedicine \| McGraw-Hill Medical". accessmedicine.mhmedical.com.CS1 maint: multiple names: authors list (link) 16. ^ a b c d e Ferri, Fred F., M.D., F.A.C.P. (2019). Ferri's Clinical Advisor 2019. Elsevier.CS1 maint: multiple names: authors list (link) 17. ^ Maurer, DM (15 January 2012). "Screening for depression". American Family Physician. 85 (2): 139–144. PMID 22335214. 18. ^ a b Cassano, P (2002). "Depression and public health, an overview". Journal of Psychosomatic Research. 53 (4): 849–857. doi:10.1016/s0022-3999(02)00304-5. PMID 12377293. 19. ^ a b c d e f g h i j Goldman, Lee, MD; Schafer, Andrew I., MD (2016). Goldman-Cecil Medicine. Saunders.CS1 maint: multiple names: authors list (link) 20. ^ a b "Depression Medicines". WebMD. Retrieved February 13, 2015. 21. ^ a b Raj, Kristin S.; Williams, Nolan; DeBattista, Charles (2019), Papadakis, Maxine A.; McPhee, Stephen J.; Rabow, Michael W. (eds.), "Psychiatric Disorders", Current Medical Diagnosis & Treatment 2019, McGraw-Hill Education, retrieved 2018-12-06 22. ^ "Major Depression". Harvard Medical School. Retrieved 14 October 2020. 23. ^ a b medicine., Kasper, Dennis L., editor. Harrison, Tinsley Randolph, 1900-1978. Manual of (2016-05-27). Harrison's manual of medicine. ISBN 9780071828529. OCLC 962405754. 24. ^ Hawton, Keith; Casañas i Comabella, Carolina; Haw, Camilla; Saunders, Kate (2013-05-01). "Risk factors for suicide in individuals with depression: A systematic review". Journal of Affective Disorders. 147 (1–3): 17–28. doi:10.1016/j.jad.2013.01.004. ISSN 0165-0327. PMID 23411024. 25. ^ a b c Mitchell D. Feldman, John F. Christensen, Jason M. Satterfield (2014). Behavioral Medicine: A Guide for Clinical Practice, 4e. McGraw-Hill.CS1 maint: multiple names: authors list (link) 26. ^ a b Younger, David S. (2016-11-01). "Epidemiology of Childhood and Adult Mental Illness". Neurologic Clinics. 34 (4): 1023–1033. doi:10.1016/j.ncl.2016.06.010. ISSN 0733-8619. PMID 27719986. 27. ^ Shalev, A; Freedman, S; Peri, T; Brandes, D; Sahar, T; Orr, SP; Pitman, RK (May 1998). "Prospective study of posttraumatic stress disorder and depression following trauma". American Journal of Psychiatry. 155 (5): 630–637. doi:10.1176/ajp.155.5.630. PMID 9585714. ## External links[edit] * Depression information from the National Institutes of Health Classification D * ICD-10: F32.2-F32.3 * ICD-9-CM: 296.2 * v * t * e Mood disorder History * Emil Kraepelin * Karl Leonhard * John Cade * Mogens Schou * Frederick K. Goodwin * Kay Redfield Jamison Symptoms * Hallucination * Delusion * Emotional dysregulation * Anhedonia * Dysphoria * Suicidal ideation * Mood swing * Sleep disorder * Hypersomnia * Insomnia * Psychosis * Racing thoughts * Reduced affect display * Depression (differential diagnoses) Spectrum * Bipolar disorder * Bipolar I * Bipolar II * Cyclothymia * Bipolar NOS * Depression * Major depressive disorder * Dysthymia * Seasonal affective disorder * Atypical depression * Melancholic depression * Schizoaffective disorder * Mania * Mixed affective state * Hypomania * Major depressive episode * Rapid cycling Treatment Anticonvulsants * Carbamazepine * Lamotrigine * Oxcarbazepine * Valproate * Sodium valproate * Valproate semisodium Sympathomimetics, SSRIs and similar * Dextroamphetamine * Methylphenidate * Bupropion * Sertraline * Fluoxetine * Escitalopram Other mood stabilizers * Antipsychotics * Lithium * Lithium carbonate * Lithium citrate * Lithium sulfate * Lithium toxicity * Atypical antipsychotics Non-pharmaceutical * Clinical psychology * Electroconvulsive therapy * Involuntary commitment * Light therapy * Psychotherapy * Transcranial magnetic stimulation * Cognitive behavioral therapy * Dialectical behavior therapy [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Major depressive episode	c0024517	25,675	wikipedia	https://en.wikipedia.org/wiki/Major_depressive_episode	2021-01-18T19:08:31	{"icd-9": ["296.2"], "icd-10": ["F32.2", "F32.3"], "wikidata": ["Q6738337"]}
A number sign (#) is used with this entry because familial temporal lobe epilepsy-5 (ELT5) is caused by heterozygous mutation in the CPA6 gene (609562) on chromosome 8q13. One patient with compound heterozygous mutations has been reported. For a general description and a discussion of genetic heterogeneity of familial temporal lobe epilepsy, see 600512. Clinical Features Salzmann et al. (2012) reported 3 unrelated Caucasian patients, aged 39, 42, and 49 years, with temporal lobe epilepsy. Two had onset at ages 23 and 5 years, respectively; information about age at onset was not available for the third patient. Seizures could be localized to the temporoparietal junction in 1 patient. One patient had neonatal sequelae, which was not further explained, another had bitemporal atrophy on MRI, and a third had a cavernous malformation. None had a history of febrile seizures, although 1 patient had a paternal grandfather with a reported history of febrile seizures. Sapio et al. (2012) reported a 20-year-old man (ET174) with ETL5. He had onset of seizures at age 7 and was found to have hippocampal sclerosis. Molecular Genetics In 3 unrelated patients with temporal lobe epilepsy, Salzmann et al. (2012) identified a heterozygous mutation in the CPA6 gene (G267R; 609562.0002). The patients were ascertained from a larger cohort of 195 patients with partial epilepsy and 145 with febrile seizures who were screened for mutations in the CPA6 gene after this gene was found to be a cause of autosomal recessive febrile seizures (FEB11; 614418). In vitro functional expression studies in cellular assays showed that the mutant protein had decreased activity compared to wildtype due to impaired secretion into the extracellular matrix. Those heterozygous for the G267R mutation would have about 50% residual enzyme activity, consistent with a loss of function. In 1 of the patients (ET158) originally reported by Salzmann et al. (2012) as having a heterozygous G267R mutation in the CPA6 gene, Sapio et al. (2012) identified a second heterozygous missense mutation in the CPA6 gene (Q207E; 609562.0003). Parental DNA was not available for segregation analysis. Expression of the Q207E mutation in HEK293 cells showed that the mutant protein had only 11% residual enzyme activity compared to wildtype, and the mutant protein was not detected in the extracellular matrix. Sapio et al. (2012) also identified a heterozygous missense mutation in the CPA6 gene (H196R; 609562.0004) in an unrelated patient with ETL5. Parental DNA was not available for segregation analysis. Expression of the H196R mutation in HEK293 cells showed that the mutant protein had no enzyme activity, but was expressed at very low levels in the extracellular matrix. There was no evidence of a dominant-negative effect when coexpressed with the wildtype protein. INHERITANCE \- Autosomal dominant \- Autosomal recessive (in 1 patient) NEUROLOGIC Central Nervous System \- Seizures, temporal lobe \- Structural changes in the temporal lobe MISCELLANEOUS \- Variable age of onset \- Four unrelated Caucasian patients have been reported (as of March 2017) \- One patient had compound heterozygous mutations MOLECULAR BASIS \- Caused by mutation in the carboxypeptidase A6 gene (CPA6, 609562.0002 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	EPILEPSY, FAMILIAL TEMPORAL LOBE, 5	c3280730	25,676	omim	https://www.omim.org/entry/614417	2019-09-22T15:55:21	{"doid": ["0060752"], "omim": ["614417"], "orphanet": ["163717"], "synonyms": ["Benign FMTLE"]}
A number sign (#) is used with this entry because X-linked retinitis pigmentosa-2 (RP2) is caused by mutation in the RP2 gene (300757) on chromosome Xp11. Description Retinitis pigmentosa is characterized by constriction of the visual fields, night blindness, and fundus changes, including 'bone corpuscle' lumps of pigment. RP unassociated with other abnormalities is inherited most frequently (84%) as an autosomal recessive, next as an autosomal dominant (10%), and least frequently (6%) as an X-linked recessive in the white U.S. population (Boughman et al., 1980). For a general phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000. Clinical Features The X-linked form of retinitis pigmentosa is also called choroidoretinal degeneration, or pigmentary retinopathy. The gyrate choroidal atrophy described by Waardenburg (1932) as X-linked was found on further study to be retinitis pigmentosa (Waardenburg et al., 1961). As pointed out in a review by Jacobson and Stephens (1962), there are some phenotypic differences between reported families. The genetic significance of these differences is unknown. There may be a fully recessive and an intermediate X-linked form. Affected males show typical 'bone corpuscle' clumps of pigment on funduscopic examination and progressive choroidal sclerosis leading to complete blindness. Hoare (1965) described a choroidoretinal disorder in 10 males in 7 sibships who were offspring of sisters. The maternal grandfather of the affected males was probably also affected. The condition was detected in childhood. Some carrier women showed fundus abnormalities with visual impairment beginning in middle age and probably showing progression. The condition in males resembled retinitis pigmentosa in fundus picture and night blindness, but differed by the absence of annular scotoma, by early involvement of central vision, and by relatively little vascular change. In fact, many males with RP2 show choroidoretinal atrophy in the advanced stages (Bird, 1975). In 21 females heterozygous for X-linked RP (XLRP), Ernst et al. (1981) found reduced flicker sensitivity over the whole frequency range where thresholds could be tested. Bundey and Crews (1986) concluded that the likelihood of an isolated male with severe retinitis pigmentosa having the X-linked form is about 1 in 2; of 74 male index patients, 21 had X-linked disease. In the family reported by Heck (1963), some heterozygous females were fully affected and some showed only a blue-yellow color defect (a rare anomaly). 'Tapetal reflex' was not present. The type of retinal degeneration was variable, being pigmentary, nonpigmentary, or macular in different affected males. Cataract was present in 2 with pigmentary degeneration. Fishman et al. (1988) profiled the clinical findings in 56 patients with X-linked retinitis pigmentosa from 35 families. Ultrastructural observations suggested that the rod photoreceptors are severely affected by the mutation in this disorder. Because photoreceptors develop from ciliated progenitors, it has been suggested that the axoneme may play a role in the development of photoreceptors. For this reason, Hunter et al. (1988) studied sperm axoneme structure in 8 patients with X-linked retinitis pigmentosa. A significant increase in the percentage of abnormal sperm tails was observed. Similar observations have been reported in Usher syndrome (276900). Kaplan et al. (1990) suggested that phenotypically there are 2 forms of X-linked RP: one form has very early onset with severe myopia (mean age of onset = 3.5 years; 1 SD = 0.05); the other form starts later with night blindness with or without mild myopia (mean age of onset = 10.6 years; 1 SD = 4.1). Kaplan et al. (1992) presented linkage evidence that the clinical form with early myopia as the initial symptom is associated with the RP2 gene, while the clinical form with later night blindness as the initial symptom is associated with the RP3 gene. Friedrich et al. (1993) found on reexamination of 7 obligate carrier females and 6 daughters of obligate carriers whose linkage relationships suggested that they carried the RP2 gene that the phenotype varied from totally normal eyes through mild retinal changes to complete loss of vision. Grover et al. (2000) evaluated the progression of visual impairment in carriers of X-linked recessive retinitis pigmentosa. They described the relationship between retinal findings at presentation and the extent of subsequent deterioration. They followed visual acuity, visual field, and electroretinograms (ERG) in 27 carriers of XLRP and described 4 grades of fundus findings from grade 0 (normal) to grade 3 (diffuse changes). They found that carriers of XLRP with only a tapetal-like retinal reflex (grade 1) at presentation were more likely to retain visual function than those with peripheral retinal pigmentation. Grover et al. (2000) concluded that these data are useful in counseling such carriers as to their visual prognosis. In a study of 242 female carriers of X-linked RP, half of whom had RP2 or RP3, Comander et al. (2015) found that most carriers had mildly or moderately reduced visual function but rarely became legally blind. In most cases, obligate carriers could be identified by ERG testing. XLRP carrier ERG amplitudes and decay rates over time were on average half of those of affected men, consistent with the Lyon hypothesis of random X inactivation. Grover et al. (2002) compared the extent of intraocular light scatter (straylight) in carriers of choroideremia (CHM; 303100) and the various forms of XLRP to clarify the relationship between photoreceptor cell degeneration and intraocular light scatter in hereditary retinal degenerations. The carriers of XLRP who had evidence of photoreceptor cell dysfunction (as determined by visual field loss and reduced electroretinogram amplitudes) had increased levels of intraocular straylight, whereas the carriers of CHM, who showed fundus abnormalities alone, in the absence of demonstrable photoreceptor cell dysfunction, had normal or minimally elevated levels of light scatter. The authors concluded that the clinical symptom of glare, often reported by patients with RP, results, at least in part, from increased intraocular straylight caused by alterations in the optical quality of the crystalline lens as a consequence of photoreceptor cell degeneration. Mapping That the entity in the family reported by Hoare (1965) was identical to (or allelic with) that discussed in this entry was established by demonstration of identical linkage relationships (Bhattacharya et al., 1985; Jay, 1987). In linkage studies with the L1.28 probe (DXS7), Bhattacharya et al. (1984) found a maximum lod score of 7.89 at a distance of 3 cM (95% confidence limits 0-15). Friedrich et al. (1985) also published data on linkage with L1.28 (DXS7) and C-banding heteromorphism. They concluded that the RP2 locus is close to the centromere. RP2 lies between the centromere and DXS7. The same group used centromeric heteromorphism to place Menkes disease (309400) close to the centromere. Clayton et al. (1986) summarized the data to that time on linkage to DXS7. A maximum lod score of 14.01 at a theta of 0.08 was obtained. There was no evidence for heterogeneity of recombination fraction among the 13 families for which data were available. Wright et al. (1987) analyzed linkage against Xp markers. The portion of the chromosome distal to OTC was excluded as the location of RP2. The linkage observed with OTC was theta = 0.19 (lod = 3.61). The most closely linked DNA marker was DXS7 (theta = 0.09; lod = 8.66). Chen et al. (1987) found a more distal location of the RP locus in 3 large pedigrees which may have represented a separate disorder; heterozygotes showed the characteristic tapetal reflex. In this family, OTC and RP2 seemed to be tightly linked (lod = 10.64; theta = 0.00). It was presumably RP3 (300029) that Chen et al. (1987) were dealing with in this family. Litt et al. (1987) found no recombination of RP2 with DXS7 or with DXZ1, a centromeric site detected by an alpha-satellite probe. On the basis of a study of 20 kindreds, Wright et al. (1987) concluded that X-linked RP lies proximal to DXS7, which has been mapped to Xp11.3. Meitinger et al. (1989) demonstrated linkage to an informative hypervariable marker defining the DXS255 segment; theta = 0.07 at a maximum lod of 4.75. Farrar et al. (1988) contributed linkage data to the question of heterogeneity in X-linked RP. Chen et al. (1989) presented further data supporting the existence of 2 separate RP loci on Xp; by multipoint linkage analysis with 10 loci in 9 affected families, the mutation mapped telomeric to DXS7 in 7 and centromeric to DXS7 in 2. Microsatellites are stretches of tandemly repeated dinucleotides, such as poly(dGdT).(dCdA), which are widely distributed throughout eukaryotic genomes. Many microsatellites are hypervariable by reason of a variable number of dinucleotide repeats. Such polymorphisms can be studied by using PCR to amplify across the repeats and then resolving size differences (multiples of dinucleotides) in the PCR product by PAGE (Litt and Luty, 1989; Weber and May, 1989). Coleman et al. (1990) found that one such polymorphic microsatellite, DXS426, maps to Xp11.4-p11.22. They used this information for refinement of the location of the RP2 gene, which they concluded lies between DXS426 and DXS7. Wright et al. (1991) found no recombination with DXS255 (in Xp11.22) or TIMP (in Xp11.3-p11.23; 305370). Friedrich et al. (1992) used DNA markers and the cytogenetic centromere marker for linkage mapping in a large Danish family. They found the highest location score for a site distal to DXS255 and proximal to the OTC locus. In comparison with the first large Danish family that Friedrich et al. (1985) had studied, the recombination fraction between the centromere and the proximal genetic marker on the short arm, DXS7, was 0.17, which corresponded to the distance 18 cM recorded by HGM10 (Keats et al., 1989). However, in the second Danish family (Friedrich et al., 1992), the pericentric recombination fraction was increased, leading them to speculate that the difference in the size and location of the centromeric heterochromatin was responsible. Involvement of centromeric heterochromatin in recombination is well known in Drosophila; recombination in the euchromatin near the centromere is usually reduced, the so-called centromere effect. Variability in the position and amount of heterochromatin was observed between the 2 families. Another finding of note in the second family was the presence of several blind female carriers and a few female carriers with no phenotypic signs on thorough ophthalmologic examination and full field electroretinography (Friedrich et al., 1992). Thiselton et al. (1996) reported a defined localization for the RP2 gene to a 5-cM interval in Xp11.3-p11.23. Cytogenetics In 2 unrelated families in which males were affected with retinal dystrophy but had normal intellectual development, Delphin et al. (2012) performed linkage analysis followed by high-resolution oligonucleotide microarray and defined deletions on chromosome Xp11.3 in each family. In the first family, a 509-kb deletion encompassed the 3-prime end of the ZNF673 gene (300585) and the 5-prime half of the PHF16 gene (300618). The proband in the second family carried 2 neighboring 431-kb and 388-kb deletions; the centromeric deletion encompassed the 3-prime UTR of ZNF673 and intron 4 of RP2, whereas the telomeric deletion encompassed no known gene. Patients in the first family showed very similar age and mode of onset of the disease, exhibiting early severe myopia and macular rearrangements with preservation of the peripheral retina, but flat electroretinographic (ERG) responses before the age of 6 years. The proband in the second family presented at age 4 with jerk nystagmus, high bilateral myopia, diffuse retinal pigment epithelium (RPE) atrophy, and normal ERG recordings. By age 8, examination showed bull's eye macula with peripapillary atrophy, peripheral atrophic RPE with some pigmentary deposits and thin retinal vessels, central scotoma and constricted peripheral visual field, and severely altered photopic and scotopic ERG responses. Molecular Genetics In 6 patients with X-linked retinitis pigmentosa, Schwahn et al. (1998) detected 6 different mutations in a novel gene (RP2; 300757). In a cohort of North American families with X-linked retinitis pigmentosa, Mears et al. (1999) reported 5 protein truncation mutations of the RP2 gene. These were different from the 7 reported in European families by Schwahn et al. (1998), suggesting a high rate of new mutations and a lack of founder effect. Chapple et al. (2000) identified putative sites for N-terminal acyl modification by myristoylation and palmitoylation in the RP2 protein, consistent with its primary localization in the plasma membrane in cultured cells. Mutations in residues potentially required for N-terminal acylation revealed that the palmitoyl moiety is responsible for targeting of the myristoylated protein from intracellular membranes to the plasma membrane. The ser6del mutation (300757.0001) interfered with targeting of the protein to the plasma membrane, suggesting to the authors that the ser6del mutation may cause XLRP because it prevents normal amounts of RP2 from reaching the correct cellular locale. The R118H mutation (300757.0003) did not have a similar effect on localization. Miano et al. (2001) identified 5 novel mutations in RP2, each in a different XLRP family. These mutations included 3 missense mutations, a splice site mutation, and a single base insertion, which, because of a frameshift, led to a premature stop codon. Grayson et al. (2002) examined the relationship between RP2, cofactor C (602971), and ARL3 (604695) in patient-derived cell lines and in the retina. Examination of lymphoblastoid cells from patients with the arg120-to-ter mutation in RP2 (R120X; 300757.0008) revealed that the expression levels of cofactor C and ARL3 were not affected by the absence of RP2. Biochemical Features Using the highly informative probe M27-beta that detects the DXS255 locus, which is differentially methylated on the active and inactive X chromosomes, Friedrich et al. (1993) determined the methylation status of the RP2 gene in 7 obligate carrier females and 6 daughters of obligate carriers, all from the same family, whose linkage relationships suggested that they carried the RP2 gene. In 5 blind heterozygotes (aged 43 to 68 years), they found that the X chromosome carrying the RP2 gene was methylated and active in nearly all cells. The opposite X-inactivation pattern was found in a carrier female, aged 45 years, who gave normal findings on eye examination. Carriers with less skewed X inactivation had a less severe clinical outcome. However, Friedrich et al. (1993) found little or no correlation between phenotypes and the methylation status of the X chromosomes. Pathogenesis By searching protein sequence databases, Schwahn et al. (2001) determined that RP2 and cofactor C represent members of 2 distinct orthologous groups. All previously identified missense mutations in RP2 affected amino acid residues which are conserved in all RP2 orthologs or both orthologous groups. Studies of RP2-green fluorescent protein fusion proteins in transiently transfected cells showed that a mutation in the N terminus of RP2 abolished localization to the plasma membrane, whereas C-terminal protein truncation mutations led to scattered fluorescent foci in the cytoplasm. Western blot analysis failed to detect RP2 protein in immortalized cell lines from patients with protein truncation mutations, while mRNA was still present. The authors concluded that loss of RP2 protein and/or aberrant intracellular distribution might be the basis for the photoreceptor cell degeneration in most RP2 cases. Heterogeneity Teague et al. (1994) analyzed 40 kindreds with X-linked retinitis pigmentosa for linkage heterogeneity, concluding that 56% were of the RP3 type and 26% of the RP2 type. Bayesian probabilities of linkage to RP2, RP3, or to neither locus were calculated. This showed that 20 of 40 kindreds could be assigned to one or the other locus, with a probability of more than 0.70 (14 RP3 kindreds and 6 RP2 kindreds). A further 3 kindreds were found to be unlinked to either locus, with a probability of more than 0.8. The remaining 17 kindreds could not be classified unambiguously. This highlighted the difficulty of classifying families in the presence of genetic heterogeneity, where the 2 loci are separated by an estimated 16 cM. Aldred et al. (1994) described RP2 and RP3 regions of Xp. In one case, reassessment of the family in light of these results suggested that the affected individuals may, in fact, have an autosomal dominant form of RP. The remaining 2 families were consistent with X linkage and suggested the possibility of a new X-linked RP locus. Miano et al. (2001) stated that as many as 5 distinct loci on the X chromosome determine X-linked retinitis pigmentosa, but only 2 XLRP genes had been identified: RPGR (312610) and RP2. Mutations in these genes account for approximately 70% and 10% of XLRP patients, respectively. Clinically, there are no clearly significant differences between RP3 and RP2 phenotypes. Sharon et al. (2003) screened 187 unrelated male patients for mutations in the RP2 and RPGR genes, including 135 with a prior clinical diagnosis of XLRP, 11 with probable XLRP, 30 isolated cases suspected of having XLRP, and 11 with cone-rod degeneration. Among the 187 patients, they found 10 mutations in RP2, 2 of which were novel, and 80 mutations in RPGR, 41 of which were novel; 66% of the RPGR mutations were within ORF15. Among the 135 with a prior clinical diagnosis of XLRP, mutations in the RP2 and RPGR genes were found in 9 of 135 (6.7%) and 98 of 135 (72.6%), respectively, for a total of 79% of patients. Patients with RP2 mutations had, on average, lower visual acuity but similar visual field area, final dark-adapted threshold, and 30-Hz ERG amplitude compared with those with RPGR mutations. Pelletier et al. (2007) reported the screening of the RP2 and RPGR genes in a cohort of 127 French families comprising 93 familial cases of retinitis pigmentosa suggesting X-linked inheritance, including 48 of 93 families; 7 male sibships of RP; 25 sporadic male cases of RP; and 2 cone dystrophies (COD). They identified a total of 14 RP2 mutations, 12 of which were novel, in 14 of 88 familial cases of RP and 1 of 25 sporadic male cases (4%). In 13 of 14 of the familial cases, no expression of the disease was noted in females, while in 1 of 14 families 1 woman developed retinitis pigmentosa in the third decade. A total of 42 RPGR mutations, 26 of which were novel, were identified in 80 families, including 69 of 88 familial cases (78.4%); 2 of 7 male sibship cases (28.6%); 8 of 25 sporadic male cases (32%); and 1 of 2 COD. No expression of the disease was noted in females in 41 of 69 familial cases (59.4%), while at least 1 severely affected woman was recognized in 28 of 69 families (40.6%). The frequency of RP2 and RPGR mutations in familial cases of retinitis pigmentosa suggestive of X-linked transmission was in accordance with that reported elsewhere (RP2: 15.9% vs 6-20%; RPGR: 78.4% vs 55-90%). About 30% of male sporadic cases and 30% of male sibships of RP carried RP2 or RPGR mutations, confirming the pertinence of the genetic screening of XLRP genes in male patients affected with RP commencing in the first decade and leading to profound visual impairment before the age of 30 years. History Spence et al. (1974) analyzed a large pedigree in which some heterozygous females had full-blown RP, making it difficult to distinguish X-linked from autosomal dominant inheritance with reduced penetrance. A computerized analysis indicated that the X-linked model is more than 1,000 times more likely than the autosomal model. Gieser et al. (1980) suggested that vitreous fluorophotometry may be a sensitive method for detecting heterozygous females. Grutzner et al. (1972) concluded that the loci for RP, for Xg blood group, and for color vision are widely separated on the X chromosome. Animal Model Acland et al. (1994) described an X-linked retinal degeneration in the Siberian Husky dog that they suggested might be a homolog of RP2 or one of the other forms of X-linked retinitis pigmentosa. INHERITANCE \- X-linked HEAD & NECK Eyes \- Retinitis pigmentosa \- Choroidoretinal degeneration \- Pigmentary retinopathy \- Gyrate choroidal atrophy \- Constricted visual fields \- Night blindness \- Cataract \- Early myopia MISCELLANEOUS \- Some heterozygous females show a blue-yellow color defect MOLECULAR BASIS \- Caused by mutation in the RP2 gene (RP2, 312600.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	RETINITIS PIGMENTOSA 2	c0035334	25,677	omim	https://www.omim.org/entry/312600	2019-09-22T16:17:19	{"doid": ["0110415"], "mesh": ["D012174"], "omim": ["312600"], "orphanet": ["791"], "genereviews": ["NBK1417"]}
A number sign (#) is used with this entry because angioid streaks, in addition to being a hallmark of pseudoxanthoma elasticum (PXE; 264800), occur in other settings. As the designation indicates, angioid streaks are vessel-like streaks in the ocular fundus. They have been shown to be due to cracking (crazing) in the Bruch membrane behind the retina. At least 50% of patients with angioid streaks have other evidence of pseudoxanthoma elasticum (in the skin and arteries, for example). Progression of the eye involvement with retinal hemorrhages can lead to blindness (Paton, 1972). Clarkson and Altman (1982) listed 14 systemic disorders associated with angioid streaks. The conditions most often associated with angioid streaks are Paget disease of bone (see 167250) and sickle cell anemia (603903) (Geeraets and Guerry, 1960) and thalassemia (see 141900) (Aessopos et al., 1989). Other frequently associated disorders include tumoral calcinosis with hyperphosphatemia (211900), hemochromatosis (235200), and lead poisoning. Green et al. (1966) found typical angioid streaks in 2 of 6 affected members of a kindred with Ehlers-Danlos syndrome (see 130000). Although the diagnosis of both angioid streaks and Ehlers-Danlos syndrome seems unequivocal, the association may have been coincidental because the association has not been described by others (McKusick, 2002). Gorin et al. (1994) described a 32-year-old Jewish male and a 36-year-old Japanese female who had abetalipoproteinemia (200100) associated with angioid streaks. The association had previously been noted by Muller and Lloyd (1982) and Dieckert et al. (1989). Gorin et al. (1994) suggested that a common metabolic pathway involving trace element deficiencies may account for the association with abetalipoproteinemia and certain other rare disorders. Choroidal neovascularization is the major cause of vision loss associated with angioid streaks. The pathogenesis of choroidal neovascularization associated with angioid streaks is believed to be related to cracks in the Bruch membrane, which allow new vessels to invade the subretinal space. Karacorlu et al. (2002) found that photodynamic therapy using verteporfin generally achieved short-term cessation of or decrease of fluorescein leakage from subfoveal choroidal neovascularization without loss of vision in patients with angioid streaks. No photodynamic therapy-related ocular complications were reported in any case in this study. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	ANGIOID STREAKS	c0002982	25,678	omim	https://www.omim.org/entry/607140	2019-09-22T16:09:35	{"mesh": ["D000793"], "omim": ["607140"]}
Progestogen hypersensitivity causes a skin reaction that typically occurs during a woman's menstrual cycle. Symptoms usually begin 3-10 days before a woman's period and go away when her period is over. Skin symptoms may include rash, swelling, itching, hives, and red, flaky patches. More severe symptoms can include open sores, wheezing, and an asthma-like reaction. Progestogen hypersensitivity symptoms stop at the time of menopause. The exact cause of progestogen hypersensitivity is unknown, but many women with this condition have had exposure to external sources of progesterone such as oral contraceptives or drugs used for fertility treatments. Some women develop progestogen hypersensitivity in response to the progesterone naturally produced by the body. Diagnosis is based on the symptoms, clinical exam, and a skin test. Treatment is focused on managing the symptoms and may include medications that block the activity of progesterone or stop the body from making progesterone. Progesterone desensitization and surgery to remove the ovaries may cure the symptoms of progestogen hypersensitivity. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Progestogen hypersensitivity	c1260879	25,679	gard	https://rarediseases.info.nih.gov/diseases/9139/progestogen-hypersensitivity	2021-01-18T17:58:09	{"mesh": ["C535299"], "umls": ["C1260879"], "synonyms": ["APD", "autoimmune progesterone dermatitis"]}
A rare, acquired, dermis elastic tissue disorder with decreased elastic tissue characterized by multiple, asymptomatic, well demarcated, flat, hypopigmented atrophic macular skin lesions distributed over upper trunk and proximal upper limbs. Histopathological examination reveals atrophic epidermis with decreased basal pigmentation, perivascular mononuclear infiltration in the upper dermis, and disorganized, hyalinized, coarse collagen bundles, and variable loss of elastic fibers in the dermis. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Confetti-like macular atrophy	None	25,680	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=221142	2021-01-23T17:12:19	{"icd-10": ["L90.8"]}
Sinus bradycardia is a sinus rhythm with a rate that is lower than normal This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Sinus bradycardia" – news · newspapers · books · scholar · JSTOR (August 2014) (Learn how and when to remove this template message) Sinus bradycardia ECG of Sinus bradycardia with a heart rate of 43 bpm. SpecialtyCardiology Symptoms * lightheadedness * dizziness * hypotension * vertigo * syncope Diagnostic methodelectrocardiogram Sinus bradycardia is a sinus node dysfunction with a rate that is lower than normal. In humans, bradycardia is generally defined to be a rate of under 60 beats per minute.[1] A normal heartbeat in human is usually at a rate of 60 to 100 beats per minute.[2] ## Contents * 1 Signs and symptoms * 2 Pathophysiology & etiology * 3 Diagnosis * 4 See also * 5 References * 6 External links ## Signs and symptoms[edit] The decreased heart rate can cause a decreased cardiac output resulting in symptoms such as lightheadedness, dizziness, hypotension, vertigo, and syncope. The slow heart rate may also lead to atrial, junctional, or ventricular ectopic rhythms. Bradycardia is not necessarily problematic. People who regularly practice sports may have sinus bradycardia, because their trained hearts can pump enough blood in each contraction to allow a low resting heart rate. Sinus bradycardia can also be an adaptive advantage; for example, diving seals may have a heart rate as low as 12 beats per minute, helping them to conserve oxygen during long dives.[3] Sinus bradycardia is a common condition found in both healthy individuals and those who are considered well conditioned athletes.[4] Heart rates considered bradycardic vary by species; for example, in the common housecat, a rate of under 120 beats per minute is abnormal. Generally, smaller species have higher heart rates while larger species have lower rates.[5] ## Pathophysiology & etiology[edit] Rhythm strip of sinus bradycardia at 50 bpm * Sinus bradycardia is commonly seen in normal healthy persons and athletes in the absence of pathophysiological diseases or conditions.[1] * Different factors or etiologies could lead to the dysfunction of the sinus node, causing a malformation or prolongation of the impulse. * In terms of pathophysiological diseases, sinus rhythm may be caused by: * Diseases/Conditions: * Acute myocardial infarction, carotid sinus syndrome, eating disorders (such as anorexia nervosa) rhodotoxin poisoning, hypothermia, hypothyroidism, infections (such as diphtheria, acute rheumatic fever, or viral myocarditis), intrinsic disease of the SA node (such as sick sinus syndrome), Roemheld syndrome, sleep apnea * Physiological causes: * Increased vagal tone, increased intracranial pressure * Medications, most commonly: digitalis glycosides, beta-blockers, quinidine, adenosine, calcium channel blockers, class I antiarrhythmic agents, ivabradine, clonidine, reserpine, cimetidine, lithium, amitriptyline ## Diagnosis[edit] Diagnosis of sinus bradycardia can be confirmed by an electrocardiogram that shows the following characteristics:[1] * Rate: Less than 60 beats per minute. * Rhythm: Regular. * P waves: Upright, consistent, and normal in morphology and duration. * PR interval: Between 0.12 and 0.20 seconds in duration. * QRS complex: Less than 0.12 seconds in width, and consistent in morphology. Taking a thorough medical history and physical exam by healthcare providers can also help with narrowing differential diagnosis. Any recent changes to patient's medication history, new symptoms such as chest pain, shortness of breath and palpitations, family history of sinus bradycardia, physical exam that reveals cyanosis, peripheral edema, altered mental status, dyspnea, rales and crackles are all relevant information to consider for differential diagnosis.[1] ## See also[edit] * Sinus tachycardia * Long QT syndrome ## References[edit] 1. ^ a b c d Hafeez Y, Grossman SA (2020). "Sinus Bradycardia". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 29630253. Retrieved 2020-07-27. 2. ^ "Sinus Bradycardia". Cedars-Sinai. Retrieved 2020-07-28. 3. ^ Thornton SJ, Hochachka PW (2004). "Oxygen and the diving seal" (PDF). Undersea & Hyperbaric Medicine : Journal of the Undersea and Hyperbaric Medical Society, Inc. 31 (1): 81–95. PMID 15233163. 4. ^ Salyer SW (2007). "Chapter 2 - Cardiology". In Salyer SW (ed.). Essential emergency medicine: for the healthcare practitioner. Saunders/Elsevier. pp. 37–96. ISBN 978-1-4160-2971-7. 5. ^ Milani-Nejad N, Janssen PM (March 2014). "Small and large animal models in cardiac contraction research: advantages and disadvantages". Pharmacology & Therapeutics. 141 (3): 235–49. doi:10.1016/j.pharmthera.2013.10.007. PMC 3947198. PMID 24140081. ## External links[edit] Classification D * ICD-10: R00.1 * ICD-9-CM: 427.81 * MeSH: D001146 * 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-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Sinus bradycardia	c0085610	25,681	wikipedia	https://en.wikipedia.org/wiki/Sinus_bradycardia	2021-01-18T19:04:33	{"umls": ["C0085610"], "icd-9": ["427.89"], "icd-10": ["R00.1"], "wikidata": ["Q2995544"]}
Part of a series on Doping in sport Substances and types * Anabolic steroids * Blood doping * Gene doping * Cannabinoids * Diuretics * Painkillers * Sedatives * Stem cell doping * Stimulants * Beta2-adrenergic agonist * Clenbuterol * Ephedrine * EPO * Human growth hormone * Methylhexanamine * SARMs * Stanozolol * Tetrahydrogestrinone Terminology * Abortion doping * Biological passport * Blood-spinning * Doping test * Performance-enhancing drugs * Repoxygen * Stem cell doping * Whizzinator History * Olympics * Tour de France (1998, 1999, 2007) * Auto racing * BALCO scandal * Clemson University steroid scandal * U of South Carolina steroid scandal * Dubin Inquiry * Association Football * China * East Germany * Russia * United States * Festina affair * Floyd Landis case * Game of Shadows * Juiced * L.A. Confidentiel * Lance Armstrong * History of allegations * Doping case * Operación Puerto * Operation Aderlass * Doping in American football * Steroid use in baseball * Barry Bonds perjury case * Mitchell Report * Biogenesis scandal Doping-related lists * Doping cases in Sport * Athletics * Cycling * Doping at the Olympic Games * Doping at the World Championships in Athletics * Stripped Olympic medals * Stripped European Athletics C'ships medals * Drugs banned from the Olympics * MLB players suspended for doping * MLB players in the Mitchell Report Anti-doping bodies * World Anti-Doping Agency * International Testing Agency * List of national anti-doping organizations * Australian Sports Anti-Doping Authority * French Anti-Doping Agency * National Anti-Doping Agency * Russian Anti-Doping Agency * UK Anti-Doping * United States Anti-Doping Agency * v * t * e Alexander Vinokourov, pictured in 2006, tested positive for doping during the 2007 Tour. The 2007 Tour de France was affected by a series of scandals and speculations related to doping.[1] By the end of the Tour, two cyclists were dismissed for failing tests and the wearer of the yellow jersey was voluntarily retired by his team for lying about his whereabouts and missing doping tests. A fourth rider was confirmed to having used doping while in a training session prior to the 2007 Tour and a fifth rider failed tests late in the race, with his result being officially announced just after the end of the Tour. During the competition, two teams were asked to withdraw after at least one member was found to have doped. The events generated criticism and a general distrustful attitude toward the sport of professional cycling from media and public opinion. The doping allegations also resulted in several team sponsors threatening to retire their support if events advanced further. Some media such as German TV channels ARD and ZDF left the Tour once the first scandals broke. Following the Tour's conclusion, the sport's governing bodies spoke out about ways to combat the prevalence of doping in cycling and key team sponsors elected to withdraw their support due to the reputational damage caused by the scandals. The 2007 Tour de France has been referred to as one of the most controversial Tours.[2] After the end of the Tour, The Times of London ranked it 4th in its list of the top 50 sporting scandals.[3] ## Contents * 1 Background * 2 Events immediately before the Tour * 3 During the Tour * 4 Reaction to events during the Tour * 5 Riders who failed tests * 5.1 Patrik Sinkewitz * 5.2 Alexander Vinokourov * 5.3 Cristian Moreni * 5.4 Iban Mayo * 6 Other affected riders * 6.1 Michael Rasmussen * 6.2 Alberto Contador * 7 Other developments * 8 See also * 9 References ## Background[edit] Floyd Landis on the 2006 Tour de France Since the introduction of doping tests in 1964, many cyclists were caught in the Tour de France. In recent years, 1996 Tour de France winner Bjarne Riis and points classification winner Erik Zabel, along with most of their Team Telekom team-mates, confessed to using erythropoietin (EPO).[4][5][6] In 1997, former points classification winner Djamolidine Abdoujaparov was disqualified from the Tour de France for doping use.[7] In 1998, the Festina affair had several main contenders removed from the race. In the next years, several riders were removed from the Tour de France for doping (see List of doping cases in cycling). In addition, several riders were not allowed to start the previous Tour, including Jan Ullrich and Ivan Basso because of their involvement in the Operación Puerto doping case, a Spanish investigation against doctor Eufemiano Fuentes and a number of accomplices accused of administering prohibited doping products to approximately two hundred professional athletes, to enhance their performance. After the completion of the 2006 Tour, winner Floyd Landis was found to have an elevated testosterone to epitestosterone ratio on a sample taken following Stage 17 of the race, and at the time of the 2007 Tour prologue. Since the results of an independent arbitration hearing were still pending Landis was prevented from defending his title. He was stripped of his 2006 Tour title in September 2007. ## Events immediately before the Tour[edit] Alessandro Petacchi Alessandro Petacchi, a sprint specialist, failed a test for salbutamol at Pinerolo on 23 May in the 2007 Giro d'Italia, the same day he claimed the third of his five-stage wins in the event. As a result, Petacchi, an asthma sufferer, was suspended by Team Milram and forced to miss the Tour de France because of the charges.[8] Though he seemed cleared of the charges at one point,[9] he was later suspended for one year.[10] On May 25, Bjarne Riis admitted he had won the overall competition of the 1996 edition under the effects of performance-enhancing drugs, claiming "for a time [doping] was a part of everyday life for me", and he was later stripped of the title. Five other former Telekom teammates were also implicated in doping.[6] On May 24, riders Erik Zabel and Rolf Aldag had earlier admitted to using banned blood booster EPO in the mid-1990s. Other high-profile potential Tour riders were caught up in doping controversies. Giro d'Italia winner Danilo di Luca remained under investigation and 2006 Giro winner Ivan Basso was banned for two years on 15 June for his part in events uncovered by Operación Puerto.[6] ## During the Tour[edit] Despite Petacchi's failed test result prior to the Tour prologue, the first stages were uneventful in terms of doping allegations. It was not until Stage 8 before the first doping allegations surfaced against one of the participants. German cyclist Patrik Sinkewitz failed tests for elevated levels of testosterone at a June 8, 2007 pre-Tour training camp.[11] Immediately prior to Stage 12, reports began to surface that the then current race leader, Michael Rasmussen had been dropped by the Danish Cycling Union in the month prior to the Tour following claims he had missed three out-of-competition doping tests. Tour director Christian Prudhomme nevertheless allowed the rider to continue in the absence of a failed test result.[12] Days later on 24 July, pre-race favourite Alexander Vinokourov was withdrawn from the Tour after Stage 15. Vinokourov had returned a failed A test for an illegal blood transfusion from a compatible donor before the Stage 13 individual time trial on July 21, in which he placed first.[13] In addition to Vinokourov, who was in 23rd place overall, the entire Astana Team was forced to withdraw, affecting highly placed riders such as 5th placed Andreas Klöden and 8th placed Andrey Kashechkin. The following day, after finishing Stage 16, which had begun with a protest by riders, it emerged that Italian cyclist Cristian Moreni had failed tests for testosterone after Stage 11, in which he finished 102nd. He was immediately pulled out of the race by his team, Cofidis (who had participated in the day's protest). Team Cofidis then voluntarily retired the rest of their riders from the Tour.[14] Michael Rasmussen On 25 July Michael Rasmussen won Stage 16; with a three-minute lead, he appeared all but certain to win the Tour the next day. However, hours after his victory, Rasmssen's team, Rabobank, abruptly pulled Rasmussen from the Tour and sacked him for a violation of the team's internal rules. The Danish rider had given incorrect information to Rabobank's sports director about his whereabouts which followed on from earlier reports that he had missed previous out-of-competition doping control tests.[15] With the sport reeling from the revelations, the Tour continued as allegations began to surface regarding new race leader Alberto Contador (see Alberto Contador below). While no further rider or team withdrawals occurred before the race's conclusion in Paris, it later emerged that two more riders Andrey Kashechkin and Iban Mayo had failed tests for doping during the Tour's later stages. ## Reaction to events during the Tour[edit] Prior to Rasmussen's exit, the doping revelations of Sinkewitz and Vinokourov had been met with defiance by the UCI, the Tour organizers and the majority of the European press (with certain exceptions) however, with Rasmussen's sacking whilst wearing the yellow jersey (no rider had previously been withdrawn from the race while leading), the mood became more pessimistic, with the exception of Tour director Christian Prudhomme who publicly regarded the Dane's withdrawal as "the best thing that can happen to the Tour. The race will go on for the rest of the riders and we believe it would be an insult to them to stop the race. We believe the general classification is much better now than it was."[16] Prudhomme's reaction was in contrast to the French newspapers. France Soir ran a mock death notice declaring the Tour had died "at age 104, after a long illness." Declaring further: "The Tour is clinically dead. It is a broken toy, a burst soap bubble popped by careless kids, unaware that they are damaging themselves, their health and their childhood dreams as well...It's all the more painful as we had almost begun to believe in the Tour again... in these soap-and-water cyclists who we were so ready to love. But instead of dreams, the last 48 hours have been a living nightmare." A similar editorial in Le Figaro announced: "It really doesn't matter who wins the Tour. The 2007 edition died on 24 July on the heights of Loudenvielle...Killed by Alexander Vinokourov, idolised by the media and cycling fans, but revealed to have the blood of another running in his veins on the finishing line. Damn Vinokourov! He sullied the infinite beauty of the Pyrenees, dirtied cycling a little more and further discredited the Tour de France." Another French newspaper, Libération's editorial demanded "The Tour must be stopped", describing the procession of cyclists as a "caravan of ridicule".[17] The British popular media who had previously acclaimed the success of the Tour's prologue in London and the first stage through Kent,[18] were similarly critical calling it the Tour de Farce (Daily Mirror) and declaring it a "Corrupt race populated by a cast of frauds heading straight into the gutter" (The Times). Swiss newspaper Tages-Anzeiger reduced its coverage of the race in protest to minimal reporting of results and full reporting of any doping stories.[17] German television broadcasters ARD and ZDF stopped covering the race (after they vowed to in the Tour prelude) when Patrik Sinkewitz was revealed to have failed tests following Stage 8; Sat 1 and Pro Sieben replaced them as the German rightsholders.[19] Most other media decided to stay, and some even criticised the German decision. Sponsors similarly indicated their unwillingness to continue to support a sport dogged by scandal, most noticeably Gerolsteiner and T-Mobile (the latter subsequently withdrew from sponsoring cycling later in the year).[20] Team Rabobank's head of sponsorship Heleen Crielaard reacted to the Rasmussen dismissal stating: "We are a bank and we want to be reliable. One thing we definitely do not appreciate is lying..." although denied suggestions that they had influenced the decision to sack the rider.[16][21] Despite calls for the Tour to be cancelled mid-race,[17] the race continued principally on the basis that the race itself and its history is bigger than individual events.[22] UCI director Pat McQuaid urged team directors and the riders to take responsibility: > "The teams need to have more control over their riders.."They are the ones who need to clean out the riders who are iffy, they need to ensure they can guarantee that everyone of their riders is riding clean and riding fairly. The evidence is that most of the time these riders are dealing with individuals from outside their team and the sport whether it be pseudo doctors and chemists who are promising them things. That has got to stop. More and more riders...are speaking out and it's the younger generation of riders coming in that are going to be the future of the sport. They have to come into a system that is completely ethically correct. But at the end of the day, the rider is the one who makes the decisions..We are in the process of changing that culture and it will change in time. We need to weed out the bad apples. I hope next year we have a Tour de France with no positive tests. We've had two bad Tour de Frances, we cannot afford a third."[16] Eddy Merckx who had won the Tour on five occasions, commented: "my heart is no longer in it" in response to his support for the Tour. Another Belgian rider Johan Museeuw (who had previously received a two-year ban for doping), suggested doping and drug use were a possible consequence of the difficulty of riding the Tour in its current format. Questioning why stages had to be so long and including several arduous 'out-of-category' mountain climbs.[21] Following Vinokourov's exit, Patrice Clerc president of Tour organisers Amaury Sport Organisation (ASO) stated: "I am not downcast and I am all the more determined to go all the way in this fight...It may seem paradoxical but we are closing in on victory. I have been saying we have started a merciless war against doping...We live in dark times and it is out of the question to give up, it is out of the question to leave the place to those who cheat."[23] Particularly strong reaction came from Jean-Francois Lamour, vice president of the World Anti-Doping Agency who called for the Tour de France to be banned entirely and for road cycling to be withdrawn from the Olympic Games[17] and former British Olympic Association chairman Sir Craig Reedie suggested that road cyclists might be required to hold an "anti-doping passport". French Prime Minister François Fillon attempted to stem the tide of negativity stating: "Obviously this gives a disastrous image of the Tour de France, but at the same time, if we encourage the organisers, we can clean up French sports and in particular cycling";[17] whilst Nicolas Sarkozy, the French president, demonstrated support by joining the Tour and following the race leaders in the Tour director's car. Prior to Stage 16 a group of riders from eight teams - six from France plus German outfits Team Gerolsteiner and T-Mobile Team \- forming the Mouvement pour un cyclisme crédible (or Movement for Credible Cycling), delayed the start of the Tour by thirteen minutes asking for all teams to abide by their good behaviour charter of 2005, under which teams are requested to avoid fielding riders implicated in doping affairs.[6] The protest was in obvious contrast to the 1998 reaction which was at odds with authorities, protesting at the heavy-handed treatment of riders. Tour riders generally remained encouraged however. Fabian Cancellara, Cedric Vasseur and David Millar all stated publicly that they believed the consensus among riders in the peloton was that anti-doping measures were effective and the sport would continue to benefit from the harder line.[16][21] ## Riders who failed tests[edit] ### Patrik Sinkewitz[edit] Patrik Sinkewitz at the Henninger Turm 2006 Despite the rider's failed test result relating to a pre-Tour training camp, Sinkewitz competed in the race until Stage 8, when he collided with a spectator and withdrew from the event, at which point the test result emerged. Sinkewitz initially denied the allegation and called for his B sample to be tested. German television withdrew from covering the Tour in protest when his failed test came to light.[19] On 31 July Sinkewitz subsequently retracted his denial and confessed to using a testosterone gel on his upper arms whilst training. Accepting the failed test result, Sinkewitz stated that: "It was a big mistake and irresponsible toward my team, colleagues, the sponsor and the whole of cycling."[24] T-Mobile responded to the admission by sacking Sinkewitz with immediate effect.[24] ### Alexander Vinokourov[edit] Alexander Vinokourov began the Tour as one of the favourites.[25] Vinokourov's A test revealed two different types of red blood cells in his circulatory system indicating he had a blood transfusion prior to the stage. A blood transfusion is meant to increase the number of red blood cells in the body, improving oxygen flow from the lungs to the muscles.[25] Vinokourov rejected the failed test, blaming the anomaly on excessive blood flow in his thighs following a heavy collision earlier in the Tour.[25] Accordingly, he asked for his B sample to be tested; however, the lab test for locating blood cells from another donor in "old fashioned" homologous transfusions is considered fool-proof.[26] It was later revealed that he had also failed tests on his win of stage 15, and that his B sample had since returned "non-negative".[27] Astana responded by sacking Vinokourov.[28] ### Cristian Moreni[edit] Cristian Moreni Cofidis rider Moreni was placed 54th at the time he was withdrawn from the Tour and had participated in the rider protest prior to Stage 16. His failed test related to Stage 11 and Moreni decided not to ask for his B sample to be tested, admitting to doping according to Cofidis team manager Eric Boyer.[29] ### Iban Mayo[edit] Spanish cyclist Iban Mayo was tested for doping on the second rest day, on July 24. The test failed for EPO after the Tour's conclusion. He was subsequently suspended by his team Saunier Duval-Prodir.[30] Mayo had previously failed tests for a high testosterone-to-epitestosterone ratio during the 2007 Giro d'Italia,[31] but on that occasion UCI found that he had not breached any doping regulation.[32] Mayo placed 16th overall in the 2007 Tour. It later emerged in October 2007 that Mayo's B-sample would be re-tested after results from a laboratory in Ghent returned inconclusive results.[33] ## Other affected riders[edit] ### Michael Rasmussen[edit] Despite being tested negative for doping before the Tour and seventeen times during the Tour, Michael Rasmussen was pulled from the race for violating team rules. According to Rabobank, he had told the UCI and the team that he was training in Mexico from June 4 to June 26, 2007. Italian cycling journalist and former cyclist Davide Cassani told a Danish television channel that he had seen Rasmussen on June 13 and 14 in the Dolomites in Italy.[34] When Rabobank team director Theo de Rooij confronted Rasmussen with this story, according to news reports he allegedly admitted the lie.[35] Rasmussen denied admitting this, however and told a Dutch newspaper (Algemeen Dagblad) "My career is ruined".[21][36][37] According to Team Rabobank spokesman Jacob Bergsma, when sponsor Rabobank learned of Rasmussen's deceit, they insisted that he be sent home immediately.[38] Rasmussen had previously been given two warnings from UCI and two warnings from Anti Doping Denmark for missing out-of-competition doping controls. Three warnings from either organization would have landed him with a ban. The warnings had no immediate consequences, but cast a cloud of doubt about whether Rasmussen was doping.[12] Michael Rasmussen's withdrawal came immediately after his dramatic victory in Stage 16, defending multiple attacks from Alberto Contador on a gruelling mountain pass. At the time he was holding the yellow jersey, leading the race by three minutes and ten seconds, and he appeared well on his way to winning the Tour.[39] Over three months later on 8 November, Danish newspapers reported that Rasmussen had admitted misleading the UCI as to his whereabouts, an offence that carries a penalty of two years suspension.[40] ### Alberto Contador[edit] Alberto Contador was not allowed to start in the 2006 Tour de France due to his possible involvement with the Operación Puerto doping case in which he had been referred to by key persons who were the subject of investigation. He was subsequently cleared and allowed to start in 2007, going on to win the Tour. Contador signed a commitment in which he stated: "I am not involved in the Puerto affair nor in any other doping case".[41] But according to documents obtained by the French newspaper Le Monde, he was still involved in the Puerto affair and therefore should not have been allowed to start the 2007 Tour.[42] Since Contador was the only rider able to stay with Rasmussen on two arduous stages in the Alps and Pyrenees, several journalists focused on his relationship with Eufemiano Fuentes and his role in Operación Puerto, without uncovering new evidence.[43][44] Contador was tested five times during the Tour, and no discrepancies were reported. After the Tour, German doping expert Werner Franke, who had complete access to Puerto documents, accused him of having taken drugs in the past.[45] On August 10, in response to increasing suspicion about links to the Operación Puerto blood-doping ring alleged by Franke, Alberto Contador publicly declared himself a clean rider: "I have never doped and I have never participated in an act of doping," said Contador, reading from a prepared statement. "I won the Tour clean. I cannot understand the attacks against by people that don't even know me. My commitment is absolute and I will always be ready to collaborate in the fight against doping." Contador was joined by Discovery Channel team manager Johan Bruyneel, Spanish sports minister Jaime Lissavetzky and members of his family.[46] Contador failed tests for clenbuterol in the 2010 Tour de France and was subsequently suspended from cycling for two years.[47] ## Other developments[edit] In addition to the sacking and resignations of a number of riders (see above) it was announced on 31 July that Team Astana had suspended team activities for one month, stating that: "Following recent events, we have decided to stop our activities until the end of August...This period of time will be the opportunity for deep questioning."[24] and two weeks after the Tour had finished it emerged that team-rider Andrej Kashechkin had also failed doping tests.[48] The Astana team were later banned from entering the next Grand Tour of the season, the 2007 Vuelta a España (or Tour of Spain) as a direct result of the failed doping tests of three of the team's riders.[49] On 3 August Team Rabobank's general director, Theo de Rooij announced his resignation from the team as a consequence of the events.[50] Both Michael Rasmussen and Alberto Contador were excluded from the Hamburg Cyclassics race later in the month after the Tour due to continuing allegations linking both riders to doping.[51] As well as the international media,[21] professional riders and sponsors,[52] a number of organisations involved with the Tour and professional cycling made statements about the future of the sport and the impact of doping.[53] The Discovery Channel Team subsequently announced they would be disbanding at the end of the 2007 season citing the "situation in the sport" at the time as one of the factors in their failure to find new sponsors.[54] Later in the year T-Mobile confirmed they would withdraw from sponsoring professional cycling in order to distance themselves from doping scandals which included Patrik Sinkewitz's failed test result in the 2007 Tour and previous admissions of doping by former T-Mobile team riders including Bjarne Riis.[55] In an interview broadcast in September 2007, president of the UCI Pat McQuaid referring to the Tour events, called for the then-current two-year ban for first-time doping offenders to be increased to a life ban in an effort to deter doping activity. The statement marked a shift in policy as the president had previously (during the Tour) expressed a belief that a two-year ban was sufficient.[56] On February 13, 2008, the ASO announced that the Astana team, despite completely changing its ownership, management, and rider roster since the 2007 scandals, would be barred from the 2008 Tour due to its involvement in the 2007 scandals and its links to Operación Puerto. The move meant that neither Contador, the 2007 winner, nor third-place Levi Leipheimer, both of whom signed with the revamped Astana setup, were able to compete in the 2008 tour.[57] ## See also[edit] Wikinews has News related to this article: * Tour de France: Alexander Vinokourov fails blood test * Tour de France: Yellow jersey Rasmussen withdrawn * Doping at the Tour de France * Doping (sport) * Blood doping * List of doping cases in cycling ## References[edit] 1. ^ "Doping incidents ahead of and during 2007 Tour de France". The Associated Press. 2007-07-28. Retrieved 2008-10-17. 2. ^ "Rasmussen Under Rabobank Investigation As Doping Scandal Rages On". eFluxMedia. 30 July 2007. Archived from the original on 23 June 2007. Retrieved 2008-10-17. 3. ^ Kidd, Patrick (22 August 2007). "The top 50 sporting scandals". The Times. London. Retrieved 2008-10-17. 4. ^ Westemeyer, Susan (2007-05-24). "Zabel and Aldag confess EPO usage". cyclingnews.com. Retrieved 2007-05-24. 5. ^ BBC Sports News, Zabel admits to doping at Telekom 6. ^ a b c d "Tour hit by fresh doping failure". BBC News. 2007-07-26. Retrieved 2007-07-26. 7. ^ Cycling News, July 1997, Uzbekistan's Djamolidine Abdoujaparov, expelled from the Tour de France for doping 8. ^ "Petacchi to miss Tour de France". BBC News. 2007-07-05. Retrieved 2007-07-26. 9. ^ "Petacchi cleared of doping charge". BBC News. 2007-07-05. Retrieved 2007-07-26. 10. ^ Charles Pelkey (May 7, 2008). "CAS suspends Petacchi". VeloNews. Competitor Group, Inc. 11. ^ Moulson, Geir (31 July 2007). "German Cyclist Admits Testosterone Use". Washington Post. Retrieved 24 November 2018. 12. ^ a b "Tour leader in drugs test dispute". BBC News. 2007-07-19. Retrieved 2007-09-04. 13. ^ Hiltzik, Michael (29 July 2007). "Vinokourov to fight doping charge". LA Times. Retrieved 24 November 2018. 14. ^ "Tour hit by fresh doping failure". BBC News. 2007-07-26. Retrieved 2007-07-26. 15. ^ "Leader Rasmussen Removed From Race". Washington Post. 25 July 2007. Retrieved 24 November 2018. 16. ^ a b c d "Rasmussen 'broken' by Tour exit". BBC News. 2007-07-26. Retrieved 2007-09-04. 17. ^ a b c d e Allen, Peter (2007-07-27). "Tour de France becomes drug-fuelled disgrace". The Daily Telegraph. London. Retrieved 2007-07-27. 18. ^ Trickett, Alex (2007-07-08). "McEwen wins Tour sprint thriller". BBC News. Retrieved 2007-09-04. 19. ^ a b "German TV suspends Tour coverage". BBC News. 2007-07-19. Retrieved 2007-07-31. 20. ^ Sage, Adam (2007-07-26). "France mourns 'death of the Tour' as sponsors get cold feet after scandal". The Times. London. Retrieved 2007-07-27. 21. ^ a b c d e Henderson, Charlie (2007-07-26). "Where now for cycling?". BBC News. Retrieved 2007-08-13. 22. ^ "It has survived over 104 years...I don't think a handful of cheats is going to stop it. But it's going to get to Paris in a very damaged state, just as it did in 1998." per William Fotheringham, journalist with The Guardian on BBC Five Live, 25 July 2007 23. ^ Pretot, Julian (31 July 2007). "Tour vows to continue fight against doping". Times of Malta. Retrieved 24 November 2018. 24. ^ a b c "Sinkewitz fired after confession". BBC News. 2007-08-01. Retrieved 2007-08-01. 25. ^ a b c "Vinokourov fails Tour doping test". BBC News. 2007-07-24. Retrieved 2007-09-04. 26. ^ Gallagher, Brendan (2007-07-26). "Tour in crisis as Vinokourov fails dope test". The Sydney Morning Herald. Retrieved 2007-07-25. 27. ^ Pretot, Julian (30 July 2007). "Vinokourov sacked by Astana team". Reuters. Retrieved 24 November 2018. 28. ^ "Vinokourov fired by Astana team". BBC News. 2007-07-30. Retrieved 2007-08-01. 29. ^ Pugmire, Jerome (25 July 2007). "Italian Rider Taken Away by Police". Washington Post. Retrieved 24 November 2018. 30. ^ "Mayo positif et suspendu". L'Équipe (in French). 2007-07-30. Archived from the original on 2009-08-03. Retrieved 2007-07-30. 31. ^ "Mayo cleared in 'non-negative' test". cyclingnews.com. 2007-06-15. Retrieved 2007-08-02. 32. ^ "Mayo cleared of doping as UCI probes Petacchi, Piepoli". Eurosport. 2007-06-14. Archived from the original on 2007-08-12. Retrieved 2007-07-30. 33. ^ "Mayo's 'B' sample to be re-tested". BBC Sport. 2007-10-23. Retrieved 2007-10-24. 34. ^ Graat, John (2007-07-26). "Deen loog over verblijfplaats / Rabo haalt Rasmussen uit de Tour". Trouw (in Dutch). Retrieved 2007-07-26. 35. ^ "Tour: Rasmussen zat in Italië". Trouw (in Dutch). 2007-07-26. Retrieved 2007-07-26. 36. ^ Møller Johansen, Thomas (2007-07-26). "Rasmussen til B.T.: Min chef er gal" (in Danish). B.T. Archived from the original on 2007-09-30. Retrieved 2007-07-26. 37. ^ Staehelin, Jacob. Michael Rasmussen: Jeg er grædefærdig, B.T. Tour section, p. 3, July 26, 2007. 38. ^ Pugmire, Jerome (2007-07-25). "Tour leader Rasmussen taken out of Tour de France by Rabobank team". CBC. Retrieved 2007-07-27. 39. ^ "Rasmussen powers to mountain win". BBC News. 2007-07-25. Retrieved 2007-09-04. 40. ^ "UCI: Rasmussen står til to års karantæne" (in Danish). politiken.dk. 2007-11-08. Archived from the original on 2008-01-11. Retrieved 2007-11-09. 41. ^ "Riders' commitment to a new cycling". UCI. Archived from the original (PDF) on 2007-09-30. 42. ^ "Alberto Contador, maillot jaune miraculé de l'"opération Puerto"". Le Monde (in French). 2007-07-29. 43. ^ Hood, Andrew (2007-07-24). "Contador on cusp of greatness: Puerto Questions". Velonews. Archived from the original on 2008-07-09. Retrieved 2007-07-27. 44. ^ Vergne, Laurent (2007-07-27). "Contador: "Je suis clair"" (in French). Eurosport. Retrieved 2007-07-27. 45. ^ "'Zege Contador grootste zwendel' (Victory Contador major scam)" (in Dutch). ANP via nu.nl. 2007-07-30. Retrieved 2007-07-30. 46. ^ "Contador: 'I have never doped'". VeloNews. 2007-08-10. Archived from the original on 2008-03-23. Retrieved 2007-08-10. 47. ^ Macur, Juliet (29 September 2010). "With Positive Test, Contador May Lose Tour Title". The New York Times. Archived from the original on 30 September 2010. Retrieved 29 September 2010. 48. ^ "Astana confirm Kashechkin firing". BBC Sport. 31 August 2007. Retrieved 2008-10-17. 49. ^ "Astana banned from Tour of Spain". BBC News. 2007-08-13. Retrieved 2007-08-14. 50. ^ "Rabobank chief resigns after Tour". BBC News. 2007-08-03. Retrieved 2007-08-06. 51. ^ "Contador 'not wanted' in Hamburg". BBC News. 2007-08-08. Retrieved 2007-08-09. 52. ^ Wilson, Bill (2007-07-27). "Tour sponsors taking lead on doping". BBC News. Retrieved 2007-08-06. 53. ^ Holden, Michael (2007-08-02). "2007 Tour de France Review: Part 1". CyclingPost.com. Retrieved 2007-08-06. 54. ^ "Discovery disbands without backer". BBC News. 2007-08-10. Retrieved 2007-08-13. 55. ^ "T-Mobile ends cycling sponsorship". BBC News. 2007-11-27. Retrieved 2007-11-28. 56. ^ "Cycling boss calls for life bans". BBC News. 2007-09-17. Retrieved 2007-09-17. 57. ^ Associated Press (2008-02-13). "Tour de France organizers exclude Astana team; Alberto Contador may not defend title". ESPN.com. Retrieved 2008-08-15. * v * t * e 2007 Tour de France « 2006 2008 » * Teams and cyclists * Prologue–Stage 10 * Stage 11–20 * Doping * v * t * e Doping at the Tour de France By year * 1998 * 1999 * 2007 Related articles * Death of Tom Simpson * Festina affair * Floyd Landis doping case * Lance Armstrong * doping allegations * doping case Related media Books * L.A. Confidentiel * Rough Ride * Seven Deadly Sins: My Pursuit of Lance Armstrong * Wheelmen Films * The Armstrong Lie * The Program * Rough Rider * Tour de Pharmacy [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Doping at the 2007 Tour de France	None	25,682	wikipedia	https://en.wikipedia.org/wiki/Doping_at_the_2007_Tour_de_France	2021-01-18T18:46:47	{"wikidata": ["Q5297321"]}
Lipoid proteinosis (LP) is a rare genodermatosis characterized clinically by mucocutaneous lesions, hoarseness developing in early childhood and, at times, neurological complications. ## Epidemiology Incidence and prevalence are not known. More than 300 cases (ages 6 to 67 years) have been reported worldwide. Most patients are of European ancestry (Dutch or German). A founder effect is reported among large kindreds in South Africa. Many cases are also reported from the Middle East and India. The disease is more commonly seen in consanguineous unions. ## Clinical description A wide range of clinical signs is noted and disease severity is variable, while the course is usually slowly progressive. The usual presenting manifestation is a hoarse cry due to laryngeal infiltration at birth or in infancy. Subsequently, skin and mucous membrane changes develop in the first two years of life. Crusted lesions initially appear on the face and extremities and heal with scarring. Waxy, thickened and at times verrucous skin lesions may affect the face, eyelids, axillae, knees and scrotum. Eyelid beading (moniliform blepharosis) is a hallmark feature but occurs later in childhood. Patchy or diffuse hair loss may be present. The oral mucosa is often involved with cobblestone lips, tongue or gingiva, impaired tongue mobility causing speech problems, and transient swelling and ulceration of the lips and tongue. Oligodontia (see this term) may be present. Respiratory tract infiltration may cause upper respiratory tract infections, hoarseness or aphonia, dysphagia, and airway obstruction. Dystonia, seizures, behavioral changes, learning difficulties and short stature have been reported in affected children. Less commonly, the disease manifests in adulthood with subtle skin findings and possible complications due to visceral deposition. Heterozygous carriers are generally asymptomatic but may have a mild presentation including abnormal dentition. ## Etiology LP is caused by deposition of an amorphous hyaline material in the skin, mucosa, and viscera. Causative loss-of-function mutations have been found in the ECM1 gene (1q21) encoding extracellular matrix protein 1, which has a role in physiology and homeostasis of the skin and many other tissues. ## Diagnostic methods Diagnosis is based on the clinical signs (particularly hoarseness and skin manifestations). Histological findings on biopsy of affected cutaneous or mucosal sites show periodic acid-Schiff-positive deposition of amorphous hyaline material in the papillary dermis which confirms the diagnosis. Cranial magnetic resonance imaging or computed tomography reveals bean-shaped intracerebral calcifications in the temporal lobe (in up to 75% of patients). Molecular genetic testing confirms the diagnosis. ## Differential diagnosis The main differential diagnoses are hydroa vacciniforme and autosomal erythropoietic protoporphyria, but also include leprosy, lichen amyloidosis (see these terms), and xanthomas. ## Antenatal diagnosis If a family member is affected by the disease and the gene mutation has been confirmed, prenatal diagnosis is possible. ## Genetic counseling LP is inherited in an autosomal recessive manner. Genetic counseling should be provided to affected families. ## Management and treatment There is currently no known effective curative treatment and no standard treatment approach. D-penicillamine, oral dimethyl sulfoxide, acitretin, topical corticosteroids, and carbon dioxide laser have been used with varying degrees of success. Treatment of LP with acitretin has shown some efficacy for hoarseness after use over a long period, but there has been variable success in treating the skin lesions. ## Prognosis The prognosis is generally favorable. Fatal outcomes are uncommon, but the disease may strongly impact quality of life. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Lipoid proteinosis	c0023795	25,683	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=530	2021-01-23T17:40:43	{"gard": ["3268"], "mesh": ["D008065"], "omim": ["247100"], "umls": ["C0023795"], "icd-10": ["E78.8"], "synonyms": ["Hyalinosis cutis et mucosae", "Urbach-Wiethe disease"]}
Pericardial effusion A 2D transthoracic echocardiogram of pericardial effusion. The "swinging" heart SpecialtyCardiac surgery A pericardial effusion is an abnormal accumulation of fluid in the pericardial cavity. The pericardium is a 2-part membrane surrounding the heart: the outer fibrous connective membrane and an inner 2-layered serous membrane. The 2 layers of the serous membrane enclose the pericardial cavity ("space") between them. [1]This pericardial space contains a small amount of fluid, referred to as the pericardial fluid. The fluid is normally 15-50 mL in volume.[2] The pericardium, specifically the pericardial fluid provides lubrication, maintains the anatomic position of the heart in the chest, and also serves as a barrier to protect the heart from infection and inflammation in adjacent tissues and organs. [3] By definition, a pericardial effusion occurs when the volume of fluid in the cavity exceeds the normal limit.[4] Some of the presenting symptoms are dyspnea, chest pressure/pain, and malaise. Important etiologies of pericardial effusions are inflammatory, infectious, neoplastic, traumatic, and metabolic causes. Echocardiogram, CT and MRI are the most common methods of diagnosis, although chest X-ray and EKG are also performed in most patients. Pericardiocentesis may be diagnostic as well as therapeutic (form of treatment). These topics are further discussed in detail below. ## Contents * 1 Pathophysiology * 2 Signs and symptoms * 3 Physical exam findings * 4 Causes * 5 Diagnosis * 6 Treatment * 7 References * 8 External links ## Pathophysiology[edit] Pericardial effusion progresses to cardiac tamponade when the accumulated fluid compresses the heart How much fluid is stored in the pericardial sac at one particular time is based on the balance between production and reabsorption. Studies have shown that much of the fluid that accumulates in the pericardial sac is from plasma filtration of the epicardial capillaries and a small amount from the myocardium, while the fluid that is drained is mostly via the parietal lymphatic capillaries. [3] Pericardial effusion usually results from a disturbed equilibrium between these two processes or from a structural abnormality that allows excess fluid to enter the pericardial cavity.[3] Because of the limited amount of anatomic space in the pericardial cavity and the limited elasticity of the pericardium, fluid accumulation beyond the normal amount leads to an increased intrapericardial pressure which can negatively affect heart function. A pericardial effusion with enough pressure to adversely affect heart function is called cardiac tamponade.[1] Pericardial effusions can cause cardiac tamponade in acute settings with fluid as little as 150mL. In chronic settings, however, fluid can accumulate anywhere up to 2L before an effusion causes cardiac tamponade. The reason behind this is the elasticity of the pericardium. When fluid fills the cavity rapidly, the pericardium cannot stretch rapidly, but in chronic effusions, the gradual fluid collection provides the pericardium enough time to accommodate and stretch with the increasing fluid levels.[2] ## Signs and symptoms[edit] Pericardial effusion presentation varies from patient to patient depending on the size, acuity and underlying cause of the effusion.[4] Some patients may be asymptomatic and the effusion may be an incidental finding on an exam.[1] Others with larger effusions may present with chest pressure or pain, dyspnea, shortness of breath, and malaise (a general feeling of discomfort or illness). Yet others with cardiac tamponade, a life-threatening complication, may present with dyspnea, low blood pressure, weakness, restlessness, hyperventilation (rapid breathing), discomfort with laying flat, dizziness, syncope or even loss of consciousness.[2] Patient’s may also present with non-cardiac symptoms due to the enlarging pericardial effusion compressing nearby structures. Some examples are nausea and abdominal fullness, dysphagia and hiccups, due to compression of stomach, esophagus, and phrenic nerve respectively.[5] ## Physical exam findings[edit] Patients with pericardial effusion may have unremarkable physical exams but often present with tachycardia, distant heart sounds and tachypnea.[4] A physical finding specific to pericardial effusion is dullness to percussion, bronchial breath sounds and egophony over the inferior angle of the left scapula. This phenomenon is known as Ewart's sign and is due to compression of the left lung base.[2] Patients with concern for cardiac tamponade may present with abnormal vitals and what's classically known as the Beck's triad, which consists of hypotension (low blood pressure), jugular venous distension and distant heart sounds. Though these are the classical findings; all three occur simultaneously in only a minority of patients.[1] Patients presenting with cardiac tamponade may also be evaluated for pulsus paradoxus. Pulsus paradoxus is a phenomenon in which systolic blood pressure drops by 10 mmHg or more during inspiration. In cardiac tamponade, the pressure within the pericardium is significantly higher, hence decreasing the compliance of the chambers (the capacity to expand/ conform to volume changes). During inspiration, right ventricle filling in increased, which causes the Interventricular septum to bulge into the left ventricle, hence leading to reduced left ventricular filling and consequently reduced stroke volume and low systolic blood pressure.[2] ## Causes[edit] Any process that leads to injury or inflammation of the pericardium and/or inhibits appropriate lymphatic drainage of the fluid from the pericardial cavity leads to fluid accumulation.[5] Pericardial effusions can be found in all populations worldwide but the predominant etiology has changed over time, varying depending on the age, location, and comorbidities of the population in question. [2] Out of all the numerous causes of pericardial effusion, some of the leading causes are inflammatory, infectious, neoplastic and traumatic. These causes can be categorized into various classes, but an easy way to understand them is dividing them into inflammatory versus non-inflammatory. A pericardial effusion due to pericarditis Inflammatory Causes:[5] 1. Infectious: * Viral: coxsackie A and B viruses, HIV (seen in 5-43% of HIV patients),[2] hepatitis viruses, parvovirus B19 * Bacterial: Mycobacterium (tuberculosis), gram positive cocci (Streptococcus, Staphylococcus), Mycoplasma, Neisseria (meningitides, gonorrhea), Coxiella burnetii. Tuberculosis is the leading cause of pericardial effusion in the developing world, with the mortality rate ranging from 17-40%.[5] * Fungal: Histoplasma, Candida * Protozoal: Echinococcus, Trichinosis, Toxoplasma 2. Cardiac injury syndromes: Heart surgery[6] (postpericardiotomy syndrome), post-myocardial infarction (Dressler's syndrome), coronary interventions such as drug eluting stents. Post-cardiac surgery pericardial effusions contribute to 54% of total effusions in the pediatric population. 3. Cardiac inflammation: idiopathic pericarditis is the most common inflammatory cause of pericardial effusion in the United States. [7] 4. Autoimmune: lupus, rheumatoid arthritis,[8] Sjögren syndrome, scleroderma, Dressler's syndrome, sarcoidosis 5. Drug hypersensitivity/ side effects: Chemotherapy drugs (doxorubicin and cyclophosphamide), Minoxidil 6. Others: kidney failure, uremia Non-Inflammatory Causes:[5] 1. Neoplastic: pericardial effusions may present as primary manifestations of underlying malignancy in patients.[5] * Primary tumor: the most common primary pericardial tumor is mesothelioma. Various imaging appearances such as solid and cystic components could be encountered on CT scan on those with mesothelioma. Other less common primary tumors are sarcoma, lymphoma, and primitive neuroectodermal tumour.[9] * Secondary Cancers: that have spread to the pericardium such as breast and lung cancer. Pericardial irregular thickening and/or nodularity, focal, or diffuse FDG uptake on PET scan and lack of preserved fat plane with an adjacent tumor are strongly suggestive of cancer spread from other parts of the body.[9] 2. Metabolic: hypothyroidism(myxedema coma), severe protein deficiency 3. Traumatic: penetrating or blunt chest trauma, aortic dissection 4. Reduced lymphatic drainage: congestive heart failure, nephrotic syndrome ## Diagnosis[edit] Chest X-ray showing a massive pericardial effusion: Water bottle sign EKG: sinus tachycardia with low QRS voltage and electrical alternans Some patients with pericardial effusions may present with no symptoms and the diagnosis can be an incidental finding due to imaging of other illnesses. Patients who present with dyspnea or chest pain have a broad differential diagnosis and it may be necessary to rule out other causes like myocardial infarction, pulmonary embolism, pneumothorax, acute pericarditis, pneumonia, and esophageal rupture.[2] Initial tests include electrocardiography (ECG) and chest x-ray. Chest x-ray: is non-specific and may not help identify a pericardial effusion but a very large, chronic effusion can present as "water-bottle sign" on an x-ray, which occurs when the cardiopericardial silhouette is enlarged and assumes the shape of a flask or water bottle.[2] Chest radiograph is also helpful in ruling out pneumothorax, pneumonia, and esophageal rupture. ECG: may present with sinus tachycardia, low voltage QRS as well as electrical alternans.[2] Due to the fluid accumulation around the heart, the heart is further away from the chest leads, which leads to the low voltage QRS. Electrical alternans signifies the up-and-down change of the QRS amplitude with every beat due to the heart swinging in the fluid (as displayed in the ultrasound image in the introduction) .[1] These three findings together should raise suspicion for impending hemodynamic instability associated with cardiac tamponade. Echocardiogram (ultrasound): when pericardial effusion is suspected, echocardiography usually confirms the diagnosis and allows assessment of the size, location and signs of hemodynamic instability.[5] A transthoracic echocardiogram (TTE) is usually sufficient to evaluate pericardial effusion and it may also help distinguish pericardial effusion from pleural effusion and MI. Most pericardial effusions appear as an anechoic area (black or without an echo) between the visceral and the parietal membrane.[1] Complex or malignant effusions are more heterogeneous in appearance, meaning they may have variations in echo on ultrasound.[4] TTE can also differentiate pericardial effusion based on the size. Although it's difficult to define size classifications because they vary with institutions, most commonly they are as follows: small <10, moderate 10-20, large >20\. [4]An echocardiogram is urgently needed for evaluation when there is concern for hemodynamic compromise, a rapidly developing effusion or history of recent cardiac surgery/procedures.[1] Cardiac CT and MRI scans: cross-sectional imaging with computed tomography (CT) can help localize and quantify the effusion, especially in a loculated effusion (a effusion contained to one area).[10] CT imaging also helps assess for pericardial pathology (pericardial thickening, constrictive pericarditis, malignancy-associated pericarditis).[1] Whereas cardiac MRI is reserved for patients with poor echocardiogram findings and for assessing pericardial inflammation, especially for patients with continued inflammation despite treatment.[4] CT and MRI imaging can also be used for continued follow up on patients. Pericardiocentesis: is a procedure in which fluid is aspirated from the pericardial cavity with a needle and catheter. This procedure can be used to analyze the fluid but more importantly can also provide symptomatic relief, especially in patients with hemodynamic compromise. Pericardiocentesis is usually guided by an echocardiogram to determine the exact location of the effusion and the optimal location of puncture site to minimize risk of complications.[4] After the procedure, the aspirated fluid is analyzed for gross appearance (color, consistency, bloody), cell count, and concentration of glucose, protein, and other cellular components (for example lactate dehydrogenase).[11] Fluid may be also sent for gram stain, acid fast stain, or culture if high suspicion of infectious cause. [1] Bloody fluids may also be evaluated for malignant cells.[11] Fluid analysis may result in: * transudative effusion: due to non-inflammatory causes (congestive heart failure , myxoedema , nephrotic syndrome ) * exudative effusion: inflammatory or malignant causes (tuberculosis , spread from empyema , metastasis) * hemorrhagic effusion: high blood concentration (trauma, rupture of aneurysms, malignant effusion) * A CT scan showing a pericardial effusion * A large anechoic (black) pericardial effusion as seen on ultrasound. Closed arrow: the heart, open arrow: the effusion * Pericardial effusion due to malignancy. Note bulbous heart and primary lung cancer in right upper lobe. * Pericardiocentesis: fluid aspiration of hemorrhagic effusion ## Treatment[edit] Treatment depends on the underlying cause and the severity of the heart impairment.[1] For example, pericardial effusion from autoimmune etiologies may benefit from anti-inflammatory medications. Pericardial effusion due to a viral infection usually resolves within a few weeks without any treatment.[7] Small pericardial effusions without any symptoms don't require treatment and may be watched with serial ultrasounds.[2] If the effusion is compromising heart function and causing cardiac tamponade, it will need to be drained.[1] Fluid can be drained via needle pericardiocentesis as discussed above or surgical procedures, such as a pericardial window.[2] The intervention used depends on the cause of pericardial effusion and the clinical status of the patient. Pericardiocentesis is the choice of treatment in unstable patients: it can be performed at the bedside and in a timely manner.[5]A drainage tube is often left in place for 24 hours or more for assessment of re-accumulation of fluid and also for continued drainage.[5] Patients with cardiac tamponade are also given IV fluids and/or vasopressors to increase systemic blood pressure and cardiac output.[1] But in localized or malignant effusions, surgical drainage may be required instead. This is most often done by cutting through the pericardium and creating a pericardial window[1] This window provides a path for the fluid to be drained directly into the chest cavity, which prevents future development of cardiac tamponade. In localized effusions, it might be difficult to get safe access for pericardiocentesis, hence a surgical procedure is preferred. In case of malignant effusions, the high likelihood of recurrence of fluid accumulation is the main reason for a surgical procedure.[5] Pericardiocentesis is not preferred for chronic treatment options due to risk of infection. ## References[edit] 1. ^ a b c d e f g h i j k l m Phelan, D., Collier, P., Grimm, R. Pericardial Disease. Cleveland Clinic. July 2015. Retrieved Nov 2020. 2. ^ a b c d e f g h i j k l Willner, Daniel A.; Goyal, Amandeep; Grigorova, Yulia; Kiel, John (2020), "Pericardial Effusion", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 28613741, retrieved 2020-11-12 3. ^ a b c Vogiatzidis, Konstantinos et al. “Physiology of pericardial fluid production and drainage.” Frontiers in physiology vol. 6 62. 18 Mar. 2015, doi:10.3389/fphys.2015.00062 4. ^ a b c d e f g McIntyre, William F.; Jassal, Davinder S.; Morris, Andrew L. (2015-06-01). "Pericardial Effusions: Do They All Require Pericardiocentesis?". Canadian Journal of Cardiology. 31 (6): 812–815. doi:10.1016/j.cjca.2015.01.006. ISSN 0828-282X. 5. ^ a b c d e f g h i j Vakamudi, Sneha et al. “Pericardial Effusions: Causes, Diagnosis, and Management.” Progress in cardiovascular diseases vol. 59,4 (2017): 380-388. doi:10.1016/j.pcad.2016.12.009 6. ^ Pericardial effusion:What are the symptoms?, Dr. Martha Grogan M.D. 7. ^ a b Imazio M, Gaita F, LeWinter M. Evaluation and Treatment of Pericarditis: A Systematic Review. JAMA. 2015;314(14):1498–1506. doi:10.1001/jama.2015.12763 8. ^ Hallewell RA, Sherratt DJ (1976). "Isolation and characterization of Co1E2 plasmid mutants unable to kill colicin-sensitive cells". Mol Gen Genet. 146 (3): 239–45. doi:10.1007/bf00701246. PMID 794689. 9. ^ a b Ünal, Emre; Karcaaltincaba, Musturay; Akpinar, Erhan; Ariyurek, Orhan Macit (December 2019). "The imaging appearances of various pericardial disorders". Insights into Imaging. 10 (1): 42. doi:10.1186/s13244-019-0728-4. ISSN 1869-4101. PMC 6441059. PMID 30927107. 10. ^ Chang, S (Jul–Sep 2014). "Brief Images: Massive pericardial effusion". Images in Paediatric Cardiology. 16 (3): 1–3. PMC 4521324. PMID 26236369. 11. ^ a b Kopcinovic, Lara Milevoj, and Jelena Culej. “Pleural, peritoneal and pericardial effusions - a biochemical approach.” Biochemia medica vol. 24,1 123-37. 15 Feb. 2014, doi:10.11613/BM.2014.014 ## External links[edit] Classification D * ICD-10: I30, I31.3 * ICD-9-CM: 423.9 * MeSH: D010490 * DiseasesDB: 2128 External resources * eMedicine: med/1786 * Patient UK: Pericardial effusion * 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-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Pericardial effusion	c0031039	25,684	wikipedia	https://en.wikipedia.org/wiki/Pericardial_effusion	2021-01-18T19:01:26	{"mesh": ["D010490"], "umls": ["C0031039"], "icd-9": ["423.9"], "icd-10": ["I31.3", "I30"], "wikidata": ["Q1306218"]}
Mercury poisoning is caused mainly through ingestion or inhalation of any of the 3 forms of mercury, elemental, organic, and inorganic. Exposure to elemental mercury affects the pulmonary (inhalation of mercury vapors causes coughing, chills, fever, shortness of breath), dermatological (mild swelling, vesiculation, scaling, irritation, urticaria, erythema and allergic contact dermatitis accompanied by pain), and peripheral and central nervous (CNS) systems (depression, paranoia, extreme irritability, hallucinations, inability to concentrate, memory loss, hands, head, lips, tongue, jaw and eyelids tremors, weight loss, perpetually low body temperature, drowsiness, headaches, insomnia, fatigue). Exposure to inorganic mercury generally causes development of a metallic taste, local oropharyngeal pain, nausea, vomiting, bloody diarrhea, colic abdominal pain, renal dysfunction and, neurologic abnormalities; while that to organic mercury can lead to delayed neurotoxicity. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Mercury poisoning	c0025427	25,685	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=330021	2021-01-23T17:40:10	{"gard": ["7021"], "mesh": ["D008630"], "umls": ["C0025427"], "icd-10": ["T56.1"], "synonyms": ["Hydrargyria", "Mercurialism", "Mercury intoxication"]}
Tarsal kink syndrome is a rare congenital malformation of the tarsus that causes entropion characterized by blepharospasm and absence of an upper eyelid fold that may lead to corneal ulceration caused by the folded edge of the upper tarsus or the inturned eyelashes if not corrected by surgery. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Tarsal kink syndrome	None	25,686	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99170	2021-01-23T17:54:32	{}
## Description Classic Hodgkin lymphoma is a malignancy of B-cell origin in which the neoplastic cells, known as 'Reed-Sternberg' (RS) cells, are characteristically binucleated (summary by Salipante et al., 2009). See also 236000. Inheritance Hafez et al. (1985) estimated that the heritable component of Hodgkin disease is as high as one-third. Additional evidence supporting an inherited predisposition comes from twin studies, racial-incidence patterns, and occurrences of multiplex families. Observations in a small number of affected relative pairs suggested the presence of an HLA-linked locus (Chakravarti et al., 1986), but this could account for only a minority of the familial risk observed in proband studies (Shugart and Collins, 1998). Leri-Weill dyschondrosteosis (LWD; 127300) is a skeletal dysplasia characterized by short stature, shortened forelimbs, and distal radioulnar (Madelung) deformity. This entity had long been thought to be inherited as an autosomal disorder, presumably autosomal dominant, but was subsequently shown to be due to mutation, deletion, or other disruption of the SHOX gene (312865), which is located in the pseudoautosomal region (PAR). In the epidemiology of Hodgkin disease, an increased frequency of sex concordance among affected sib pairs has suggested pseudoautosomal linkage (see also 400021). Furthermore, Gokhale et al. (1995) reported a pair of sisters with both Hodgkin disease and LWD. There was a multigenerational, maternal history of LWD, and, in maternal relatives, a further history of Hodgkin disease without known LWD. Gokhale et al. (1995) raised the possibility that either LWD and Hodgkin disease results from a mutation deleting adjacent genes responsible for both illnesses, or that genes for the 2 diseases are linked. At the time of report by Gokhale et al. (1995), LWD was attributed to autosomal dominant inheritance. A unique pattern of inheritance is expected from mutations in a gene in the PAR. If the locus were situated on the centromeric portion of the short-arm PAR, proximal to the invariant recombination, then the mutant allele would consistently segregate, during male meiosis, with sexual phenotype. A man could possess the mutant allele on either his X or Y chromosome. If it were on the X chromosome, then only his daughters would inherit the allele, whereas if it resided on the Y chromosome, only his sons would inherit the allele. A similar prediction pertains to loci situated on the long-arm PAR, where recombination between the X and Y chromosomes is rare. In the case of paternal inheritance of a gene situated at the telomeric boundary of the short-arm PAR, where recombination probability is 0.5, there would be no difference with a random sex distribution, and sex-discordant and sex-concordant sib pairs would be equally probable. Since the mutant allele can reside on either of a woman's X chromosomes, maternal inheritance would result in random segregation with sex. Overall, there should be a deficiency of sex-discordant, compared with sex-concordant, affected sib pairs, with the magnitude of the difference being twice as great for a recessive gene as for a dominant gene and lessening with closing proximity to the telomere. Indeed, an excess of sex-concordant sib pairs with Hodgkin disease was noted by Grufferman et al. (1977). Mapping Horwitz and Wiernik (1999) tested the hypothesis that there is a PAR-localized gene for Hodgkin disease. By first scoring recombinations dissociating sex from phenotype in individuals from pedigrees with LWD, they determined a male maximum recombination frequency of 0.405. This placed SHOX, the gene mutant in LWD, near the short-arm telomeres of the sex chromosome and supported the prediction that PAR recombination is obligatory for spermatogenesis. By inferring recombinations between Hodgkin disease and sexual phenotype in sib pairs, they predicted, for the postulated Hodgkin disease gene, a male theta (max) as high as 0.254, which placed it in proximity to SHOX. The nonparametric affected-sib-pair 'beta' model of Morton was used in the evaluation of linkage between Hodgkin disease and phenotypic sex and gave a lod score of 2.41. Using this approach, Horwitz and Wiernik (1999) reevaluated evidence for HLA linkage in Hodgkin disease in haplotyped sib pairs and found a lod score of 2.00. The resulting beta values indicated that the putative PAR-linked and HLA-linked loci account for 29% and 40%, respectively, of the heritability of Hodgkin disease in an American population. Whittemore and Shih (2000) commented on the work of Horwitz and Wiernik (1999). Using microsatellite marker analysis and FISH, Shears et al. (2003) further studied the PAR in the family reported by Gokhale et al. (1995). Results confirmed that the 2 sibs with Hodgkin disease and LWD each harbored a maternally inherited microdeletion within the PAR, encompassing the SHOX gene, estimated to be 900 kb and located between 200 and 1,100 kb from the Xp telomere. Three genes of potential importance in Hodgkin lymphoma located within the PAR--IL3RA (308385), CSF2RA (306250), and MIC2 (313470)--were not within the deleted region in the 2 sibs. Although it was not possible to exclude haploinsufficiency due to the deletion of some unknown tumor suppressor gene, an intriguing possibility was that the PAR deletion caused a long-range position effect by downregulating expression of 1 of the above genes. MIC2 was considered a particularly strong candidate as decreased expression had been found to be associated with the generation of cells with Hodgkin and Reed-Sternberg phenotype (Kim et al., 1998). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	LYMPHOMA, HODGKIN, X-LINKED PSEUDOAUTOSOMAL	c0019829	25,687	omim	https://www.omim.org/entry/300221	2019-09-22T16:20:38	{"doid": ["8567"], "mesh": ["D006689"], "omim": ["236000", "300221"], "orphanet": ["391"], "synonyms": ["Classic Hodgkin disease", "Alternative titles", "HODGKIN DISEASE, X-LINKED PSEUDOAUTOSOMAL"]}
A rare dermatosis, which can be either localized or systemic, that occurs after prolonged contact and absorption of silver containing compounds over a period of years and that is characterized by irreversible blue-gray to gray-black staining of skin, fingernails and/or mucous membranes, most evident on sun exposed areas of the skin. Silver exposure is usually occupational but may also occur through dental amalgams, the ingestion of colloidal silver, acupuncture needles, orthopedic implants and topical medications (such as silver sulfadiazine). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Argyria	c0003782	25,688	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=60014	2021-01-23T17:18:30	{"mesh": ["D001129"], "umls": ["C0003782"], "icd-10": ["T56.8"], "synonyms": ["Silver staining"]}
The topic of this article may not meet Wikipedia's general notability guideline. Please help to demonstrate the notability of the topic by citing reliable secondary sources that are independent of the topic and provide significant coverage of it beyond a mere trivial mention. If notability cannot be shown, the article is likely to be merged, redirected, or deleted. Find sources: "Demonophobia" – news · newspapers · books · scholar · JSTOR (November 2014) (Learn how and when to remove this template message) Demonophobia (or daemonophobia) is a fear of demons,[1] a type of specific phobia. It was first described in the 13th century and common in the 16th century but has since mostly disappeared.[2] ## See also[edit] * Demonomania * Demonomaniac ## References[edit] 1. ^ "Definition of Demonophobia". MedicineNet, Inc. Retrieved 9 December 2014. 2. ^ Beck, Aaron; Emery, Gary; Greenberg, Ruth (2005). Anxiety Disorders and Phobias: A Cognitive Perspective. Basic Books. p. 117. ISBN 046500587X. This psychology-related article is a stub. You can help Wikipedia by expanding it. * v * t * e This Christianity-related article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Demonophobia	None	25,689	wikipedia	https://en.wikipedia.org/wiki/Demonophobia	2021-01-18T18:29:00	{"wikidata": ["Q18351141"]}
Cranio-lenticulo-sutural dysplasia Other namesBoyadjiev–Jabs syndrome Protein SEC23A involved in CLSD Cranio-lenticulo-sutural dysplasia (CLSD, or Boyadjiev–Jabs syndrome) is a neonatal/infancy disease caused by a disorder in the 14th chromosome. It is an autosomal recessive disorder, meaning that both recessive genes must be inherited from each parent in order for the disease to manifest itself. The disease causes a significant dilation of the endoplasmic reticulum in fibroblasts of the host with CLSD. Due to the distension of the endoplasmic reticulum, export of proteins (such as collagen) from the cell is disrupted. The production of SEC23A protein is involved in the pathway of exporting collagen (the COPII pathway), but a missense mutation causes and underproduction of SEC23A which inhibits the pathway, affecting collagen secretion.[1] This decrease in collagen secretion can lead to the bone defects that are also characteristic of the disease, such as skeletal dysplasia and under-ossification. Decreased collagen in CLSD-affected individuals contributes to improper bone formation, because collagen is a major protein in the extracellular matrix and contributes to its proper mineralization in bones. It has also been hypothesized that there are other defects in the genetic code besides SEC23A that contribute to the disorder. ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 3 Mechanism * 4 Diagnosis * 4.1 Classification * 5 Treatment * 6 Prognosis * 7 Frequency * 8 History * 9 Current research * 10 References * 11 External links ## Signs and symptoms[edit] The following are symptoms characteristic with individuals having the disorder. Individuals may display some, most, or all of these symptoms throughout the course of their life, though symptoms may vary with each patient.[2] * Abnormal hair (coarse, thick, brittle) * Calvarial hypomineralization (soft skull) * Y-shaped cataracts by 1–2 years of age * Skeletal defects * Hypertelorism (wide-set eyes) * Facial dysmorphisms * Late-closing fontanels * Abnormal accumulation of proteins in the endoplasmic reticulum * Scoliosis * Broad forehead, nose * Missing, small teeth or abnormal teeth positioning * Poor skull calcification * Flat foot * Motor delay * Abnormal vertebrae * Prominent forehead and brow * High nose bridge * Capillary hemangioma * Delayed tooth eruption * Long upper lip groove * Large mouth * High arched palate * Narrow hips and rib cage * Thin lips * Narrow and sloping shoulders * Hyperpigmentation * Hyperextensible joints Onset of the disease is in neonatal development and infancy, and symptoms tend to become evident soon after birth. ## Pathophysiology[edit] CLSD is caused by a missense mutation in the 14q13-q21 region of Chromosome 14, where the amino acid phenylalanine is mistranslated and replaced with leucine. Amino acid sequences are encoded in the DNA of each cell in an organism, which is transcribed into RNA and then translated in a ribosome (in this case, the ribosome is attached to the endoplasmic reticulum) which produces a chain of amino acids which makes up a protein. If an amino acid sequence isn't correct, it won't make a functional protein. The missense mutation in CLSD causes an inactivation of the SEC23A protein, which is responsible for closure of the COPII pathway.[citation needed] Chromosome 14, the chromosome affected by CLSD. ## Mechanism[edit] The main function of the SEC23A protein is to hydrolyze or break down a guanosine triphosphate (GTP) molecule bound to the SAR1A protein at the start of the COPII pathway.[1] The energy released from the breaking of the GTP bond provides energy necessary to undergo another reaction. This triggers uncoating of the vesicle (a membrane bound carrying compartment for molecules) containing a secretory protein destined for packaging in the Golgi apparatus of the cell. Uncoating the vesicle exposes SNARE proteins which are needed for the vesicle to bind to the membrane site on the endoplasmic reticulum. A mutation in the SEC23A gene prevents the vesicle from uncoating so it will not bind to the receptor site on the endoplasmic reticulum to be released into the cytoplasm for transport to the Golgi apparatus.[3] Thus, the vesicles will accumulate in the endoplasmic reticulum, causing it to become enlarged or distended. Ultimately, this causes the craniofacial symptoms present in patients with CLSD. This is probably due to abnormal secretion of collagen and possibly other secretory proteins which have accumulated in the endoplasmic reticulum. Collagen is responsible to for skull ossification, among other things. ## Diagnosis[edit] ### Classification[edit] * Rare developmental anomaly during embryogenesis[3] * Rare genetic disease * Rare bone disease ## Treatment[edit] Treatment for CLSD is largely focused on treating the symptoms of the disorder, because it is still in the early stages of research. Symptomatic treatment is also the only option due to the genetic nature of the disorder. Treatment may include surgeries to correct facial and cranial dysmorphisms or therapy sessions to help alleviate behavioral abnormalities associated with the disorder.[citation needed] ## Prognosis[edit] Though the children affected with CLSD will have problems throughout life, the treatment for this disease thus far is symptomatic. However, prognosis is good; at the time of the most recently published articles, identified children were still alive at over 4 years of age.[4] Mutant proteins still maintain some residual activity, allowing for the release of some collagen, but still form an extremely distended endoplasmic reticulum.[citation needed] ## Frequency[edit] * Birth defects with symptoms related to CLSD are estimated to affect one in every 500 to 1,000 babies in the United States of America[5] * Recommended that CLSD is evaluated in all patients with late-closing fontanels and hypertelorism * Recent case found in a caucasian male with a SEC23 inherited mutation from the father combined with another unknown mutation that leads to the symptoms of CLSD despite a healthy gene inherited from the mother[4] * Measurement of parental and patient endoplasmic reticulums show distention in both the father and the child, but not the mother as compared to a control measurement. The child was significantly more distended than the father and the mother.[4] * Frequency of the disorder may be greater than once thought, and may be linked more closely to all cases of late-closing fontanels and hypertelorism ## History[edit] Cranio-lenticulo-sutural dysplasia was first discovered by Simeon Boyadjiev Boyd, chief of the Section of Genetics at UC Davis Children's Hospital, in 2003. CLSD was found a consanguineous (sharing a common ancestor) Saudi Arabian family of Bedouin descent. The children who were affected inherited the defective gene from both of their parents (Boyadjiev, 1193). A Caucasian male was also found to have symptoms of the disease, but possessed only one defective chromosome. Measurements of the endoplasmic reticulums of his mother and father showed that the mother had a normal phenotype, the father had a slightly distended endoplasmic reticulum, and the affected son had an endoplasmic reticulum distended to a much greater extent. Because of the normal measurements obtained from the mother, it was concluded that the father was responsible for the son's symptoms and was hypothesized that there was another mutation on chromosome 14 that caused the disease to manifest itself without a secondary disease carrying chromosome he would have inherited from his mother.[4] It is associated with a mutation changing the translation of phenylalanine to leucine in SEC23A.[3] ## Current research[edit] Taking advantage of the transparent embryos of zebrafish, these organisms were bred with the SEC23A mutation and observed for developmental issues. These can give a clue to symptoms that cannot be observed in the womb of a human.[3] Observations include: * expression in developing head cartilage * expression in all main neurocranial and vicerocranial cartilages of the head * scapulocoracoid and postcoracoid processes of the pectoral fin and distal edge of endoskeletal disc * shortened overall body length[5] ## References[edit] 1. ^ a b Bi, X; Mancias, JD; Goldberg, J (Nov 2007). "Insights into COPII coat nucleation from the structure of Sec23.Sar1 complexed with the active fragment of Sec31". Developmental Cell. 13 (5): 635–45. doi:10.1016/j.devcel.2007.10.006. PMC 2686382. PMID 17981133. 2. ^ "Symptoms of Craniolenticulosutraldysplasia." Right Diagnosis. Healthgrades. Web. 10 February 2014. http://www.rightdiagnosis.com/c/craniolenticulosutural_dysplasia/symptoms.htm 3. ^ a b c d Boyadjiev SA, Fromme JC, Ben J, et al. (October 2006). "Cranio-lenticulo-sutural dysplasia is caused by a SEC23A mutation leading to abnormal endoplasmic-reticulum-to-Golgi trafficking". Nat. Genet. 38 (10): 1192–7. doi:10.1038/ng1876. PMID 16980979. S2CID 21756330. 4. ^ a b c d Boyadjiev, S.A., Kim, S.-D., Hata, A., Haldeman-Englert, C., Zackai, E., Naydenov, C., Hamamoto, S., Schekman, R. and Kim, J. (2011), Cranio-lenticulo-sutural dysplasia associated with defects in collagen secretion. Clinical Genetics, 80: 169–176. doi:10.1111/j.1399-0004.2010.01550 5. ^ a b Genetic Mutation Identified as Cause of Cranio-lenticulo-sutural Dysplasia. (October 11, 2012). RxPG News. http://www.rxpgnews.com/genetics/Genetic_mutation_identified_as_cause_of_cranio-len_5012_5012.shtml ## External links[edit] Classification D * ICD-10: Q75.8 * OMIM: 607812 * MeSH: C564332 External resources * Orphanet: 50814 * v * t * e Inherited disorders of trafficking / vesicular transport proteins Vesicle formation Lysosome/Melanosome: * HPS1–HPS7 * Hermansky–Pudlak syndrome * LYST * Chédiak–Higashi syndrome COPII: * SEC23A * Cranio-lenticulo-sutural dysplasia * COG7 * CDOG IIE APC: * AP1S2 * X-linked intellectual disability * AP3B1 * Hermansky–Pudlak syndrome 2 * AP4M1 * CPSQ3 Rab * ARL6 * BBS3 * RAB27A * Griscelli syndrome 2 * CHM * Choroideremia * MLPH * Griscelli syndrome 3 Cytoskeleton Myosin: * MYO5A * Griscelli syndrome 1 Microtubule: * SPG4 * Hereditary spastic paraplegia 4 Kinesin: * KIF5A * Hereditary spastic paraplegia 10 Spectrin: * SPTBN2 * Spinocerebellar ataxia 5 Vesicle fusion Synaptic vesicle: * SNAP29 * CEDNIK syndrome * STX11 * Hemophagocytic lymphohistiocytosis 4 Caveolae: * CAV1 * Congenital generalized lipodystrophy 3 * CAV3 * Limb-girdle muscular dystrophy 2B, Long QT syndrome 9 Vacuolar protein sorting: * VPS33B * ARC syndrome * VPS13B * Cohen syndrome * DYSF * Distal muscular dystrophy See also vesicular transport proteins [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Cranio-lenticulo-sutural dysplasia	c1843042	25,690	wikipedia	https://en.wikipedia.org/wiki/Cranio-lenticulo-sutural_dysplasia	2021-01-18T18:32:06	{"mesh": ["C564332"], "umls": ["C1843042"], "orphanet": ["50814"], "wikidata": ["Q5182157"]}
Severe form of genetic dwarfism that is usually lethal Thanatophoric dysplasia Radiogram of a baby born with thanatophoric dwarfism SpecialtyMedical genetics Thanatophoric dysplasia (thanatophoric dwarfism) is a severe skeletal disorder characterized by a disproportionately small ribcage, extremely short limbs and folds of extra skin on the arms and legs. ## Contents * 1 Symptoms * 2 Causes * 3 Diagnosis * 3.1 Classification * 4 Prognosis * 5 Incidence * 6 References * 7 External links ## Symptoms[edit] Infants with this condition have disproportionately short arms and legs with extra folds of skin. Other signs of the disorder include a narrow chest, small ribs, underdeveloped lungs, and an enlarged head with a large forehead and prominent, wide-spaced eyes. Thanatophoric dysplasia is a lethal skeletal dysplasia divided into two subtypes. Type I is characterized by extreme rhizomelia, bowed long bones, narrow thorax, a relatively large head, normal trunk length and absent cloverleaf skull. The spine shows platyspondyly, the cranium has a short base, and, frequently, the foramen magnum is decreased in size. The forehead is prominent, and hypertelorism and a saddle nose may be present. Hands and feet are normal, but fingers are short. Type II is characterized by short, straight long bones and cloverleaf skull.[1] It presents with typical telephone-handle shaped long bones and H-shaped vertebrae.[citation needed] ## Causes[edit] It can be associated with missense mutations in fibroblast growth factor receptor-3. It is inherited in an autosomal dominant manner.[2][3] ## Diagnosis[edit] ### Classification[edit] Infants with type 1 thanatophoric dysplasia also have curved thigh bones, flattened bones of the spine (platyspondyly) and shortened thoracic ribs. Note: Prenatal ultra-sound images of the ribs sometimes appear asymmetrical when in fact they are not. In certain cases, this has caused a misdiagnosis of Osteogenisis Imperfecta (OI) type II. An unusual head shape called kleeblattschädel ("cloverleaf skull") can be seen with type 2 thanatophoric dysplasia.[4] ## Prognosis[edit] The term thanatophoric is Greek for "death bearing". Children with this condition are usually stillborn or die shortly after birth from respiratory failure. A small number have survived into childhood, and a very few beyond. Survivors have difficulty breathing on their own and require respiratory support such as high flow oxygen through a canula or ventilator support via tracheostomy. There may also be evidence of spinal stenosis and seizures. The oldest known living TD survivor as of 2013 was a 29-year-old woman.[5] One man lived to be 26 years old. Another man lived to age 20. It was reported in 1998 that a 21 year old man with the condition lives in the United States, while two children with TD aged 10 and 12, a boy and a girl, were known in Germany. There was also a 6-year-old boy living with TD and two 1-year old boys.[6] As of 2020 Christopher Álvarez, 23, is a Colombian living with TD in New York City.[7] ## Incidence[edit] This condition affects about 1 in 60,000 births.[8][failed verification] ## References[edit] 1. ^ Norris, Cheryl D., George Tiller, Philippe Jeanty, Srini Malini (2008-12-12). "Thanatophoric dysplasia in monozygotic twins". TheFetus.net. Archived from the original on December 12, 2008. Retrieved 2016-03-01. 2. ^ Bonaventure J, Gibbs L, Horne WC, Baron R (2007). "The localization of FGFR3 mutations causing thanatophoric dysplasia type I differentially affects phosphorylation, processing and ubiquitylation of the receptor". FEBS J. 274 (12): 3078–93. doi:10.1111/j.1742-4658.2007.05835.x. PMID 17509076. 3. ^ Lievens PM, Liboi E (2003). "The thanatophoric dysplasia type II mutation hampers complete maturation of fibroblast growth factor receptor 3 (FGFR3), which activates signal transducer and activator of transcription 1 (STAT1) from the endoplasmic reticulum". J. Biol. Chem. 278 (19): 17344–9. doi:10.1074/jbc.M212710200. PMID 12624096. 4. ^ Norman AM, Rimmer S, Landy S, Donnai D (1992). "Thanatophoric dysplasia of the straight-bone type (type 2)". Clin. Dysmorphol. 1 (2): 115–20. doi:10.1097/00019605-199204000-00008. PMID 1345514. 5. ^ Nikkel, Sarah M.; Major, Nathalie; King, W. James (2013-12-01). "Growth and development in thanatophoric dysplasia – an update 25 years later". Clinical Case Reports. 1 (2): 75–78. doi:10.1002/ccr3.29. ISSN 2050-0904. PMC 4184754. PMID 25356217. 6. ^ Baker, K. M.; Olson, D. S.; Harding, C. O.; Pauli, R. M. (1997). "Long-term survival in typical thanatophoric dysplasia type 1". American Journal of Medical Genetics. 70 (4): 427–436. doi:10.1002/(SICI)1096-8628(19970627)70:4<427::AID-AJMG18>3.0.CO;2-J. PMID 9182787. 7. ^ "TheyWantca Instagram". www.instagram.com. December 30, 2020. 8. ^ Vajo, Zoltan; Francomano CA; Wilkin DJ (2000). "The molecular and genetic basis of fibroblast growth factor receptor 3 disorders: the achondroplasia family of skeletal dysplasias, Muenke craniosynostosis, and Crouzon syndrome with acanthosis nigricans". Endocr. Rev. 21 (1): 23–39. doi:10.1210/er.21.1.23. PMID 10696568. ## External links[edit] * GeneReview/NCBI/NIH/UW entry on Thanatophoric Dysplasia * Thanatophoric dysplasia at NLM Genetics Home Reference Classification D * ICD-10: Q77.1 * OMIM: 187600 * MeSH: D013796 * DiseasesDB: 29403 External resources * eMedicine: ped/2233 * Orphanet: 2655 * v * t * e Osteochondrodysplasia Osteodysplasia// osteodystrophy Diaphysis * Camurati–Engelmann disease Metaphysis * Metaphyseal dysplasia * Jansen's metaphyseal chondrodysplasia * Schmid metaphyseal chondrodysplasia Epiphysis * Spondyloepiphyseal dysplasia congenita * Multiple epiphyseal dysplasia * Otospondylomegaepiphyseal dysplasia Osteosclerosis * Raine syndrome * Osteopoikilosis * Osteopetrosis Other/ungrouped * FLNB * Boomerang dysplasia * Opsismodysplasia * Polyostotic fibrous dysplasia * McCune–Albright syndrome Chondrodysplasia/ chondrodystrophy (including dwarfism) Osteochondroma * osteochondromatosis * Hereditary multiple exostoses Chondroma/enchondroma * enchondromatosis * Ollier disease * Maffucci syndrome Growth factor receptor FGFR2: * Antley–Bixler syndrome FGFR3: * Achondroplasia * Hypochondroplasia * Thanatophoric dysplasia COL2A1 collagen disease * Achondrogenesis * type 2 * Hypochondrogenesis SLC26A2 sulfation defect * Achondrogenesis * type 1B * Autosomal recessive multiple epiphyseal dysplasia * Atelosteogenesis, type II * Diastrophic dysplasia Chondrodysplasia punctata * Rhizomelic chondrodysplasia punctata * Conradi–Hünermann syndrome Other dwarfism * Fibrochondrogenesis * Short rib – polydactyly syndrome * Majewski's polydactyly syndrome * Léri–Weill dyschondrosteosis * v * t * e Cell surface receptor deficiencies G protein-coupled receptor (including hormone) Class A * TSHR (Congenital hypothyroidism 1) * LHCGR (Luteinizing hormone insensitivity, Leydig cell hypoplasia, Male-limited precocious puberty) * FSHR (Follicle-stimulating hormone insensitivity, XX gonadal dysgenesis) * GnRHR (Gonadotropin-releasing hormone insensitivity) * EDNRB (ABCD syndrome, Waardenburg syndrome 4a, Hirschsprung's disease 2) * AVPR2 (Nephrogenic diabetes insipidus 1) * PTGER2 (Aspirin-induced asthma) Class B * PTH1R (Jansen's metaphyseal chondrodysplasia) Class C * CASR (Familial hypocalciuric hypercalcemia) Class F * FZD4 (Familial exudative vitreoretinopathy 1) Enzyme-linked receptor (including growth factor) RTK * ROR2 (Robinow syndrome) * FGFR1 (Pfeiffer syndrome, KAL2 Kallmann syndrome) * FGFR2 (Apert syndrome, Antley–Bixler syndrome, Pfeiffer syndrome, Crouzon syndrome, Jackson–Weiss syndrome) * FGFR3 (Achondroplasia, Hypochondroplasia, Thanatophoric dysplasia, Muenke syndrome) * INSR (Donohue syndrome * Rabson–Mendenhall syndrome) * NTRK1 (Congenital insensitivity to pain with anhidrosis) * KIT (KIT Piebaldism, Gastrointestinal stromal tumor) STPK * AMHR2 (Persistent Müllerian duct syndrome II) * TGF beta receptors: Endoglin/Alk-1/SMAD4 (Hereditary hemorrhagic telangiectasia) * TGFBR1/TGFBR2 (Loeys–Dietz syndrome) GC * GUCY2D (Leber's congenital amaurosis 1) JAK-STAT * Type I cytokine receptor: GH (Laron syndrome) * CSF2RA (Surfactant metabolism dysfunction 4) * MPL (Congenital amegakaryocytic thrombocytopenia) TNF receptor * TNFRSF1A (TNF receptor associated periodic syndrome) * TNFRSF13B (Selective immunoglobulin A deficiency 2) * TNFRSF5 (Hyper-IgM syndrome type 3) * TNFRSF13C (CVID4) * TNFRSF13B (CVID2) * TNFRSF6 (Autoimmune lymphoproliferative syndrome 1A) Lipid receptor * LRP: LRP2 (Donnai–Barrow syndrome) * LRP4 (Cenani–Lenz syndactylism) * LRP5 (Worth syndrome, Familial exudative vitreoretinopathy 4, Osteopetrosis 1) * LDLR (LDLR Familial hypercholesterolemia) Other/ungrouped * Immunoglobulin superfamily: AGM3, 6 * Integrin: LAD1 * Glanzmann's thrombasthenia * Junctional epidermolysis bullosa with pyloric atresia EDAR (EDAR hypohidrotic ectodermal dysplasia) * PTCH1 (Nevoid basal-cell carcinoma syndrome) * BMPR1A (BMPR1A juvenile polyposis syndrome) * IL2RG (X-linked severe combined immunodeficiency) See also cell surface receptors [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Thanatophoric dysplasia	c0039743	25,691	wikipedia	https://en.wikipedia.org/wiki/Thanatophoric_dysplasia	2021-01-18T18:49:42	{"gard": ["85"], "mesh": ["D013796"], "umls": ["C0039743"], "orphanet": ["1860", "2655", "93274", "93275"], "wikidata": ["Q1787020"]}
A rare, genetic macular disorder characterised by severe near-sightedness resulting from continual elongation of the eyeball. As the eyeball stretches the sclera and retina thin and the macula can tear, causing bleeding beneath the retina. It is a major cause of irreversible vision loss. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Myopic macular degeneration	c0730271	25,692	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=178493	2021-01-23T16:59:06	{"umls": ["C0730271"], "icd-10": ["H35.3"], "synonyms": ["Myopic maculopathy"]}
Mayaro virus disease is a mosquito-borne zoonotic pathogen endemic to certain humid forests of tropical South America. Infection with Mayaro virus causes an acute, self-limited dengue-like illness of 3–5 days' duration.[1] The causative virus, abbreviated MAYV, is in the family Togaviridae, and genus Alphavirus. It is closely related to other alphaviruses that produce a dengue-like illness accompanied by long-lasting arthralgia. It is only known to circulate in tropical South America.[1] ## Contents * 1 Virology * 2 Diagnosis * 3 Epidemiology * 4 Recent cases * 5 Treatment * 6 References ## Virology[edit] Mayaro virus Virus classification (unranked): Virus Realm: Riboviria Kingdom: Orthornavirae Phylum: Kitrinoviricota Class: Alsuviricetes Order: Martellivirales Family: Togaviridae Genus: Alphavirus Species: Mayaro virus Mayaro virus has a structure similar to other alphaviruses. It is an enveloped virus and has an icosahedral capsid with a diameter of 70 nm. The virus genome is composed of a linear, positive-sense, single-stranded RNA with 11,429 nucleotides, excluding the 5’ cap nucleotide and 3’ poly(A) tail.[2][3] The MAYV RNA genome contains the 5' untranslated region, 3' noncoding region, and two open reading frames (ORFs). The 5' proximal and 3' proximal ORFs are separated by a short, noncoding sequence and represent two-thirds and one-third of the genomic RNA, respectively. The 5’-proximal ORF codes for a polyprotein that after cleavage forms nonstructural proteins (nsP1, nsP2, nsP3, nsP4) and the 3’-proximal ORF with a 26S promoter codes for a polyprotein that is cleaved into structural proteins to generate capsid proteins and envelope surface glycoproteins (E1, E2, E3, C, 6K).[2][4][5][6] The nonstructural proteins (nsP) play different functions in the virus cycle. The nsP1 is an mRNA-capping enzyme, nsP2 has protease activity, and nsP4 is a RNA-direct RNA polymerase. The structural polyprotein is cleaved into six chains: capsid protein (C), p62, E3 protein or spike glycoprotein E3, E2 envelope glycoprotein or spike glycoprotein E2, 6K protein, and E1 envelope glycoprotein known also as spike glycoprotein E1.[7][8] The envelope lipid component is critical for virus particle stability and infectivity in mammalian cells[9] Once the virus enters into the host cell, the genomic RNA is released into the cytoplasm, where the two ORFs are translated into proteins and the synthesis of negative-stranded RNA starts. A consecutive synthesis of positive-stranded RNA takes place.[8] The MAYV sequences analysis showed two genotypes (D and L). The amplicon used for phylogenetic analysis includes E1 and E2 glycoprotein genes and the 3' NCR. The genotype D is distributed in Trinidad, Brazil, French Guyana, Surinam, Peru, and Bolivia, while the genotype L is limited to the north-central region of Brazil.[10] ## Diagnosis[edit] The MAYV infection is characterized by fever, headache, myalgia, rash, prominent pain in the large joints, and association with rheumatic disease,[11][12] but these signs and symptoms are unspecific to distinguish from other arboviruses. The MAYV infection can be confirmed by laboratory testing such as virus isolation, RT-PCR, and serology. The virus isolation in cell culture is effective during viremia. RT-PCR helps to identify virus. Serology tests detect antibodies like IgM and the most common assay is IgM-capture enzyme-linked immunosorbant assays (ELISA). This test usually requires a consecutive retest to confirm increasing titers.[13][14] While the IgG detection is applied for epidemiology studies.[15] ## Epidemiology[edit] The virus's transmission cycle in the wild is similar to the continuous sylvatic cycle of yellow fever, and is believed to involve wild primates (monkeys) as the natural reservoir and the tree canopy-dwelling Haemagogus species mosquito as the vector.[1] Human infections are strongly associated with exposure to humid tropical forest environments. Chikungunya virus is closely related, producing a nearly indistinguishable, highly debilitating arthralgic disease. On February 19, 2011, a Portuguese-language news source reported on a recent survey that revealed Mayaro virus activity in Manaus, Amazonas State, Brazil.[16] The survey studied blood samples from 600 residents of Manaus who had experienced a high fever; Mayaro virus was identified in 33 cases. Four of the cases experienced mild hemorrhagic (bleeding) symptoms, which had not previously been described in Mayaro virus disease. The report stated that this outbreak is the first detected in a metropolitan setting, and expressed concern that the disease might be adapting to urban species of mosquito vectors, which would make it a risk for spreading within the country. A study published in 1991 demonstrated that a colonized strain of Brazilian Aedes albopictus was capable of acquiring MAYV from infected hamsters and subsequently transmitting it,[17] and another study demonstrated that A. aegypti can transmit MAYV, supporting the possibility of wider transmission of Mayaro virus disease in urban settings.[18] A 2018 study demonstrated that A. aegypti and Culex quinquefasciatus were inefficient MAYV vectors, but Anopheles freeborni, Anopheles gambiae, Anopheles quadrimaculatus, and Anopheles stephensi were able to transmit MAYV, with three of the four capable of transmitting two genotypes.[19] The tested Anopheles species are native to Africa, Asia, and North America, suggesting that Anopheles spp. could play a significant role in the dissemination and establishment of MAYV in diverse regions of the world.[19] ## Recent cases[edit] An outbreak in Chuquisaca Department, Bolivia, involving 12 persons, was reported in May 2007.[20] In January 2010, a French tourist developed high-grade fever and severe joint pain manifestations following a 15-day trip in the Amazon basin, Brazil, and was diagnosed with MAYV infection in France. This case is the first reported in a traveler returning from an endemic South American country to Europe.[21] Mayaro virus disease has also been transported into the United States by two visitors infected in eastern Peru[22] and into the Netherlands by a couple infected while vacationing in Surinam.[23] The first outbreak of Mayaro virus disease in humans in Venezuela was reported in early June 2010, with 69 cases diagnosed in Ospino, Portuguesa state, and an additional two in San Fernando de Apure, Apure state, on 7 June 2010, for a total of 71 reported cases as of 8 June.[24] A virologist noted that the symptoms induced by Mayaro virus in the New World are atypical in the New World, supporting the theory that Mayaro virus is an Old World virus that was introduced to the New World, possibly via the slave trade.[citation needed] A single case of Mayaro virus in a child in Haiti in 2015 has been confirmed.[25] In 2019, cases were reported in Peru and Ecuador.[26] ## Treatment[edit] Research has suggested that macrophage migration inhibitory factor plays a critical role in determining the clinical severity of alphavirus-induced musculoskeletal disease and may provide a target for development of antiviral pharmaceuticals for Mayaro virus and other alphaviruses that affect human beings, such as Ross River virus, chikungunya, Sindbis virus, and O'nyong'nyong virus.[27] ## References[edit] 1. ^ a b c Receveur MC, Grandadam M, Pistone T, Malvy D (2010). "Infection with Mayaro virus in a French traveller returning from the Amazon region, Brazil, January, 2010". Euro Surveillance. 15 (18). PMID 20460093. 2. ^ a b Lavergne A, de Thoisy B, Lacoste V, Pascalis H, Pouliquen JF, Mercier V, Tolou H, Dussart P, Morvan J, Talarmin A, Kazanji M (2006). "Mayaro virus: complete nucleotide sequence and phylogenetic relationships with other alphaviruses". Virus Research. 117 (2): 283–90. doi:10.1016/j.virusres.2005.11.006. PMID 16343676. 3. ^ Mourão MP, Bastos Mde S, de Figueiredo RP, Gimaque JB, Galusso Edos S, Kramer VM, de Oliveira CM, Naveca FG, Figueiredo LT (2012). "Mayaro fever in the city of Manaus, Brazil, 2007-2008". Vector Borne and Zoonotic Diseases. 12 (1): 42–6. doi:10.1089/vbz.2011.0669. PMC 3249893. PMID 21923266. 4. ^ Snyder AJ, Mukhopadhyay S (2012). "The alphavirus E3 glycoprotein functions in a clade-specific manner". Journal of Virology. 86 (24): 13609–20. doi:10.1128/JVI.01805-12. PMC 3503070. PMID 23035234. 5. ^ Firth AE, Chung BY, Fleeton MN, Atkins JF (2008). "Discovery of frameshifting in Alphavirus 6K resolves a 20-year enigma". Virology Journal. 5: 108. doi:10.1186/1743-422X-5-108. PMC 2569925. PMID 18822126. 6. ^ Muñoz, Manuel; Navarro, Juan Carlos (2012). "Virus Mayaro: un arbovirus reemergente en Venezuela y Latinoamérica" [Mayaro virus: A re-emerging arboviruses in Venezuela and Latin America]. Biomédica. 32 (2). doi:10.7705/biomedica.v32i2.647. 7. ^ Netto M.C.M.G., Shirako Y., Strauss E.G., Carvalho M.G.C., Strauss J.H. Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases"Q8QZ73 (POLN_MAYAB)". 8. ^ a b Leung JY, Ng MM, Chu JJ (2011). "Replication of alphaviruses: a review on the entry process of alphaviruses into cells". Advances in Virology. 2011: 1–9. doi:10.1155/2011/249640. PMC 3265296. PMID 22312336. 9. ^ Sousa IP, Carvalho CA, Ferreira DF, Weissmüller G, Rocha GM, Silva JL, Gomes AM (2011). "Envelope lipid-packing as a critical factor for the biological activity and stability of alphavirus particles isolated from mammalian and mosquito cells". The Journal of Biological Chemistry. 286 (3): 1730–6. doi:10.1074/jbc.M110.198002. PMC 3023467. PMID 21075845. 10. ^ Powers AM, Aguilar PV, Chandler LJ, Brault AC, Meakins TA, Watts D, Russell KL, Olson J, Vasconcelos PF, Da Rosa AT, Weaver SC, Tesh RB (2006). "Genetic relationships among Mayaro and Una viruses suggest distinct patterns of transmission". The American Journal of Tropical Medicine and Hygiene. 75 (3): 461–9. doi:10.4269/ajtmh.2006.75.461. PMID 16968922. 11. ^ Figueiredo LT (2007). "Emergent arboviruses in Brazil". Revista da Sociedade Brasileira de Medicina Tropical. 40 (2): 224–9. doi:10.1590/S0037-86822007000200016. PMID 17568894. 12. ^ Suhrbier A, Jaffar-Bandjee MC, Gasque P (2012). "Arthritogenic alphaviruses--an overview". Nature Reviews. Rheumatology. 8 (7): 420–9. doi:10.1038/nrrheum.2012.64. PMID 22565316. 13. ^ Forshey BM, Guevara C, Laguna-Torres VA, Cespedes M, Vargas J, Gianella A, Vallejo E, Madrid C, Aguayo N, Gotuzzo E, Suarez V, Morales AM, Beingolea L, Reyes N, Perez J, Negrete M, Rocha C, Morrison AC, Russell KL, Blair PJ, Olson JG, Kochel TJ (2010). "Arboviral etiologies of acute febrile illnesses in Western South America, 2000-2007". PLOS Neglected Tropical Diseases. 4 (8): e787. doi:10.1371/journal.pntd.0000787. PMC 2919378. PMID 20706628. 14. ^ Wang E, Paessler S, Aguilar PV, Carrara AS, Ni H, Greene IP, Weaver SC (2006). "Reverse transcription-PCR-enzyme-linked immunosorbent assay for rapid detection and differentiation of alphavirus infections". Journal of Clinical Microbiology. 44 (11): 4000–8. doi:10.1128/JCM.00175-06. PMC 1698312. PMID 16957044. 15. ^ Abad-Franch F, Grimmer GH, de Paula VS, Figueiredo LT, Braga WS, Luz SL (2012). "Mayaro virus infection in amazonia: a multimodel inference approach to risk factor assessment". PLOS Neglected Tropical Diseases. 6 (10): e1846. doi:10.1371/journal.pntd.0001846. PMC 3469468. PMID 23071852. 16. ^ "Manaus tem surto de vírus semelhante ao da dengue" [Manaus has virus outbreak similar to dengue]. Folha de S. Paulo. February 19, 2011. 17. ^ Smith GC, Francy DB (1991). "Laboratory studies of a Brazilian strain of Aedes albopictus as a potential vector of Mayaro and Oropouche viruses". Journal of the American Mosquito Control Association. 7 (1): 89–93. PMID 1646286. 18. ^ Long KC, Ziegler SA, Thangamani S, Hausser NL, Kochel TJ, Higgs S, Tesh RB (October 2011). "Experimental transmission of Mayaro virus by Aedes aegypti". The American Journal of Tropical Medicine and Hygiene. 85 (4): 750–7. doi:10.4269/ajtmh.2011.11-0359. PMC 3183788. PMID 21976583. 19. ^ a b Marco Brustolin, Sujit Pujhari, Cory A. Henderson, and Jason L. Rasgon. 2018. Anopheles mosquitoes may drive invasion and transmission of Mayaro virus across geographically diverse regions. PLOS Neglected Tropical Diseases 12(11): e0006895, https://doi.org/10.1371/journal.pntd.0006895, last accessed 30 Nov 2018. 20. ^ "Seis regiones de Bolivia afectadas por brote de epidemias tras las lluvias" [Six regions of Bolivia affected by outbreak of epidemics after rains]. Terra. May 13, 2007. Archived from the original on July 9, 2009. 21. ^ Young, Alison (March 31, 2016). "Latest CDC lab incident involves worker infected with salmonella". USA Today. 22. ^ Tesh RB, Watts DM, Russell KL, Damodaran C, Calampa C, Cabezas C, Ramirez G, Vasquez B, Hayes CG, Rossi CA, Powers AM, Hice CL, Chandler LJ, Cropp BC, Karabatsos N, Roehrig JT, Gubler DJ (1999). "Mayaro virus disease: an emerging mosquito-borne zoonosis in tropical South America". Clinical Infectious Diseases. 28 (1): 67–73. doi:10.1086/515070. PMID 10028074. 23. ^ Hassing RJ, Leparc-Goffart I, Blank SN, Thevarayan S, Tolou H, van Doornum G, van Genderen PJ (2010). "Imported Mayaro virus infection in the Netherlands". The Journal of Infection. 61 (4): 343–5. doi:10.1016/j.jinf.2010.06.009. PMID 20600300. 24. ^ Chiappe, Giuliana (June 7, 2010). "Detectan dos casos más de fiebre mayaro en Apure" [Two more cases of Mayaro fever detected in Apure]. El Universal. Archived from the original on August 8, 2014. 25. ^ Lednicky, John; De Rochars, Valery Madsen Beau; Elbadry, Maha; Loeb, Julia; Telisma, Taina; Chavannes, Sonese; Anilis, Gina; Cella, Eleonora; Ciccozzi, Massimo; Okech, Bernard; Salemi, Marco; Morris, J. Glenn (2016). "Mayaro Virus in Child with Acute Febrile Illness, Haiti, 2015". Emerging Infectious Diseases. 22 (11): 2000–2002. doi:10.3201/eid2211.161015. ISSN 1080-6040. PMC 5088037. PMID 27767924. 26. ^ https://www.paho.org/hq/index.php?option=com_docman&view=download&category_slug=mayaro-fever-2323&alias=48374-1-may-2019-mayaro-fever-epidemiological-alert&Itemid=270&lang=en 27. ^ Herrero LJ, Nelson M, Srikiatkhachorn A, Gu R, Anantapreecha S, Fingerle-Rowson G, Bucala R, Morand E, Santos LL, Mahalingam S (2011). "Critical role for macrophage migration inhibitory factor (MIF) in Ross River virus-induced arthritis and myositis". Proceedings of the National Academy of Sciences of the United States of America. 108 (29): 12048–53. Bibcode:2011PNAS..10812048H. doi:10.1073/pnas.1101089108. JSTOR 27978946. PMC 3141998. 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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 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Mayaro virus disease	None	25,693	wikipedia	https://en.wikipedia.org/wiki/Mayaro_virus_disease	2021-01-18T18:40:38	{"wikidata": ["Q3073143"]}
A rare urogenital tumor characterized by origin from squamous epithelial cells of the penis, most commonly the glans or inner surface of the prepuce. Macroscopically, the tumors can appear either papillary or flat and ulcerating. Histological subtypes include usual squamous cell carcinoma as the most common type, as well as basaloid, warty, verrucous, papillary, and mixed carcinomas. Patients may initially be asymptomatic but present with itching, bleeding, discharge, foul odor, and pain, as the disease progresses. Regional lymph node involvement is common, while distant metastases occur only late in the disease. Risk factors include HPV infection, smoking, poor hygiene, and HIV infection. Neonatal circumcision is implicated as strongly protective. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Squamous cell carcinoma of the penis	c0238348	25,694	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=398058	2021-01-23T17:15:31	{"umls": ["C0238348"], "icd-10": ["C60.0", "C60.1", "C60.2", "C60.8", "C60.9"], "synonyms": ["Penile squamous cell carcinoma"]}
Spinal lipomas are the most common form of occult spinal dysraphism and include lipomyelomeningoceles. The familial occurrence of lipomyelomeningocele was reported by Seeds and Powers (1988). Kannu et al. (2005) described a family in which 2 successively born sibs were affected by lipomyelomeningocele. The parents were nonconsanguineous. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	LIPOMYELOMENINGOCELE	c1836022	25,695	omim	https://www.omim.org/entry/609537	2019-09-22T16:05:53	{"mesh": ["C537030"], "omim": ["609537"]}
## Summary ### Clinical characteristics. If untreated, young children with profound biotinidase deficiency usually exhibit neurologic abnormalities including seizures, hypotonia, ataxia, developmental delay, vision problems, hearing loss, and cutaneous abnormalities (e.g., alopecia, skin rash, candidiasis). Older children and adolescents with profound biotinidase deficiency often exhibit motor limb weakness, spastic paresis, and decreased visual acuity. Once vision problems, hearing loss, and developmental delay occur, they are usually irreversible, even with biotin therapy. Individuals with partial biotinidase deficiency may have hypotonia, skin rash, and hair loss, particularly during times of stress. ### Diagnosis/testing. The diagnosis of biotinidase deficiency is established in a proband whose newborn screening or biochemical findings indicate multiple carboxylase deficiency based on either detection of deficient biotinidase enzyme activity in serum/plasma OR identification of biallelic pathogenic variants in BTD on molecular genetic testing. ### Management. Treatment of manifestations: All symptomatic children with profound biotinidase deficiency improve when treated with 5-10 mg of oral biotin per day. All individuals with profound biotinidase deficiency, even those who have some residual enzymatic activity, should have lifelong treatment with biotin. Children with vision problems may benefit from vision aids; those with hearing loss will usually benefit from hearing aids or cochlear implants, and those with developmental deficits from appropriate interventions. Prevention of primary manifestations: Children with biotinidase deficiency identified by newborn screening should remain asymptomatic if biotin therapy is instituted early and continuously lifelong. Surveillance: Annual vision and hearing evaluation, physical examination, and periodic assessment by a metabolic specialist. Agents/circumstances to avoid: Raw eggs because they contain avidin, an egg-white protein that binds biotin and decreases the bioavailability of the vitamin. Evaluation of relatives at risk: Testing of asymptomatic sibs of a proband ensures that biotin therapy for affected sibs can be instituted in a timely manner. ### Genetic counseling. Biotinidase deficiency is inherited in an autosomal recessive manner. With each pregnancy, a couple who has had one affected child has a 25% chance of having an affected child, a 50% chance of having a child who is an asymptomatic carrier, and a 25% chance of having an unaffected child who is not a carrier. Carrier testing for at-risk family members and prenatal testing for pregnancies at increased risk are options if the pathogenic variants in the family are known. ## Diagnosis Clinical issues and frequently asked questions regarding biotinidase deficiency have been addressed in a review [Wolf 2010]. ### Suggestive Findings Biotinidase deficiency should be suspected in infants with positive newborn screening results, untreated individuals with clinical findings, and persons with suggestive preliminary laboratory findings [Wolf 2012]: #### Positive Newborn Screening Results Virtually 100% of infants with either profound biotinidase deficiency or partial biotinidase deficiency can be detected in the US by newborn screening (see Baby's First Test for state-by-state screening information). Newborn screening utilizes a small amount of blood obtained from a heel prick for a colorimetric test for biotinidase activity: * False positive test results may occur in premature infants and in samples placed in plastic prior to sufficient drying. * Measurement of biotinidase enzyme activity in serum/plasma is warranted in infants whose initial screening tests are abnormal. #### Clinical Findings Children or adults with untreated profound biotinidase deficiency usually exhibit one or more of the following nonspecific features (which are also observed in many other inherited metabolic disorders): * Seizures * Hypotonia * Respiratory problems including hyperventilation, laryngeal stridor, and apnea * Developmental delay * Hearing loss * Vision problems, such as optic atrophy Features more specific to profound biotinidase deficiency include the following: * Eczematous skin rash * Alopecia * Conjunctivitis * Candidiasis * Ataxia Older children and adolescents may exhibit limb weakness, paresis, and scotomata. Some have exhibited findings suggestive of a myelopathy and have been initially incorrectly diagnosed and treated as having another disorder before biotinidase deficiency is correctly diagnosed [Wolf 2015]. Children or adults with untreated partial biotinidase deficiency may exhibit any of the above signs and symptoms, but the manifestations are mild and occur only when the person is stressed, such as with a prolonged infection. #### Preliminary Laboratory Findings The following findings are suggestive of biotinidase deficiency: * Metabolic ketolactic acidosis * Organic aciduria (usually with the metabolites commonly seen in multiple carboxylase deficiency; however, 3-hydroxyisovalerate may be the only metabolite present). Note: Urinary organic acids can be normal even in individuals with biotinidase deficiency who are symptomatic. * Hyperammonemia ### Establishing the Diagnosis The diagnosis of biotinidase deficiency is established in a proband whose newborn screening or biochemical findings indicate multiple carboxylase deficiency based on EITHER of the following: * Detection of deficient biotinidase enzyme activity in serum/plasma * Identification of biallelic pathogenic variants in BTD on molecular genetic testing (Table 1) when the results of enzymatic testing are ambiguous (e.g., in differentiating profound biotinidase deficiency from partial biotinidase deficiency and in differentiating heterozygosity for profound biotinidase deficiency from partial biotinidase deficiency) Biotinidase enzyme activity in serum. The working group of the American College of Medical Genetics Laboratory Quality Assurance Committee has established technical standards and guidelines for the diagnosis of biotinidase deficiency [Cowan et al 2010] (full text). * Profound biotinidase deficiency: <10% mean normal serum biotinidase activity * Partial biotinidase deficiency: 10%-30% of mean normal serum biotinidase activity Note: (1) With appropriate controls, biochemical testing is definitive for confirming the diagnosis. It is important that a normal unrelated control sample and samples from the parent(s) accompany the serum/plasma sample from the proband to the diagnostic laboratory for accurate interpretation of enzymatic results [Neto et al 2004]. (2) An increasing problem of enzymatic deterioration (false positives) is almost certainly the result of inadequate storage of samples either prior to shipping to commercial laboratories or at some laboratories [Wolf 2003]. Molecular genetic testing is performed by single-gene testing. Sequence analysis of BTD is performed first, followed by gene-targeted deletion/duplication analysis if only one or no pathogenic variant is found. ### Table 1. Molecular Genetic Testing Used in Biotinidase Deficiency View in own window Gene 1MethodProportion of Probands with Pathogenic Variants 2 Detectable by Method BTDSequence analysis 3~99% 4 Gene-targeted deletion/duplication analysis 5See footnote 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\. Almost all individuals with partial biotinidase deficiency have the pathogenic variant p.Asp444His in one allele of BTD in combination with a pathogenic variant for profound deficiency in the other allele [Swango et al 1998]. 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\. Two large BTD deletions have been reported in affected individuals [Senanayake et al 2015, Wolf 2016]. ## Clinical Characteristics ### Clinical Description Individuals with biotinidase deficiency who are diagnosed before they have developed symptoms (e.g., by newborn screening) and who are treated with biotin have normal development [Möslinger et al 2001, Weber et al 2004] (see also Management, Prevention of Primary Manifestations). Neurologic problems occur only in those individuals with biotinidase deficiency who have recurrent symptoms and metabolic compromise prior to biotin treatment. #### Profound Biotinidase Deficiency Early onset. Symptoms of untreated profound biotinidase deficiency (<10% mean normal serum biotinidase activity) usually appear between ages one week and ten years, with a mean age of three and one-half months [Wolf et al 1985b]. Some children with biotinidase deficiency manifest only a single finding, whereas others exhibit multiple neurologic and cutaneous findings. The most common neurologic features in individuals with untreated, profound biotinidase deficiency are seizures and hypotonia [Wolf et al 1983a, Wolf et al 1985b, Wastell et al 1988, Wolf 1995, Wolf 2011]. The seizures are usually myoclonic but may be grand mal and focal; some children have infantile spasms [Salbert et al 1993b]. Some untreated children have exhibited spinal cord involvement characterized by progressive spastic paresis and myelopathy [Chedrawi et al 2008]. Older affected children often have ataxia and developmental delay. Many symptomatic children with biotinidase deficiency exhibit a variety of central nervous system abnormalities on brain MRI or CT [Wolf et al 1983b, Wastell et al 1988, Lott et al 1993, Salbert et al 1993b, Grünewald et al 2004]. These findings may improve or become normal after biotin treatment. Sensorineural hearing loss and eye problems (e.g., optic atrophy) have also been described in untreated children [Wolf et al 1983b, Taitz et al 1985, Salbert et al 1993a, Weber et al 2004]. Approximately 76% of untreated symptomatic children with profound biotinidase deficiency have sensorineural hearing loss that usually does not resolve or improve but remains static with biotin treatment [Wolf et al 2002]. Cutaneous manifestations include skin rash, alopecia, and recurrent viral or fungal infections caused by immunologic dysfunction. Respiratory problems including hyperventilation, laryngeal stridor, and apnea can occur. One death initially thought to be caused by sudden infant death syndrome was subsequently attributed to biotinidase deficiency [Burton et al 1987]. Late onset. A number of children with profound biotinidase deficiency were asymptomatic until adolescence, when they developed sudden loss of vision with progressive optic neuropathy and spastic paraparesis [Ramaekers et al 1992, Lott et al 1993, Ramaekers et al 1993]. After several months of biotin therapy, the eye findings resolved and the spastic paraparesis improved. In other individuals with enzyme deficiency, paresis and eye problems have occurred during early adolescence [Tokatli et al 1997, Wolf et al 1998, Wolf 2015]. #### Partial Biotinidase Deficiency Individuals with partial biotinidase deficiency (10%-30% of mean normal serum biotinidase activity) may develop symptoms only when stressed, such as during infection. One child with partial biotinidase deficiency who was not treated with biotin exhibited hypotonia, skin rash, and hair loss during an episode of gastroenteritis at approximately age six months. When treated with biotin, the symptoms resolved. ### Genotype-Phenotype Correlations Genotype/phenotype correlations are not well established. Deletions, insertions, or nonsense variants usually result in complete absence of biotinidase enzyme activity, whereas missense variants may or may not result in complete loss of biotinidase enzyme activity. Those with absence of all biotinidase enzyme activity are likely to be at increased risk for earlier onset of symptoms. Although genotype-phenotype correlations are not well established, in one study, children with symptoms of profound biotinidase deficiency with null variants were more likely to develop hearing loss than those with missense variants, even if not treated for a period of time [Sivri et al 2007]. Certain genotypes correlate with complete biotinidase deficiency and others with partial biotinidase deficiency. Profound biotinidase deficiency (<10% mean normal serum biotinidase activity): * Most BTD pathogenic variants cause complete loss or near-complete loss of biotinidase enzyme activity. These alleles are considered profound biotinidase deficiency alleles; a combination of two such alleles, whether homozygous or compound heterozygous, results in profound biotinidase deficiency. Affected individuals are likely to develop symptoms if not treated with biotin. * Several adults with profound biotinidase deficiency have never had symptoms and have never been treated [Wolf et al 1997] whereas some children with the same pathogenic variants have been symptomatic. Therefore, it has been speculated that some children with profound biotinidase deficiency may exhibit mild or no symptoms if left untreated. Nonetheless, it is recommended that such children be treated [Möslinger et al 2003]. Partial biotinidase deficiency (10%-30% of mean normal serum biotinidase activity) * Compound heterozygotes for the p.Asp444His pathogenic variant and a pathogenic variant that results in profound biotinidase deficiency are expected to have approximately 20%-25% of mean normal serum biotinidase enzyme activity [Swango et al 1998]. Heterozygotes * Individuals with one profound or one partial biotinidase deficiency BTD variant are carriers of biotinidase deficiency and do not exhibit symptoms [B Wolf, personal observation]. Such individuals do not require biotin therapy. * Individuals who are homozygous for the p.Asp444His pathogenic variant are expected to have approximately 45%-50% of mean normal serum biotinidase enzyme activity (which is similar to the activity of heterozygotes for profound biotinidase deficiency) and do not require biotin therapy. ### Penetrance Almost all children with profound biotinidase deficiency become symptomatic or are at risk of becoming symptomatic if not treated. Several reports describe adults with profound biotinidase deficiency who have offspring who also have profound biotinidase deficiency identified by newborn screening, but who have never had symptoms [Wolf et al 1997, Baykal et al 2005]. In addition, several enzyme-deficient sibs of symptomatic children have apparently never exhibited symptoms. It is possible that these individuals would become symptomatic if stressed, such as with a prolonged infection. ### Nomenclature Profound and partial biotinidase deficiency is the accepted nomenclature for this disorder. Individuals with partial biotinidase deficiency were previously described as having late-onset or juvenile multiple or combined carboxylase deficiency. Biotinidase deficiency should not be confused with holocarboxylase synthetase deficiency (see Differential Diagnosis), previously referred to as early-onset or infantile multiple or combined carboxylase deficiency. ### Prevalence Based on the results of worldwide screening of biotinidase deficiency [Wolf 1991], the incidence of the disorder is: * One in 137,401 for profound biotinidase deficiency; * One in 109,921 for partial biotinidase deficiency; * One in 61,067 for the combined incidence of profound and partial biotinidase deficiency. The incidence of biotinidase deficiency is generally higher in populations with a high rate of consanguinity (e.g., Turkey, Saudi Arabia). The incidence appears to be increased in the Hispanic population [Cowan et al 2012] and it may be lower in the African American population. Carrier frequency in the general population is approximately one in 120. ## Differential Diagnosis Clinical features including vomiting, hypotonia, and seizures accompanied by metabolic ketolactic acidosis or mild hyperammonemia are often observed in inherited metabolic diseases. Individuals with biotinidase deficiency may exhibit clinical features that are misdiagnosed as other disorders (e.g., isolated carboxylase deficiency) before they are correctly identified [Suormala et al 1985, Wolf & Heard 1989]. Other symptoms that are more characteristic of biotinidase deficiency (e.g., skin rash, alopecia) can also occur in children with nutritional biotin deficiency, holocarboxylase synthetase deficiency, zinc deficiency, or essential fatty acid deficiency. See Figure 1. #### Figure 1. The biotin cycle Free biotin enters the cycle from dietary sources or from the cleavage of biocytin or biotinyl-peptides by the action of biotinidase. The free biotin is then covalently attached to the various apocarboxylases, propionyl-CoA carboxylase (more...) Biotin deficiency. Biotin deficiency can usually be diagnosed by dietary history. Individuals with biotin deficiency may have a diet containing raw eggs or protracted parenteral hyperalimentation without biotin supplementation. Low-serum biotin concentrations are useful in differentiating biotin and biotinidase deficiencies from holocarboxylase synthetase deficiency; however, it is important to know the method used for determining the biotin concentration as only methods that distinguish biotin from biocytin or bound biotin yield reliable estimates of free biotin concentrations. Isolated carboxylase deficiency. Urinary organic acid analysis is useful for differentiating isolated carboxylase deficiencies from the multiple carboxylase deficiencies that occur in biotinidase deficiency and holocarboxylase synthetase deficiency: * Beta-hydroxyisovalerate is the most commonly elevated urinary metabolite in biotinidase deficiency, holocarboxylase synthetase deficiency (OMIM 253270), isolated beta-methylcrotonyl-CoA carboxylase deficiency (OMIM PS210220), and acquired biotin deficiency. * In addition to beta-hydroxyisovalerate, elevated concentrations of urinary lactate, methylcitrate, and beta-hydroxypropionate are indicative of the multiple carboxylase deficiencies, including the above disorders and propionic acidemia and pyruvate carboxylase deficiency. The multiple carboxylase deficiencies are biotin responsive, whereas the isolated carboxylase deficiencies are not. A trial of biotin can be useful for discriminating between the disorders. Isolated carboxylase deficiency can be diagnosed by demonstrating deficient enzyme activity of one of the three mitochondrial carboxylases in peripheral blood leukocytes (prior to biotin therapy) or in cultured fibroblasts grown in low biotin-containing medium, and normal activity of the other two carboxylases. Holocarboxylase synthetase deficiency (OMIM 253270). Both biotinidase deficiency and holocarboxylase synthetase deficiency are characterized by deficient activities of the three mitochondrial carboxylases in peripheral blood leukocytes prior to biotin treatment. In both disorders, these activities increase to near-normal or normal after biotin treatment. The symptoms of biotinidase deficiency and holocarboxylase synthetase deficiency are similar, and clinical differentiation is often difficult. The age of onset of symptoms may be useful for distinguishing between holocarboxylase synthetase deficiency and biotinidase deficiency. Holocarboxylase synthetase deficiency usually presents with symptoms before age three months, whereas biotinidase deficiency usually presents after age three months; however, there are exceptions for both disorders. Organic acid abnormalities in biotinidase deficiency and holocarboxylase synthetase deficiency are similar and may be reported as consistent with multiple carboxylase deficiency. However, the tandem mass spectroscopic methodology that is being incorporated into many newborn screening programs should identify metabolites that are consistent with multiple carboxylase deficiency. Because most children with holocarboxylase synthetase deficiency excrete these metabolites in the newborn period, the disorder should be identifiable using this technology. Definitive enzyme determinations are required to distinguish between the two disorders: * Biotinidase enzyme activity is normal in serum of individuals with holocarboxylase synthetase deficiency; therefore, the enzymatic assay of biotinidase activity used in newborn screening is specific for biotinidase deficiency and does not identify children with holocarboxylase synthetase deficiency. * Individuals with holocarboxylase synthetase deficiency have deficient activities of the three mitochondrial carboxylases in extracts of fibroblasts that are incubated in medium containing only the biotin contributed by fetal calf serum (low biotin), whereas individuals with biotinidase deficiency have normal carboxylase activities in fibroblasts. The activities of the carboxylases in fibroblasts of individuals with holocarboxylase synthetase deficiency become near-normal to normal when cultured in medium supplemented with biotin (high biotin). Sensorineural hearing loss (see Deafness and Hereditary Hearing Loss Overview). Sensorineural hearing loss has many causes. Biotinidase deficiency can be excluded as a cause by determining biotinidase enzyme activity in serum. This test should be performed specifically on children with hearing loss who are exhibiting other clinical features consistent with biotinidase deficiency. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in a symptomatic individual diagnosed with biotinidase deficiency, the following evaluations are recommended: * History of seizures, balance problems, feeding problems, breathing problems, loss of hair, fungal infections, skin rash, conjunctivitis * Physical examination for hypotonia, ataxia, eye findings such as optic atrophy, eczematous skin rash, alopecia, conjunctivitis, breathing abnormalities such as stridor, thrush, and/or candidiasis * Evaluation for psychomotor deficits * Evaluation for sensorineural hearing loss * Ophthalmologic examination * Identification of cellular immunologic abnormalities because of the increased risk of recurrent viral or fungal infections caused by immunologic dysfunction * Consultation with a metabolic specialist or clinical geneticist To establish the extent of disease and needs in infants or children diagnosed with biotinidase deficiency following newborn screening, the following evaluations are recommended: * Physical examination for neurologic findings (e.g., hypotonia, ataxia), eye findings (e.g., conjunctivitis), skin findings (eczematous rash, alopecia), breathing abnormalities (e.g., stridor) and fungal infections caused by immunologic dysfunction (thrush and/or candidiasis). * Evaluation for psychomotor deficits * Evaluation for sensorineural hearing loss * Ophthalmologic examination (for finding such as optic atrophy) * Consultation with a metabolic specialist or clinical geneticist ### Treatment of Manifestations Although newborn screening for biotinidase deficiency has resulted in almost complete ascertainment of children with biotinidase deficiency in the United States and in many other countries, occasionally a child who has not been screened or has been mistakenly thought to have normal biotinidase activity on newborn screening will present with clinical symptoms. These children may become metabolically compromised and require hydration, occasionally bicarbonate for acidosis, and procedures to ameliorate hyperammonemia. Once it is recognized that the child has a multiple carboxylase deficiency, administration of biotin – or a multivitamin "cocktail" containing biotin – can rapidly resolve the metabolic derangement and improve many of the clinical symptoms within hours to days. Compliance with biotin therapy (see Prevention of Primary Manifestations) improves symptoms in symptomatic individuals. Some features such as optic atrophy, hearing loss, or developmental delay may not be reversible; they should be addressed with ophthalmologic evaluations and intervention, hearing aids or cochlear implants, and appropriate interventions for developmental deficits. ### Prevention of Primary Manifestations All individuals with profound biotinidase deficiency (<10% mean normal enzyme activity), even those who have some residual biotinidase enzyme activity, should be treated with biotin independent of their genotype [Wolf 2003]. Note: Although Möslinger et al [2003] stated that children with greater than 1% to 10% biotinidase activity may not need treatment, a child with 1% to 10% biotinidase activity may be just as likely to develop symptoms as one with total loss of enzyme activity [Wolf 2002]. It is therefore strongly recommended that all children with profound biotinidase deficiency, regardless of the residual biotinidase enzyme activity, be treated with biotin. Note: Because genotype/phenotype correlations in biotinidase deficiency are not well established, decisions regarding treatment should be based on the results of enzyme activity rather than molecular genetic testing. Biotinidase deficiency is treated by supplementation with oral biotin in free form as opposed to the bound form. Children with biotinidase deficiency identified by newborn screening will remain asymptomatic with compliance to biotin therapy. All symptomatic children with biotinidase deficiency have improved after treatment with 5-10 mg oral biotin per day. Biotin is usually dispensed as a tablet or a capsule (most of which is filler: the quantity of biotin is minute relative to the quantity of filler). To administer biotin to an infant or young child, the tablet can be crushed or the contents of the capsule can be mixed with breast milk or formula in a spoon, medicine dispenser, or syringe. Note that the contents of the tablet or capsule should not be put into a bottle because the mixture will stick to the bottle and/or fail to pass through the nipple, thus delivering inconsistent doses. Although biotin occasionally is dispensed as a solution or syrup, these liquid preparations are not recommended because the mixture – which is a suspension – tends to settle (especially upon refrigeration) and to grow bacteria upon storage. The liquid preparations usually do not provide a consistent dose and should not be added to milk in a bottle. The biochemical abnormalities and seizures rapidly resolve after biotin treatment, followed by improvement of the cutaneous abnormalities. Hair growth returns over a period of weeks to months in children who have alopecia. Optic atrophy and hearing loss may be resistant to therapy, especially if a long period has elapsed between their onset and the initiation of treatment. Some treated children have rapidly achieved developmental milestones, whereas others have continued to show delays. Only a few anecdotal reports exist regarding symptoms in children with partial biotinidase deficiency who were not treated with biotin. Because there is no known toxicity for biotin, children with partial deficiency are usually treated with 1-10 mg oral biotin per day. Biotin therapy is lifelong. There are no known adverse side effects from pharmacologic doses of biotin. In fact, the major problem is the lack of treatment or non-compliance with prescribed treatment. More data are required to determine the dosage of biotin that is necessary for older children with either profound or partial biotinidase deficiency, but essentially all children have tolerated 10 mg/day of oral biotin with no side effects. Anecdotally, two girls with profound biotinidase deficiency developed hair loss during adolescence that resolved following increase of their biotin dosages from 10 mg per day to 15 or 20 mg per day. A protein-restricted diet is not necessary. ### Surveillance For all children with biotinidase deficiency: * Yearly ophthalmologic examination and auditory testing for individuals with profound deficiency and every two years for those with partial deficiency * Regularly scheduled appointments with primary care physicians or as needed * Yearly evaluation by a clinical geneticist or metabolic specialist for individuals with profound deficiency and every two years for those with partial deficiency Symptomatic children with residual clinical problems should be seen as directed by the appropriate sub-specialists: * Evaluation of urinary organic acids if return of symptoms with biotin therapy (most commonly the result of non-compliance) Note: Measurement of biotin concentrations in blood or urine is not useful except to determine compliance with therapy. ### Agents/Circumstances to Avoid Raw eggs should be avoided because they contain avidin, an egg-white protein that binds biotin, thus decreasing its bioavailability. (Thoroughly cooked eggs present no problem because heating inactivates avidin, rendering it incapable of binding biotin.) ### Evaluation of Relatives at Risk A newborn with an older sib with biotinidase deficiency should be treated at birth with biotin pending results of the definitive biotinidase enzyme activity assay and/or molecular genetic testing (if the BTD pathogenic variants in the family are known). The genetic status of older sibs (even if asymptomatic) of a child with biotinidase deficiency should be clarified by assay of biotinidase enzyme activity or molecular genetic testing (if the BTD pathogenic variants in the family are known) so that biotin therapy can be instituted in a timely manner. The genetic status of any relative with symptoms consistent with biotinidase deficiency should be clarified by assay of biotinidase enzyme activity or molecular genetic testing (if the BTD pathogenic variants in the family are known) so that biotin therapy can be instituted in a timely manner. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management The only special pregnancy management considerations for a woman who is carrying a baby with biotinidase deficiency or is at risk of having a baby with biotinidase deficiency is consideration of biotin supplementation of the mother. An optimal prenatal dose has not been determined. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Biotinidase Deficiency	c0220754	25,696	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1322/	2021-01-18T21:39:53	{"mesh": ["D028921"], "synonyms": ["Late-Onset Multiple Carboxylase Deficiency"]}
A number sign (#) is used with this entry because nephronophthisis-18 (NPHP18) is caused by homozygous or compound heterozygous mutation in the CEP83 gene (615847) on chromosome 12q22. Description Nephronophthisis-18 is an autosomal recessive disorder characterized by chronic tubulointerstitial nephritis resulting in end-stage renal disease in early childhood. Extrarenal manifestations, including intellectual disability or liver changes, may occur in some patients (summary by Failler et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of nephronophthisis, see NPHP1 (256100). Clinical Features Failler et al. (2014) reported 8 children from 7 families with early-onset nephronophthisis resulting in end-stage renal disease between 1 and 4 years of age. Four patients also had neurologic problems, including speech delay, intellectual disability, and/or hydrocephalus. One patient had retinitis, another had strabismus, and 2 had liver changes, including hepatic cytolysis, cholestasis, and portal septal fibrosis. Renal biopsies showed 2 types of histologic patterns: microcystic tubular dilatations associated with tubular atrophy and interstitial fibrosis, and atrophic tubules with thickening of the basement membranes and massive interstitial fibrosis. Two patients had hypertension. Inheritance The transmission pattern of NPHP18 in the families reported by Failler et al. (2014) was consistent with autosomal recessive inheritance. Molecular Genetics In 8 patients from 7 families with nephronophthisis, Failler et al. (2014) identified homozygous or compound heterozygous mutations in the CEP83 gene (see, e.g., 615847.0001-615847.0007). The initial mutations were found by analyzing a cohort of 1,255 individuals with NPHP-related ciliopathies by applying exon-enriched targeting of up to 1,221 genes associated with cilia and 5 known distal appendage (DAP)-encoding genes. Seven of the patients carried a missense mutation or in-frame deletion on at least 1 allele, suggesting that some protein function may have been preserved in these patients. One patient with a more severe phenotype and multiple organ involvement was homozygous for a truncating mutation. Fibroblasts and tubular renal cells from 2 patients were consistent with altered DAP composition and assembly. Transfection studies of individual mutations in retinal epithelial cells showed that some of the mutations resulted in normal CEP83 localization but exerted a dominant-negative effect on CEP164 localization, whereas others resulted in CEP83 accumulation in the nucleus and failure to localize at the centrosome. Fibroblasts from 2 patients showed defects in ciliogenesis. INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Retinitis (in some patients) \- Strabismus (in some patients) CARDIOVASCULAR Vascular \- Hypertension due to renal disease ABDOMEN Liver \- Hepatic involvement (in some patients) \- Cholestasis (in some patients) \- Hepatic cytolysis (in some patients) \- Portal fibrosis (in some patients) GENITOURINARY Kidneys \- Nephronophthisis \- Tubulointerstitial nephritis \- Microcystic tubular dilatations \- Corticomedullary cysts \- Tubular atrophy \- Thickening of the glomerular basement membrane \- End-stage renal disease NEUROLOGIC Central Nervous System \- Intellectual disability (in some patients) \- Hydrocephalus (in some patients) MISCELLANEOUS \- Onset in early childhood \- About 50% of patients have intellectual disability and/or hydrocephalus MOLECULAR BASIS \- Caused by mutation in the 83-kD centrosomal protein gene (CEP83, 615847.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	NEPHRONOPHTHISIS 18	c0687120	25,697	omim	https://www.omim.org/entry/615862	2019-09-22T15:50:49	{"doid": ["0111125"], "omim": ["615862"], "orphanet": ["655"], "genereviews": ["NBK368475"]}
Herpetophobia SpecialtyPsychology Herpetophobia [1] is a common specific phobia, which consists of fear or aversion to reptiles, commonly lizards and snakes, and similar vertebrates as amphibians. It is one of the most diffused [2] animal phobias, very similar and related to ophidiophobia. This condition causes a slight to severe emotional reaction, as for example anxiety, panic attack or most commonly nausea.[3] ## See also[edit] * Zoophobia * Ophidiophobia * List of animal phobias ## References[edit] 1. ^ "Definition of Herpetophobia on Merriam-Webster Medical Dictionary". Archived from the original on 2011-05-26. Retrieved 2009-07-28. 2. ^ Herpetophobia on phobias.about.com 3. ^ Herpetophobia on wrongdiagnosis.com ## External links[edit] The dictionary definition of herpetophobia at Wiktionary This abnormal psychology–related article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Herpetophobia	None	25,698	wikipedia	https://en.wikipedia.org/wiki/Herpetophobia	2021-01-18T18:38:13	{"wikidata": ["Q2319444"]}
A number of studies have demonstrated adverse reactions in pets after administering vaccines to both dogs[1] and cats.[2] Concern about adverse effects has led to revised guidelines that alter the recommended frequency and methods/locations for both vaccination of dogs and feline vaccination. ## Contents * 1 Controversy * 2 Possible causes * 2.1 Vaccine-specific * 2.2 Animal-specific * 3 Types of reactions * 3.1 Ischemic Dermatopathy / Cutaneous Vasculitis * 3.2 Urticaria / Anaphylaxis * 3.3 Development of antibodies against kidney tissue * 3.4 Sarcoma / Tumor * 4 Recommendations * 4.1 Location * 4.2 Frequency and type * 5 See also * 6 References * 7 Further reading * 8 External links ## Controversy[edit] In recent years, vaccination has become a controversial topic among veterinarians and pet owners. Specific adverse reactions and general consequences for long-term health and immunity are both being cited as reasons to reduce the frequency of pet vaccination. The 2010 pet vaccination guidelines[3] published by the WSAVA (World Small Animal Veterinary Association) reduce the number of vaccines which should be considered core for pets, as well as recommending less frequent vaccine administration. However, in an open letter to WSAVA,[4] an Australian pet owner and long-time consumer advocate has created a detailed critique of these guidelines, with numerous scholarly citations, arguing that the 3-year booster or re-vaccination recommendations are either arbitrary or influenced by vaccine manufacturers. She cites the scientific findings of both WSAVA's and other leading researchers, which indicate that, similar to humans, the duration of immunity (DOI) for pets vaccinated early in life with MLV (modified live viruses) is many years, if not the entirety of adulthood, despite the common practice of "boosting" vaccines every 1 to 3 years. In the executive summary section, the WSAVA guidelines[3] do argue against needless vaccination and in support of "the development and use of simple in-practice tests for determination of seroconversion (antibody) following vaccination." They also note that "Vaccines should not be given needlessly. Core vaccines should not be given any more frequently than every three years after the 12 month booster injection following the puppy/kitten series, because the duration of immunity (DOI) is many years and may be up to the lifetime of the pet." The open letter critique focuses on the less-nuanced summary of these recommendations in the Tables given for vaccination guidelines, which could imply that re-vaccination should occur every 3 years. ## Possible causes[edit] ### Vaccine-specific[edit] Adverse reactions usually occur because of a harmful immune-mediated reaction to either the vaccine immunogen itself or to the vaccine adjuvants, which are designed to boost the immune response to the vaccines. The immunogens may consist of killed or inactivated pathogens, bio-engineered pathogen proteins or polypeptides, or, increasingly rarely, modified live virus. There have been no specific associations between development of vaccine-associated sarcoma and vaccine brand or manufacturer, concurrent infections, history of trauma, or environment.[5] In 1993, a causal relationship between VAS and administration of aluminum adjuvanted rabies and FeLV vaccines was established through epidemiologic methods.[6] ### Animal-specific[edit] In addition to vaccine-specific factors, vets and owners should also consider pet-specific factors that have been shown to increase the risk of adverse reactions in both dogs[1] and cats.[2] Examples of such factors include: * age, * number of vaccinations per office visit, * size, * general health of the animal, * breed, * neutered status, and * past vaccination history. ## Types of reactions[edit] ### Ischemic Dermatopathy / Cutaneous Vasculitis[edit] A little known and often misdiagnosed reaction to the rabies vaccine in dogs, this problem may develop near or over the vaccine administration site and around the vaccine material that was injected, or as a more widespread reaction. Symptoms include ulcers, scabs, darkening of the skin, lumps at the vaccine site, and scarring with loss of hair. In addition to the vaccination site, lesions most often develop on the ear flaps (pinnae), on the elbows and hocks, in the center of the footpads and on the face. Scarring may be permanent. Dogs do not usually seem ill, but may develop fever. Symptoms may show up within weeks of vaccination, or may take months to develop noticeably. Dogs with active lesion development and / or widespread disease may be treated with pentoxyfylline, a drug that is useful in small vessel vasculitis, or tacrolimus, an ointment that will help suppress the inflammation in the affected areas. Owners and veterinarians of dogs who have developed this type of reaction should review the vaccination protocol critically and try to reduce future vaccinations to the extent medically and legally possible. At the very least, vaccines from the same manufacturer should be avoided. It is also recommended that the location in which future vaccinations are administered should be changed to the rear leg, as far down on the leg as possible and should be given in the muscle rather than under the skin. ### Urticaria / Anaphylaxis[edit] Fortunately, severe systemic reaction to vaccine allergy is very rare in dogs. When it does occur, however, anaphylaxis is a life-threatening emergency. More often, dogs will develop urticaria, or hives within minutes of receiving a vaccine. When this occurs, a veterinarian will treat the reaction with antihistamines and corticosteroid drugs and this is usually effective. Future vaccine protocols must be modified according to the vaccine component suspected to have triggered the reaction. ### Development of antibodies against kidney tissue[edit] FVRCP vaccines have also come under scrutiny of late due to possible risks to long term health. A study at Colorado State University noted an association between vaccination with parenteral (injectable) FVRCP vaccinations and development of antibodies against feline kidney tissue.[7] Antibody development is hypothesized to develop when the immune system reacts to protein contaminants from the cell line used to cultivate vaccinial viruses. The cell line in question, the Crandell-Rees Feline Kidney (CRFK) cell line, was derived from a cat kidney. It is currently unknown whether this antibody development can lead to renal disease, though a recent follow-up study demonstrated evidence of inflammation on re-biopsy samples from some of the study cats.[8] ### Sarcoma / Tumor[edit] A Vaccine-associated sarcoma (VAS) is a type of malignant tumor found in cats (and rarely, dogs and ferrets) that has been linked to certain vaccines. Concern about VAS has resulted in changes in recommended vaccine protocols to limit the type, frequency, and sites of vaccinations. Owners are advised to monitor injection sites for signs of tumors and contact their veterinarian immediately if one develops. ## Recommendations[edit] Concerns about these adverse reactions have led to revised guidelines in 2006,[9][10] 2010[3] and 2011[11] that address these concerns by altering the recommended frequency and methods/locations for both vaccination of dogs and feline vaccination. ### Location[edit] Vaccines should be given in specific areas in order to: ease identification of which vaccine caused an adverse reaction, and ease removal of any vaccine-associated sarcoma.[12] In North America, vets adopted the practice of injecting specific limbs as far from the body as possible,[13] with the rear right for rabies, the rear left for leukemia, and the right front shoulder (being careful to avoid the midline or interscapular space) for other vaccines (such as FVRCP). This set of locations was not widely adopted outside of North America, and the international Vaccination Guidelines Group (VGG) made new recommendations[3] that vaccines be administered: * in subcutaneous (and not intramuscular) sites * in the skin of the lateral thorax or abdomen (for easier excision of any FISS that occur) * avoid the interscapular or intercostal regions (as more extensive surgical resection would be needed for sarcomas) * in a different site on each occasion (either with general locations per species per year or diagrams of where administered on specific visit) ### Frequency and type[edit] In the 2010 recommendations of the international Vaccination Guidelines Group (VGG),[3] they emphasized the importance of administering non-adjuvanted vaccines whenever possible. The VGG also prefers serological testing over unnecessary re-vaccination or boosters of core vaccines after the initial 12-month booster that follows the puppy/kitten series of modified live virus [MLV] vaccines. This is because core vaccines show an excellent correlation between the presence of antibody and protective immunity and have a long DOI (Duration of Immunity). Antibody tests can be used to demonstrate the DOI after vaccination with core vaccines, though not for non-core vaccines. ## See also[edit] * Vaccination of dogs * Feline vaccination * Vaccine controversies * Vaccine Adverse Event Reporting System ## References[edit] 1. ^ a b Moore, George E.; Guptill, Lynn F.; Ward, Michael P.; Glickman, Nita W.; Faunt, Karen K.; Lewis, Hugh B.; Glickman, Lawrence T. (2005). "Adverse events diagnosed within three days of vaccine administration in dogs". Journal of the American Veterinary Medical Association. 227 (7): 1102–8. doi:10.2460/javma.2005.227.1102. PMID 16220670. 2. ^ a b Moore, George E.; Desantis-Kerr, Andrea C.; Guptill, Lynn F.; Glickman, Nita W.; Lewis, Hugh B.; Glickman, Lawrence T. (2007). "Adverse events after vaccine administration in cats: 2,560 cases (2002–2005)". Journal of the American Veterinary Medical Association. 231 (1): 94–100. doi:10.2460/javma.231.1.94. PMID 17605670. 3. ^ a b c d e "WSAVA Guidelines for the Vaccination of Dogs and Cats" (PDF). Vaccination Guidelines Group (VGG) of the World Small Animal Veterinary Association (WSAVA). 2010. Archived from the original (PDF) on 2012-05-26. Retrieved July 8, 2012. 4. ^ "Critique of the WSAVA VGG Vaccination Guidelines for Owners & Breeders of Dogs and Cats" (PDF). 2012-02-06. Retrieved August 26, 2012. 5. ^ Kass, Philip H.; Spangler, William L.; Hendrick, Mattie J.; McGill, Lawrence D.; Esplin, D. Glen; Lester, Sally; Slater, Margaret; Meyer, E. Kathryn; et al. (2003). "Multicenter case-control study of risk factors associated with development of vaccine-associated sarcomas in cats". Journal of the American Veterinary Medical Association. 223 (9): 1283–92. doi:10.2460/javma.2003.223.1283. PMID 14621215. 6. ^ Richards J, Elston T, Ford R, Gaskell R, Hartmann K, Hurley K, Lappin M, Levy J, Rodan I, Scherk M, Schultz R, Sparkes A (2006). "The 2006 American Association of Feline Practitioners Feline Vaccine Advisory Panel report". J Am Vet Med Assoc. 229 (9): 1405–41. doi:10.2460/javma.229.9.1405. PMID 17078805. 7. ^ "CVMBS — Fall 2004 Insight — Colorado State University". Archived from the original on 2012-06-30. Retrieved 2012-06-24. 8. ^ Lappin, M; Basaraba, R; Jensen, W (2006). "Interstitial nephritis in cats inoculated with Crandell Rees feline kidney cell lysates". Journal of Feline Medicine & Surgery. 8 (5): 353–6. doi:10.1016/j.jfms.2006.03.003. PMID 16713319. S2CID 20242445. 9. ^ "The 2006 American Association of Feline Practitioners Feline Vaccine Advisory Panel Report" (PDF). American Association of Feline Practitioners. Retrieved 2012-06-24.[permanent dead link] 10. ^ "Summary Table: Vaccination in General Practice" (PDF). The 2006 American Association of Feline Practitioners Feline Vaccine Advisory Panel Report. Retrieved 2012-06-24.[permanent dead link] 11. ^ "2011 AAHA Canine Vaccination Guidelines" (PDF). American Animal Hospital Association (AAHA) Canine Vaccination Task Force. 2011. Archived from the original (PDF) on 2012-05-15. Retrieved July 8, 2012. 12. ^ Eigner, Diane R. "Feline Vaccine Guidelines". The Winn Feline Foundation. Archived from the original on 2006-08-20. Retrieved 2006-08-27. 13. ^ "VAFSTF Vaccine Site Recommendations". Vaccine-Associated Feline Sarcoma Task Force of the American Association of Feline Practitioners (AAFP), American Animal Hospital Association (AAHA), American Veterinary Medical Association (AVMA), and Veterinary Cancer Society (VCS). Archived from the original on 2012-05-16. Retrieved 2012-06-23. ## Further reading[edit] * Moore, George E.; Hogenesch, Harm (2010). "Adverse Vaccinal Events in Dogs and Cats". Veterinary Clinics of North America: Small Animal Practice. 40 (3): 393–407. doi:10.1016/j.cvsm.2010.02.002. PMID 20471524. * Horzinek, Marian C.; Thiry, Etienne (2009). "Vaccines and vaccination: The principles and the polemics". Journal of Feline Medicine & Surgery. 11 (7): 530–7. doi:10.1016/j.jfms.2009.05.012. PMID 19481032. S2CID 30540653. * Dodet, Betty; Hesselink, Wim; Jungbäck, Carmen; Léchenet, Jacques; Pastoret, Paul-Pierre; Vannier, Philippe; Vicari, Marissa (2010). "Viral safety and extraneous agents testing for veterinary vaccines". Biologicals. 38 (3): 326–31. doi:10.1016/j.biologicals.2010.01.013. PMID 20503495. * Adams, G (2009). "Recommendation on the placement of vaccinations in cats". Journal of the American Veterinary Medical Association. 234 (8): 1005. doi:10.2460/javma.234.8.1005. PMID 19455740. * Jacob, C (2011). "Different perspectives on vaccination advice". Veterinary Record. 168 (15): 395–6. doi:10.1136/vr.d2311. PMID 21498448. S2CID 42476935. * Day, M. J. (2011). "Vaccination of dogs and cats: No longer so controversial?". Veterinary Record. 168 (18): 480–2. doi:10.1136/vr.d2810. PMID 21551198. S2CID 39276509. ## External links[edit] * Horzinek, MC (2010). "Vaccination protocols for companion animals: the veterinarian's perspective". Journal of Comparative Pathology. 142 Suppl 1: S129–32. doi:10.1016/j.jcpa.2009.11.001. PMID 19954796. * Vaccination Guidelines Group (VGG) of the World Small Animal Veterinary Association (WSAVA) (2010). "Vaccination guidelines for the owners and breeders of dogs and cats" (PDF). Archived from the original (PDF) on 2012-05-26. Retrieved 2012-06-24. * Vaccination Guidelines Group (VGG) of the World Small Animal Veterinary Association (WSAVA) (2010). "WSAVA guidelines for the vaccination of dogs and cats" (PDF). Archived from the original (PDF) on 2012-05-26. Retrieved 2012-06-24. * "Critique of the WSAVA VGG Vaccination Guidelines for Owners & Breeders of Dogs and Cats" (PDF). 2012-02-06. Retrieved August 26, 2012. * "Canine Vaccination Guidelines" (PDF). American Animal Hospital Association (AAHA) Canine Vaccination Task Force. 2011. Archived from the original (PDF) on 2012-05-15. Retrieved 2012-06-24. * "Feline Life Stage Guidelines" (PDF). American Association of Feline Practicitioners & American Animal Hospital Association. 2010. Archived from the original (PDF) on 2010-07-18. Retrieved 2012-08-26. * "Feline Vaccine Advisory Panel Report" (PDF). American Association of Feline Practitioners. 2006. Retrieved 2012-06-24.[permanent dead link] * American Association of Feline Practitioners (2006). "Summary Table: Vaccination in General Practice" (PDF). Feline Vaccine Advisory Panel Report. Retrieved 2012-06-24.[permanent dead link] * "Canine and Feline Vaccination Guidelines". UC Davis Veterinary Medical Teaching Hospital. November 2009. Retrieved 2012-08-26. * "vaccine Controversy". Top Dog Kennel. Retrieved 2012-06-24. * v * t * e Artificial induction of immunity / Immunization: Vaccines, Vaccination, Infection, Inoculation (J07) Development * Adjuvants * List of vaccine ingredients * Mathematical modelling * Timeline * Trials Classes * Conjugate vaccine * Inactivated vaccine * Live vector vaccine * Attenuated vaccine * Heterologous vaccine * Subunit/component / Peptide / Virus-like particle / Synthetic * DNA / RNA * Toxoid Administration * Global: * GAVI Alliance * NITAG * Policy * Schedule * Vaccine injury * US: * ACIP * Vaccine court * Vaccines for Children Program * VAERS * VSD Vaccines Bacterial * Anthrax * Brucellosis * Cholera# * Diphtheria# * Hib# * Leptospirosis * Lyme disease‡ * Meningococcus# * MeNZB * NmVac4-A/C/Y/W-135 * Pertussis# * Plague * Pneumococcal# * PCV * PPSV * Q fever * Tetanus# * Tuberculosis * BCG# * Typhoid# * Ty21a * ViCPS * Typhus * combination: * DPT/DTwP/DTaP * Td/Tdap * research: * Clostridioides difficile * Group B streptococcal disease * Shigellosis Viral * Adenovirus * COVID-19 * Oxford–AstraZeneca† * Moderna† * Pfizer-BioNTech† * Ebola * Flu# * H1N1 (Pandemrix) * H5N1 * LAIV * Hantavirus * Hepatitis A# * Hepatitis B# * Hepatitis E * HPV * Cervarix * Gardasil * Japanese encephalitis# * Measles# * Mumps# * Mumpsvax * Polio# * Sabin * Salk * Rabies# * Rotavirus# * Rubella# * Smallpox * Dryvax * Tick-borne encephalitis * Varicella zoster * Chicken pox# * Shingles * Yellow fever# * combination: * Hepatitis A and B * MMR * MMRV * research: * Chikungunya * COVID-19 * Cytomegalovirus * Dengue * Ebola * Epstein–Barr virus * Hepatitis C * Herpes simplex * HIV * Respiratory syncytial virus * Zika Protozoan * Malaria * RTS,S * research: * Trypanosomiasis Helminthiasis * research: * Hookworm * Schistosomiasis Other * Androvax (androstenedione albumin) * Cancer vaccines * ALVAC-CEA * BCG# * Hepatitis B# * HPV * Cervarix * Gardasil * Prostvac * NicVAX * Ovandrotone albumin (Fecundin) * TA-CD * TA-NIC * combination: * DTaP-IPV/Hib * DTaP-IPV-HepB * Hexavalent vaccine * Pentavalent vaccine Inventors/researchers * Edward Jenner * Louis Pasteur * Hilary Koprowski * Jonas Salk * John Franklin Enders * Maurice Hilleman * Stanley Plotkin * H. 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Secretary of Health and Human Services * Alternative vaccination schedule Related * Epidemiology * Eradication of infectious diseases * Every Child by Two * List of vaccine topics * #WHO-EM * ‡Withdrawn from market * Clinical trials: * †Phase III * §Never to phase III [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Adverse vaccine reactions in pets	None	25,699	wikipedia	https://en.wikipedia.org/wiki/Adverse_vaccine_reactions_in_pets	2021-01-18T19:03:19	{"wikidata": ["Q4686722"]}

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