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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: "Gynophobia" – news · newspapers · books · scholar · JSTOR (October 2014) (Learn how and when to remove this template message) Gynophobia or gynephobia is an abnormal fear of women, a type of specific social phobia.[1] In the past, the Latin term horror feminae was used.[2] Gynophobia should not be confused with misogyny, the hatred, contempt for and prejudice against women,[3][4] although some may use the terms interchangeably, in reference to the social, rather than pathological aspect of negative attitudes towards women.[5] The antonym of misogyny is philogyny, the love, respect for and admiration of women.[6] This term is analogous with androphobia, the abnormal or irrational fear of men. ## Contents * 1 Etymology * 2 History * 3 See also * 4 References ## Etymology The term gynophobia comes from the Greek γυνή - gunē, meaning "woman"[7] and φόβος - phobos, "fear".[8] Hyponyms of the term "gynophobia" include feminophobia,[9] ## History Gynophobia was previously considered a driving force toward homosexuality. In his 1896 Studies in the Psychology of Sex, Havelock Ellis wrote: > It is, perhaps, not difficult to account for the horror – much stronger than that normally felt toward a person of the same sex – with which the invert often regards the sexual organs of persons of the opposite sex. It cannot be said that the sexual organs of either sex under the influence of sexual excitement are esthetically pleasing; they only become emotionally desirable through the parallel excitement of the beholder. When the absence of parallel excitement is accompanied in the beholder by the sense of unfamiliarity as in childhood, or by a neurotic hypersensitiveness, the conditions are present for the production of intense horror feminae or horror masculis, as the case may be. It is possible that, as Otto Rank argues in his interesting study, "Die Nacktheit in Sage und Dichtung," [sic] this horror of the sexual organs of the opposite sex, to some extent felt even by normal people, is embodied in the Melusine type of legend.[10] In his book Sadism and Masochism: The Psychology of Hatred and Cruelty, Wilhelm Stekel discusses horror feminae of a male masochist. In The Dread of Woman (1932), Karen Horney traced the male dread of woman to the boy's fear that his genital is inadequate in relation to the mother.[11] Professor Eva Keuls argues that violent Amazons are the evidence of the obsessive fear of women in Classical Athens.[12] ## See also Look up gynophobia in Wiktionary, the free dictionary. * List of phobias ## References 1. ^ "WordNet". Princeton University. Retrieved 2014-07-09. 2. ^ Raymond Joseph Corsini (1999) "The Dictionary of Psychology", ISBN 1-58391-028-X, p. 452 3. ^ http://www.oxforddictionaries.com/definition/english/misogyny?q=misogyny 4. ^ http://www.merriam-webster.com/dictionary/misogyny 5. ^ Susan Gaylard, Hollow Men: Writing, Objects, and Public Image in Renaissance Italy, p. 86 6. ^ "WordNet". Princeton University. Retrieved 2014-07-09. 7. ^ γυνή, Henry George Liddell, Robert Scott, A Greek-English Lexicon, on Perseus 8. ^ φόβος, Henry George Liddell, Robert Scott, A Greek-English Lexicon, on Perseus 9. ^ The Shattered Mirror: Representations of Women in Mexican Literature, María Elena de Valdés, 2010, p 74 10. ^ Works of Havelock Ellis at Project Gutenberg 11. ^ Horney & Humanistic Psychoanalysis, http://plaza.ufl.edu/bjparis/ikhs/horney/fadiman/04_major.html 12. ^ Eva C. Keuls, "The Reign of the Phallus: Sexual Politics in Ancient Athens", ISBN 0-520-07929-9, pp. 3-4 * v * t * e Gender and sexual identities Gender identities Genders * Man * Woman * Male * Female * Androgynos * Androgyne * Boi * Cisgender * Cross-dresser * Gender bender * Gender neutrality * Non-binary (or genderqueer) * Postgenderism * Gender variance * Transgender * Trans man * Trans woman * Transsexual Third genders or third sexes * Akava'ine * Apwint * Bakla * Bugis genders * Bissu * Calabai * Calalai * Chibados * Enaree * Eunuch * Fa'afafine * Fakaleitī * Femminiello * Galli * Hijra * Kathoey * Khanith * Köçek * Koekchuch * Lhamana * Māhū * Mak nyah * Mukhannathun * Muxe * Nádleehi * Nullo * Rae-rae * Sipiniq * Sworn virgin * Takatāpui * Travesti * Tumtum * Two-spirit * Winkte Sexual orientation identities Sexual orientations * Asexual * Bisexual * Heterosexual * Homosexual Alternative labels * Banjee * Bi-curious * Ex-gay * Ex-ex-gay * Gay * Gray asexual * Heteroflexible * Lesbian * Non-heterosexual * Pansexual * Polysexual * Queer * Questioning * Same gender loving Social aspects * Sociosexuality * Antisexuality * Monogamy * Non-monogamy * Polyamorous * Asociality * Homosociality * Heterosociality Other * Analloeroticism * Androphilia and gynephilia * Attraction to transgender people * Kinsey scale * Monosexuality * Romantic orientation See also * Gender roles * Intersex * Sex and gender distinction * Sexuality and gender identity-based cultures * Social construction of gender [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Gynophobia	None	29,100	wikipedia	https://en.wikipedia.org/wiki/Gynophobia	2021-01-18T18:52:40	{"wikidata": ["Q1558456"]}
## Description The stiff-person syndrome (SPS) is most often an adult-onset sporadic acquired disorder characterized by progressive muscle stiffness with superimposed painful muscle spasms accompanied by electromyographic evidence of continuous motor activity at rest. SPS has been associated with autoimmune disorders, diabetes mellitus, thyrotoxicosis, and hypopituitarism with adrenal insufficiency (George et al., 1984). Approximately 60% of patients with SPS have antibodies to glutamic acid decarboxylase (GAD2, or GAD65; 138275), the rate-limiting enzyme in the synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), suggesting an immune-mediated pathogenesis (Folli et al., 1993). Approximately 10% of patients develop SPS as a paraneoplastic neurologic disorder associated with antibodies to amphiphysin (AMPH; 600418), an intracellular protein associated with neuronal synaptic vesicle endocytosis (Burns, 2005). See also congenital stiff-man syndrome, or hereditary hyperexplexia (149400), which is caused by mutations in subunits of the glycine receptor gene (GLRA1, 138491; GLRB, 138492). Meinck and Thompson (2002) provided a detailed review of stiff-person syndrome. They also discussed 2 possibly related conditions, progressive encephalomyelitis with rigidity (PERM), a more severe disorder with other neurologic features, and stiff-limb or stiff-leg syndrome, a focal disorder. Clinical Features Moersch and Woltman (1956) reported stiff-man syndrome in patients with progressive fluctuating muscular rigidity and spasms. Solimena et al. (1988) reported a patient with stiff-man syndrome characterized by fluctuating muscle rigidity with painful spasms. He also had type I diabetes mellitus (222100) and epilepsy. Elevated levels of IgG were found in serum and cerebrospinal fluid, which stained gray matter regions of brain sections in patterns identical to those produced by antibodies to glutamic acid decarboxylase. Both CSF and serum antibodies reacted with a band comigrating with GAD2 in sodium dodecyl sulfate-polyacrylamide gels, suggesting the possibility of an autoimmune pathogenesis. Meinck et al. (1994) reported 8 patients with stiff-man syndrome. All had adult onset of severe muscle stiffness and superimposed painful violent spasms or jerks including opisthotonos, stiffening of the arms and/or legs, and inversion of extended feet. Jerks and spasms were elicited by somatosensory stimuli to almost all parts of the body, even those uninvolved in the spasms. Five patients experienced by an aura-like feeling of an imminent attack, associated in some with fear and restlessness, beforehand. Seven patients had autonomic symptoms during attacks, including profuse sweating, tachycardia, hypertension, or pupillary dilation. All patients had been diagnosed earlier with hysterical anxiety neuroses. Two patients had additional features, such as nystagmus, vertigo, or paresthesias, consistent with 'progressive encephalomyelitis with rigidity and myoclonus.' EMG in all patients showed steady, low-frequency firing of normal motor units that abruptly increased in response to somatosensory or acoustic stimulation; these findings disappeared during natural or drug-induced sleep. Treatment with benzodiazepines or immunosuppression was effective. Four patients, including 1 with features of PERM, had anti-GAD antibodies; there was no difference in symptoms between those with and those without antibodies. Electrophysiologic studies by Meinck et al. (1995) identified a characteristic spasmodic reflex myoclonus in the trunk muscles induced from a wide peripheral receptive field. Dalakas et al. (2000) evaluated the clinical spectrum of 20 patients with anti-GAD antibodies and stiff-man syndrome. Average age at onset was 41.2 years. The characteristic clinical findings were muscle stiffness with superimposed episodic spasms and contractures of the abdominal and thoracic paraspinal muscles, as well as stiff gait with frequent falls. Thirteen patients had facial involvement. Autoimmune diseases or autoantibodies were noted in 80% of patients. Dalakas et al. (2000) noted that many patients were misdiagnosed due to multifaceted presentations. Burns et al. (2003) reported a father and daughter with SPS associated with anti-GAD65 antibodies. At age 53 years, the father developed rigidity of the extremities, which the authors termed the 'stiff-limb variant.' He had a personal history of pernicious anemia and thyroiditis and a family history of diabetes mellitus. His daughter developed recurrent, episodic extension of the head and neck at age 31 years. Her symptoms progressed over time, and she developed an opisthotonic response to tapping of the patellar tendon. Serum analysis showed anti-thyroperoxidase (TPO; 606765) antibodies in the absence of clinical thyroid disease. During this period, she gave birth to a healthy infant who did not exhibit clinical symptoms of SPS despite transient transplacental acquisition of maternal GAD65 antibodies. Low levels of anti-GAD65 antibodies were detected in the serum of 4 other family members without SPS. Rakocevic et al. (2004) found that many patients with stiff-person syndrome have comorbid neuropsychiatric disorders, including anxiety and depression. In a study of 16 patients, they found no correlation between GAD antibody titers and clinical severity as measured by a 'stiffness index.' The authors concluded that anti-GAD antibodies are a good marker for the disorder, but are not useful in monitoring progression. Nemni et al. (2004) reported the presence of high titer anti-GAD65 antibodies until age 24 months in 2 asymptomatic newborns of a woman with stiff-person syndrome. As the children were not breastfed, the antibodies were presumably acquired by passive transplacental transfer to the bloodstream of the infants. The authors suggested that the antibodies did not pass the blood-brain barrier in the infants, and thus were unable to attack the putative antigen, GABAergic neurons in the CNS. The children remained symptom-free at ages 6 and 8 years. Nemni et al. (2004) noted that up to 40% of patients with SPS do not have anti-GAD65 antibodies, and concluded that other cofactors are required for the development of the disorder. Using transcranial magnetic stimulation, Koerner et al. (2004) demonstrated that untreated patients with SPS or PER had significantly enhanced motor cortex excitability compared to treated patients or controls. Motor cortex excitability was more enhanced in patients with anti-GAD antibodies and correlated with antibody levels in CSF. The findings supported a disturbance of intrinsic cortical GABAergic neurotransmission in SPS and PER. In a neuropsychologic assessment of 10 patients with SPS, Ameli et al. (2005) concluded that fear, anxiety, and phobic symptoms were realistic and secondary to the symptoms of SPS rather than due to inherent primary phobic neuroses. Economides and Horton (2005) reported a 38-year-old woman with SPS and anti-GAD65 antibodies who had eye movement abnormalities in addition to muscle stiffness and ataxia. Oculomotor findings included gaze-holding nystagmus, limited abduction, ocular misalignment, deficient smooth pursuit, and impaired saccadic initiation. There was no evidence of myasthenia gravis (MG; 254200). Economides and Horton (2005) suggested that the oculomotor abnormalities were a primary manifestation of SPS, perhaps related to GABA depletion. Hutchinson et al. (2008) reported a 54-year-old man with clinical features of PERM associated with serum autoantibodies to the glycine receptor alpha-1 subunit (GLRA1; 138491). There was no evidence of malignancy. The clinical course was progressive, beginning with tingling sensation and spontaneous violent jerks of the limbs and trunk. He later developed ptosis, horizontal gaze palsies, facial weakness, spinal rigidity, and difficulty walking. Aggressive immunosuppressive therapy resulted in significant improvement. The authors noted that mutations in the GLRA1 gene result in hereditary hyperekplexia (149400), which is characterized by excessive startle response. Hutchinson et al. (2008) postulated that anti-GLRA1 antibodies may disrupt glycinergic inhibition in the brainstem and spinal cord. ### Stiff-Person Syndrome as a Paraneoplastic Syndrome Folli et al. (1993) reported 3 unrelated women with SPS and ductal breast cancer who had plasma and CSF autoantibodies to a 128-kD cytosolic protein concentrated at synapses in the central nervous system. None of the women had anti-GAD65 antibodies measured by different methods. Autoantibodies against the 128-kD protein were not detected in control patients with SPS without breast cancer or in patients with cancer who did not have SPS. Two of the patients presented clinically with SPS involving the proximal limb musculature and absence of truncal rigidity; symptoms resolved after cancer treatment in 1 patient, whereas the other patient showed deterioration with involvement of the trunk. The third patient had leg involvement and opisthotonos, with improvement after cancer treatment. Wessig et al. (2003) reported a 71-year-old woman with invasive ductal carcinoma and a paraneoplastic stiff-person syndrome characterized by stiffness in the right arm, stiff and unsteady gait, and increased sweating. Autoantibodies to amphiphysin (600418), a 128-kD protein, were detected in the patient's serum and CSF, and the patient temporarily responded to plasmapheresis. Postmortem studies detected anti-amphiphysin antibodies in the CNS parenchyma, suggesting a pathogenic role. Butler et al. (2000) identified high-titer autoantibodies directed against gephyrin (GPH; 603930) in a patient with mediastinal cancer and clinical features of stiff-man syndrome. Their findings provided evidence for a link between autoimmunity directed against components of inhibitory synapses and neurologic conditions characterized by chronic rigidity and spasms. Murinson and Guarnaccia (2008) evaluated 11 patients with SPS and amphiphysin autoantibodies. All were women, 10 of 11 had breast cancer, and none had diabetes. The patients had a later age at onset and tended to have a higher frequency of cervical and arm involvement with a broader distribution pattern of stiffness compared to 112 SPS patients with anti-GAD antibodies. Four patients showed a favorable response to steroid treatment, and 3 of 5 showed marked improvement after tumor excision and chemotherapy. The findings suggested that amphiphysin antibody-associated SPS is distinct from GAD antibody-associated SPS. Clinical Management Amato et al. (1994) used intravenous immunoglobulin to treat 3 patients with sporadic stiff-man syndrome and detectable serum antibodies to GAD. All 3 patients showed subjective and objective improvement. Dalakas et al. (2001) did a control study of 16 patients who had stiff-person syndrome and anti-GAD65 antibodies. The patients received intravenous immunoglobulin, which was well tolerated and effective. In a woman with stiff-person syndrome, Ruegg et al. (2004) reported successful treatment using levetiracetam, an antiepileptic drug that facilitates GABAergic transmission in the central nervous system. The treatment primarily resolved increasing and painful paroxysmal spasms and was effective during 2 years of follow-up. Hattan et al. (2008) reported successful treatment of SPS with low doses of intravenous propofol in a 70-year-old female patient. Pathogenesis Using MR spectroscopy, Levy et al. (2005) found that 8 patients with SPS had decreased levels of GABA in the sensorimotor cortex compared to 16 controls. Two patients with severe SPS who were wheelchair-bound or bedridden had more significant reductions in GABA (32 and 52% less than controls) than the other patients. None of the patients had structural abnormalities on brain imaging. The findings were consistent with decreased GABAergic function resulting in impaired inhibitory neurotransmission. Sommer et al. (2005) demonstrated that intraperitoneal injection of purified plasma anti-amphiphysin IgG antibodies from a patient with paraneoplastic SPS (Wessig et al., 2003) into female rats resulted in dose-dependent stiffness with spasms resembling human SPS. Analysis of the brain and spinal cord demonstrated that human IgG antibodies had crossed that blood-brain barrier in symptomatic animals. The findings showed that passive transfer of IgG antibodies were sufficient to cause the disorder in animals, suggesting that anti-amphiphysin antibodies are pathogenic in paraneoplastic SPS. Animal Model Gilbert et al. (2006) proposed that the 'hypertonic' mutant mouse (hyrt) is a model for stiff-man syndrome. They showed that the gene responsible for the hyrt phenotype is that encoding trafficking protein, kinesin-binding 1 (TRAK1; 608112). Hyrt mutant mice have much lower levels of GABA(A) receptors in the CNS, particularly the lower motor neurons, than do wildtype mice, indicating that the hypertonicity of the mutants is likely to be caused by deficits in GABA-mediated motor neuron inhibition. INHERITANCE \- Isolated cases CARDIOVASCULAR Heart \- Tachycardia Vascular \- Hypertension SKIN, NAILS, & HAIR Skin \- Diaphoresis NEUROLOGIC Central Nervous System \- Muscle stiffness and rigidity, chronic, fluctuating \- Axial muscle stiffness, symmetric \- Proximal limb muscle stiffness \- Limb muscle stiffness is often asymmetric \- Rigidity \- Stiff gait \- Frequent falls \- Lumbar paraspinal rigidity causes exaggerated lumbar lordosis \- Myoclonic spasms, superimposed episodic, severe, painful (characterized by activation of antagonistic muscle pairs, may involve facial muscles) \- Heightened sensitivity to external stimuli \- Increased startle response \- Opisthotonus \- Hyperreflexia \- EMG shows involuntary continuous motor activity at rest \- Autonomic features may occur (diaphoresis, tachycardia, hyperthermia, hypertension) Behavioral Psychiatric Manifestations \- Anxiety \- Depression \- Agoraphobia \- Specific phobias METABOLIC FEATURES \- Hyperthermia IMMUNOLOGY \- Associated with autoimmune disorders (e.g., diabetes mellitus, thyroiditis, pernicious anemia, vitiligo) \- Associated with autoantibodies to GAD65 (anti-glutamic acid decarboxylase GAD2, 138275 ) in serum and/or cerebrospinal fluid \- Approximately 60% of patients have anti-GAD65 antibodies \- Associated with serum autoantibodies to GLRA1 (glycine receptor alpha-1 subunit 138491 , reported in 1 patient) NEOPLASIA \- Approximately 10% of cases are paraneoplastic \- Paraneoplastic SPS is associated with breast cancer and other malignancies \- Paraneoplastic SPS is associated with autoantibodies to amphiphysin (AMPH, 600418 ) MISCELLANEOUS \- Adult onset \- Acquired sporadic disorder \- Episodes may be precipitated by fear, unexpected noises, emotional responses, movement \- Good response to immunotherapy (intravenous IgG or plasmapheresis) \- Good response to GABA-enhancing medications \- See also congenital stiff person syndrome ( 149400 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	STIFF-PERSON SYNDROME	c0085292	29,101	omim	https://www.omim.org/entry/184850	2019-09-22T16:34:10	{"doid": ["13366"], "mesh": ["D016750"], "omim": ["184850"], "icd-9": ["333.91"], "icd-10": ["G25.82"], "orphanet": ["443192", "3198", "438266", "443804"], "synonyms": ["STIFF-MAN SYNDROME", "Alternative titles", "STIFF-TRUNK SYNDROME", "Classic SPS"]}
The familial type of medullary thyroid carcinoma (155240) is a well-defined clinical entity. However, much less is known about the familial occurrence of differentiated thyroid carcinoma. Two patterns of presentation had been described for familial differentiated thyroid cancer: a pattern associated with an inherited tumor syndrome such as Gardner syndrome (APC; 175100) and Cowden disease (158350), and a second pattern of familial aggregation without other associated neoplasms. A further classification of thyroid tumors is based on size: papillary microcarcinoma of the thyroid is defined as a papillary carcinoma measuring 1.0 cm or less in diameter. This group of patients has been thought to be a specific low-risk category with a favorable prognosis (Hay et al., 1992). Lupoli et al. (1999) identified a family history of thyroid carcinoma in 7 of 119 patients with papillary thyroid microcarcinoma. The tumor was multifocal in 5 patients, bilateral in 3, and showed vascular invasion in 3 of the 7 patients. Lymph node metastases were found in 4 patients. Three patients had a recurrence and 1 patient with pulmonary metastases died within 11 months. Thus, familial occurrence was observed in 5.9% of cases, together with an unfavorable behavior of the familial form of the disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	PAPILLARY THYROID MICROCARCINOMA	c1709457	29,102	omim	https://www.omim.org/entry/603744	2019-09-22T16:12:45	{"mesh": ["C563277"], "omim": ["603744"], "orphanet": ["319487"], "synonyms": ["FNMTC", "Familial pure nonmedullary thyroid carcinoma"]}
Ink spot lentigo Other namesSunburn tentigo SpecialtyDermatology Ink spot lentigo is a cutaneous condition characterized by skin lesions commonly occurring on the shoulders.[1] These lesions often cause alarm but are benign. They are an indication of excessive sun exposure so although ink spot lentigo is not premalignant, people with several of them maybe at increased risk of skin cancer due to UV damage. For a safe diagnosis, they must be flat. Although the shape is irregular, the structure as seen on dermoscopy is very homogenous.[2] ## See also[edit] * Lentigo * Skin lesion ## References[edit] 1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. p. 686. ISBN 978-0-7216-2921-6. 2. ^ "ink spot lentigo". 18 June 2015. This cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Ink spot lentigo	None	29,103	wikipedia	https://en.wikipedia.org/wiki/Ink_spot_lentigo	2021-01-18T18:42:51	{"wikidata": ["Q6034519"]}
Spinal atrophy-ophthalmoplegia-pyramidal syndrome is a rare, bulbospinal muscular atrophy characterized by generalized neonatal hypotonia, progressive pontobulbar and spinal palsy, pyramidal signs, and deafness. External ophthalmoplegia and bilateral mydriasis are typical signs. There have been no further descriptions in the literature since 1994. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Spinal atrophy-ophthalmoplegia-pyramidal syndrome	c2930956	29,104	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1217	2021-01-23T18:34:53	{"gard": ["4942"], "mesh": ["C535625"], "umls": ["C2930956"], "icd-10": ["G12.2"], "synonyms": ["Hamano-Tsukamoto syndrome"]}
A number sign (#) is used with this entry because of evidence that autosomal recessive spastic paraplegia-43 (SPG43) is caused by homozygous mutation in the C19ORF12 gene (614297) on chromosome 19q12. One such family has been reported. Mutation in the C19ORF12 gene can also cause neurodegeneration with brain iron accumulation-4 (NBIA4; 614298), which shows overlapping but additional neurologic features. Description Spastic paraplegia-43 (SPG43) is an autosomal recessive neurodegenerative disorder characterized by childhood onset of progressive spasticity affecting the lower and upper limbs (summary by Meilleur et al., 2010). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see 270800. Clinical Features Meilleur et al. (2010) reported 2 sisters from Mali with childhood-onset spastic paraplegia. The girls had onset at ages 7 and 12 years, respectively, of difficulty walking due to progressive spasticity of the lower limbs. Physical examination of the older girl at age 19 years showed mild weakness of the proximal lower limb muscles, contractures of the knees and ankles, and pes cavus. Plantar responses were extensor, and there was marked bilateral spasticity in the legs. The upper limbs were also affected, with distal muscle atrophy, particularly of the intrinsic hand muscles, flexion contractures of the fingers, and decreased fine motor skills in the hands. There was also decreased vibration sense in the lower limbs. The younger sister was similarly, but more mildly, affected. Brain imaging was not feasible due to the family's remote location. Cognition in both sisters was normal. On reexamination of the older sister 5 years after the original report by Meilleur et al. (2010), Landoure et al. (2013) noted that she had severe atrophy and decreased sensation in the arms and legs with decreased reflexes, but no cognitive decline, facial or bulbar weakness, or vision loss. Brain MRI showed no abnormalities and no iron deposition. Inheritance The transmission pattern of SPG43 in the family reported by Meilleur et al. (2010) was consistent with autosomal recessive inheritance. Mapping By homozygosity mapping of 2 sisters from Mali with SPG, Meilleur et al. (2010) found a common 17.7-Mb region on chromosome 19p13.11-q12 between SNPs rs36692 and rs12460915. Sequencing of several candidate genes in the region did not identify any mutations. Molecular Genetics In 2 sisters, born of consanguineous Malian parents, originally reported by Meilleur et al. (2010) as having autosomal recessive SPG43, Landoure et al. (2013) identified a homozygous missense mutation in the C19ORF12 gene (A63P; 614297.0006). The mutation was found by exome sequencing of 1 of the sisters. The homozygous mutation was not found in 298 Malian controls or in 951 samples in the ClinSeq cohort. The A63P variant was present in 3 of 3,836 African American alleles in the NHLBI Exome Sequencing Project database, but not in 8,222 European American alleles from this database. Sequencing the coding region of C19ORF12 in 16 Australians, 46 French, 195 Americans, and 170 Japanese presenting with hereditary spastic paraplegia did not identify any other variants, suggesting that C19ORF12 mutation is likely a rare cause of this phenotype. Landoure et al. (2013) identified the same homozygous A63P mutation in 2 sibs from a consanguineous Brazilian family with NBIA4, and haplotype analysis indicated a founder effect between the Malian and Brazilian families. Landoure et al. (2013) suggested that the phenotypic differences between the 2 families may be due to other genetic or environmental factors or stochastic effects, and concluded that C19ORF12 mutations cause a neurologic disease spectrum that may or may not include brain iron deposition. INHERITANCE \- Autosomal recessive SKELETAL Limbs \- Contractures of the knees \- Contractures of the ankles Hands \- Contractures of the fingers \- Atrophy of the intrinsic hand muscles Feet \- Pes cavus MUSCLE, SOFT TISSUES \- Distal muscle atrophy, upper and lower limbs \- Distal muscle weakness, upper and lower limbs NEUROLOGIC Central Nervous System \- Spasticity \- Gait difficulties \- Difficulties in fine movement of the hands \- Dysarthria (mild) \- Hyperreflexia \- Extensor plantar responses Peripheral Nervous System \- Distal sensory impairment \- Hyporeflexia MISCELLANEOUS \- Onset in first decade \- Slowly progressive \- Variable severity \- One family of Mali origin has been reported (last curated January 2013) MOLECULAR BASIS \- Caused by mutation in the chromosome 19 open reading frame 12 gene (C19ORF12, 614297.0006 ) ▲ 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	SPASTIC PARAPLEGIA 43, AUTOSOMAL RECESSIVE	c2680446	29,105	omim	https://www.omim.org/entry/615043	2019-09-22T15:53:18	{"doid": ["0110795"], "omim": ["615043"], "orphanet": ["320370"], "synonyms": ["SPG43"]}
"Buerger disease" redirects here. It is not to be confused with Berger's disease. Thromboangiitis obliterans Other namesBuerger disease, Buerger's disease, Winiwarter-Buerger disease, presenile gangrene[1] Complete occlusion of the right and stenosis of the left femoral artery as seen in a case of thromboangiitis obliterans SpecialtyCardiology, rheumatology Thromboangiitis obliterans, also known as Buerger disease (English /bɜːrɡər/; German pronunciation: [/byːɐ̯gəɐ̯/]), is a recurring progressive inflammation and thrombosis (clotting) of small and medium arteries and veins of the hands and feet. It is strongly associated with use of tobacco products,[2] primarily from smoking, but is also associated with smokeless tobacco.[3][4] ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 3 Diagnosis * 4 Prevention * 5 Treatment * 6 Prognosis * 7 Epidemiology * 8 History * 9 Notable sufferers * 10 References * 11 Further reading * 12 External links ## Signs and symptoms[edit] There is a recurrent acute and chronic inflammation and thrombosis of arteries and veins of the hands and feet. The main symptom is pain in the affected areas, at rest and while walking (claudication).[1] The impaired circulation increases sensitivity to cold. Peripheral pulses are diminished or absent. There are color changes in the extremities. The colour may range from cyanotic blue to reddish blue. Skin becomes thin and shiny. Hair growth is reduced. Ulcerations and gangrene in the extremities are common complications, often resulting in the need for amputation of the involved extremity.[5] ## Pathophysiology[edit] There are characteristic pathologic findings of acute inflammation and thrombosis (clotting) of arteries and veins of the hands and feet (the lower limbs being more common). The mechanisms underlying Buerger's disease are still largely unknown, but smoking and tobacco consumption are major factors associated with it. It has been suggested that the tobacco may trigger an immune response in susceptible persons or it may unmask a clotting defect, either of which could incite an inflammatory reaction of the vessel wall.[6] This eventually leads to vasculitis and ischemic changes in distal parts of limbs. A possible role for Rickettsia in this disease has been proposed.[7] ## Diagnosis[edit] A concrete diagnosis of thromboangiitis obliterans is often difficult as it relies heavily on exclusion of other conditions. The commonly followed diagnostic criteria are outlined below although the criteria tend to differ slightly from author to author. Olin (2000) proposes the following criteria:[8] 1. Typically between 20–40 years old and male, although recently females have been diagnosed.[9] 2. Current (or recent) history of tobacco use. 3. Presence of distal extremity ischemia (indicated by claudication, pain at rest, ischemic ulcers or gangrene) documented by noninvasive vascular testing such as ultrasound. 4. Exclusion of other autoimmune diseases, hypercoagulable states, and diabetes mellitus by laboratory tests. 5. Exclusion of a proximal source of emboli by echocardiography and arteriography. 6. Consistent arteriographic findings in the clinically involved and noninvolved limbs. Buerger's disease can be mimicked by a wide variety of other diseases that cause diminished blood flow to the extremities. These other disorders must be ruled out with an aggressive evaluation, because their treatments differ substantially from that of Buerger's disease, for which there is no treatment known to be effective. Some diseases with which Buerger's disease may be confused include atherosclerosis (build-up of cholesterol plaques in the arteries), endocarditis (an infection of the lining of the heart), other types of vasculitis, severe Raynaud's phenomenon associated with connective tissue disorders (e.g., lupus or scleroderma), clotting disorders or the production of clots in the blood. Angiograms of the upper and lower extremities can be helpful in making the diagnosis of Buerger's disease. In the proper clinical setting, certain angiographic findings are diagnostic of Buerger's. These findings include a “corkscrew” appearance of arteries that result from vascular damage, particularly the arteries in the region of the wrists and ankles. Collateral circulation gives "tree root" or "spider leg" appearance.[1] Angiograms may also show occlusions (blockages) or stenosis (narrowings) in multiple areas of both the arms and legs. Distal plethysmography also yields useful information about circulatory status in digits. To rule out other forms of vasculitis (by excluding involvement of vascular regions atypical for Buerger's), it is sometimes necessary to perform angiograms of other body regions (e.g., a mesenteric angiogram). Skin biopsies of affected extremities are rarely performed because of the frequent concern that a biopsy site near an area poorly perfused with blood will not heal well. ## Prevention[edit] Further information: Thrombosis prophylaxis The cause of the disease is thought to be autoimmune in nature and heavily linked to tobacco use in patients with Buerger's as primary disease.[clarification needed] ## Treatment[edit] Smoking cessation has been shown to slow the progression of the disease and decrease the severity of amputation in most patients, but does not halt the progression. Treatment by 100% hyperbaric oxygen. In acute cases, drugs and procedures which cause vasodilation are effective in reducing pain experienced by patient. For example, prostaglandins like Limaprost[10] are vasodilators and give relief of pain, but do not help in changing the course of disease. Epidural anesthesia and hyperbaric oxygen therapy also have vasodilator effect.[1] A 2020 Cochrane review found moderate certainty evidence that intravenous iloprost (prostacyclin analogue) is more effective than aspirin for relieving rest pain and healing ischemic ulcers and that there is no difference between iloprost or clinprost (prostacyclin) and alprostadil (prostaglandin analogue) for relieving pain and healing ulcers.[11] In chronic cases, lumbar sympathectomy may be occasionally helpful.[12] It reduces vasoconstriction and increases blood flow to limb. It aids in healing and giving relief from pain of ischemic ulcers.[1] Bypass can sometimes be helpful in treating limbs with poor perfusion secondary to this disease. Use of vascular growth factor and stem cell injections have been showing promise in clinical studies. There may be a benefit of using bone marrow-derived stem cells in healing ulcers and improving pain-free walking distance, but larger, high-quality trials are needed.[13] Debridement is done in necrotic ulcers. In gangrenous digits, amputation is frequently required. Above-knee and below-knee amputation is rarely required.[1] Streptokinase has been proposed as adjuvant therapy in some cases.[14] Despite the clear presence of inflammation in this disorder, anti-inflammatory agents such as corticosteroids have not been shown to be beneficial in healing, but do have significant anti-inflammatory and pain relief qualities in low dosage intermittent form. Similarly, strategies of anticoagulation have not proven effective. physical therapy: interferential current therapy to decrease inflammation. ## Prognosis[edit] Buerger's is not immediately fatal. Amputation is common and major amputations (of limbs rather than fingers/toes) are almost twice as common in patients who continue to smoke. Prognosis markedly improves if a person quits smoking. Female patients tend to show much higher longevity rates than men. The only known way to slow the progression of the disease is to abstain from all tobacco products. ## Epidemiology[edit] Buerger's is more common among men than women. Although present worldwide, it is more prevalent in the Middle East and Far East.[15] Incidence of thromboangiitis obliterans is 8 to 12 per 100,000 adults in the United States (0.75% of all patients with peripheral vascular disease).[15] ## History[edit] Buerger's disease was first reported by Felix von Winiwarter in 1879 in Austria.[16] It was not until 1908, however, that the disease was given its first accurate pathological description, by Leo Buerger at Mount Sinai Hospital in New York City.[17] Buerger called it "presenile spontaneous gangrene" after studying amputations in 11 patients. ## Notable sufferers[edit] As reported by Alan Michie in God Save The Queen, published in 1952 (see pages 194 and following), King George VI was diagnosed with the disease on 12 November 1948. Both legs were affected, the right more seriously than the left. The king's doctors prescribed complete rest and electric treatment to stimulate circulation, but as they were either unaware of the connection between the disease and smoking (the king was a heavy smoker) or unable to persuade the king to stop smoking, the disease failed to respond to their treatment. On 12 March 1949, the king underwent a lumbar sympathectomy, performed at Buckingham Palace by James R. Learmonth. The operation, as such, was successful, but the king was warned that it was a palliative, not a cure, and that there could be no assurance that the disease would not grow worse. From all accounts, the king continued to smoke. The author and journalist John McBeth describes his experiences of the disease, and treatment for it, in the chapter "Year of the Leg" in his book Reporter. Forty Years Covering Asia.[18] Philippine president Rodrigo Duterte disclosed in 2015 that he has Buerger's disease.[19] ## References[edit] 1. ^ a b c d e f Ferri FF (2003). Ferri's Clinical Advisor 2004: Instant Diagnosis and Treatment. 6th edition. p. 840. ISBN 978-0323026680. 2. ^ Joyce JW (May 1990). "Buerger's disease (thromboangiitis obliterans)". Rheumatic Diseases Clinics of North America. 16 (2): 463–70. PMID 2189162. 3. ^ Mayo Clinic Staff. "Overview of Buerger's disease". Mayo Clinic. Retrieved 13 February 2016. 4. ^ "Thromboangiitis obliterans". Medline Plus. U.S. National Library of Medicine. Retrieved 13 February 2016. 5. ^ Porth C (2007). Essentials of Pathophysiology: Concepts of Altered Health States (2nd ed.). Lippincott Williams&Wilkins. p. 264. ISBN 9780781770873. 6. ^ Tanaka K (October 1998). "Pathology and pathogenesis of Buerger's disease". International Journal of Cardiology. 66 Suppl 1: S237-42. doi:10.1016/s0167-5273(98)00174-0. PMID 9951825. 7. ^ Fazeli B, Ravari H, Farzadnia M (December 2012). "Does a species of Rickettsia play a role in the pathophysiology of Buerger's disease?". Vascular. 20 (6): 334–6. doi:10.1258/vasc.2011.cr0271. PMID 21803838. 8. ^ Olin JW (September 2000). "Thromboangiitis obliterans (Buerger's disease)". The New England Journal of Medicine. 343 (12): 864–9. doi:10.1056/NEJM200009213431207. PMID 10995867. 9. ^ Atlas of Clinical Diagnosis (2nd ed.). Elsevier Health Sciences. 2003. p. 238. ISBN 9780702026683. 10. ^ Matsudaira K, Seichi A, Kunogi J, Yamazaki T, Kobayashi A, Anamizu Y, et al. (January 2009). "The efficacy of prostaglandin E1 derivative in patients with lumbar spinal stenosis". Spine. 34 (2): 115–20. doi:10.1097/BRS.0b013e31818f924d. PMID 19112336. 11. ^ Cacione, Daniel G.; Macedo, Cristiane R.; do Carmo Novaes, Frederico; Baptista-Silva, Jose Cc (4 May 2020). "Pharmacological treatment for Buerger's disease". The Cochrane Database of Systematic Reviews. 5: CD011033. doi:10.1002/14651858.CD011033.pub4. ISSN 1469-493X. PMC 7197514. PMID 32364620. 12. ^ Clinical Surgery (2nd ed.). John Wiley & Sons. 2012. ISBN 978111834395-1. 13. ^ Cacione DG, do Carmo Novaes F, Moreno DH (October 2018). Cochrane Vascular Group (ed.). "Stem cell therapy for treatment of thromboangiitis obliterans (Buerger's disease)". The Cochrane Database of Systematic Reviews. 10: CD012794. doi:10.1002/14651858.CD012794.pub2. PMC 6516882. PMID 30378681. 14. ^ Hussein EA, el Dorri A (1993). "Intra-arterial streptokinase as adjuvant therapy for complicated Buerger's disease: early trials". International Surgery. 78 (1): 54–8. PMID 8473086. 15. ^ a b Piazza G, Creager MA (April 2010). "Thromboangiitis obliterans". Circulation. 121 (16): 1858–61. doi:10.1161/CIRCULATIONAHA.110.942383. PMC 2880529. PMID 20421527. 16. ^ von Winiwarter F (1879). "Ueber eine eigenthumliche Form von Endarteriitis und Endophlebitis mit Gangran des Fusses". Arch Klin Chir. 23: 202–26. 17. ^ Buerger L (July 1953). "Thromboangiitis Obliterans". The Indian Medical Gazette. 88 (7): 395–396. doi:10.1097/00000441-190810000-00011. PMC 5202473. PMID 29015658. 18. ^ McBeth 2011, pp. 254-264. 19. ^ Frialde M (December 10, 2015). "Duterte: I may not last 6 years in office". The Philippine Star. Retrieved December 17, 2015. ## Further reading[edit] * Aktoz T, Kaplan M, Yalcin O, Atakan IH, Inci O (December 2008). "Penile and scrotal involvement in Buerger's disease". Andrologia. 40 (6): 401–3. doi:10.1111/j.1439-0272.2008.00859.x. PMID 19032693. * McBeth J (2011). Reporter. Forty Years Covering Asia. Singapore: Talisman Publishing. ISBN 9789810873646. ## External links[edit] Classification D * ICD-10: I73.1 * ICD-9-CM: 443.1 * OMIM: 211480 * MeSH: D013919 * DiseasesDB: 1762 External resources * MedlinePlus: 000172 * eMedicine: med/253 * Patient UK: Thromboangiitis obliterans * 00394 at CHORUS * Arkkila, PE, (2006), Thromboangiitis obliterans (Buerger's disease), Orphanet Journal of Rare Diseases * v * t * e Cardiovascular disease (vessels) Arteries, arterioles and capillaries Inflammation * Arteritis * Aortitis * Buerger's disease Peripheral artery disease Arteriosclerosis * Atherosclerosis * Foam cell * Fatty streak * Atheroma * Intermittent claudication * Critical limb ischemia * Monckeberg's arteriosclerosis * Arteriolosclerosis * Hyaline * Hyperplastic * Cholesterol * LDL * Oxycholesterol * Trans fat Stenosis * Carotid artery stenosis * Renal artery stenosis Other * Aortoiliac occlusive disease * Degos disease * Erythromelalgia * Fibromuscular dysplasia * Raynaud's phenomenon Aneurysm / dissection / pseudoaneurysm * torso: Aortic aneurysm * Abdominal aortic aneurysm * Thoracic aortic aneurysm * Aneurysm of sinus of Valsalva * Aortic dissection * Aortic rupture * Coronary artery aneurysm * head / neck * Intracranial aneurysm * Intracranial berry aneurysm * Carotid artery dissection * Vertebral artery dissection * Familial aortic dissection Vascular malformation * Arteriovenous fistula * Arteriovenous malformation * Telangiectasia * Hereditary hemorrhagic telangiectasia Vascular nevus * Cherry hemangioma * Halo nevus * Spider angioma Veins Inflammation * Phlebitis Venous thrombosis / Thrombophlebitis * primarily lower limb * Deep vein thrombosis * abdomen * Hepatic veno-occlusive disease * Budd–Chiari syndrome * May–Thurner syndrome * Portal vein thrombosis * Renal vein thrombosis * upper limb / torso * Mondor's disease * Paget–Schroetter disease * head * Cerebral venous sinus thrombosis * Post-thrombotic syndrome Varicose veins * Gastric varices * Portacaval anastomosis * Caput medusae * Esophageal varices * Hemorrhoid * Varicocele Other * Chronic venous insufficiency * Chronic cerebrospinal venous insufficiency * Superior vena cava syndrome * Inferior vena cava syndrome * Venous ulcer Arteries or veins * Angiopathy * Macroangiopathy * Microangiopathy * Embolism * Pulmonary embolism * Cholesterol embolism * Paradoxical embolism * Thrombosis * Vasculitis Blood pressure Hypertension * Hypertensive heart disease * Hypertensive emergency * Hypertensive nephropathy * Essential hypertension * Secondary hypertension * Renovascular hypertension * Benign hypertension * Pulmonary hypertension * Systolic hypertension * White coat hypertension Hypotension * Orthostatic hypotension [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Thromboangiitis obliterans	c0040021	29,106	wikipedia	https://en.wikipedia.org/wiki/Thromboangiitis_obliterans	2021-01-18T19:08:58	{"gard": ["5969"], "mesh": ["D013919"], "umls": ["C0040021"], "orphanet": ["36258"], "wikidata": ["Q746001"]}
A number sign (#) is used with this entry because of evidence that Townes-Brocks syndrome-2 (TBS2) is caused by heterozygous mutation in the DACT1 gene (607861) on chromosome 14q23. One such family has been reported. For a discussion of genetic heterogeneity of Townes-Brocks syndrome, see TBS1 (107480). Clinical Features Webb et al. (2017) studied a family in which 6 members exhibited features overlapping those of Townes-Brocks syndrome. The proband was a 20-month-old girl who was born with imperforate anus, rectovaginal fistula, crossed fused renal ectopia, and vesicoureteral reflux. In addition, her right ear was smaller than the left, and both ears showed overfolding of the superior helix and cupping, which was more pronounced on the right. Her 7-year-old brother also exhibited imperforate anus, as well as hypospadias, crossed fused renal ectopia, vesicoureteral reflux, and overfolding of both ears that was more pronounced on the right and also involved cupping on the right. Their mother had bilateral ear cupping, and spina bifida occulta had been diagnosed in her teen years. The mother's half-sister had severe microtia of the left ear, as did the proband's maternal grandmother, who also had bifid uterus. Molecular Genetics By whole-exome sequencing in a 3-generation family segregating features of Townes-Brocks syndrome, negative for mutation in the SALL1 gene (602218), Webb et al. (2017) identified heterozygosity for a nonsense mutation in the DACT1 gene (W419X; 607861.0001) that segregated fully with disease and was not found in public variant databases. The authors noted that identification of additional affected individuals with DACT1 mutations was necessary to understand the full spectrum of disease. INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Unilateral microtia \- Overfolded helices \- Cupped ears ABDOMEN Gastrointestinal \- Imperforate anus \- Rectovaginal fistula GENITOURINARY External Genitalia (Male) \- Hypospadias Internal Genitalia (Female) \- Bifid uterus Kidneys \- Crossed fused renal ectopia Bladder \- Reflux SKELETAL Spine \- Scoliosis \- Spina bifida occulta MISCELLANEOUS \- Based on report of 1 family \- Thumb abnormalities were not observed in this family MOLECULAR BASIS \- Caused by mutation in the antagonist of beta-catenin 1 Dapper (DACT, 607861.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	TOWNES-BROCKS SYNDROME 2	c0265246	29,107	omim	https://www.omim.org/entry/617466	2019-09-22T15:45:49	{"mesh": ["C536974"], "omim": ["617466"], "orphanet": ["857"]}
This article is about the medical condition. For other uses, see Narcolepsy (disambiguation). Human sleep disorder that involves an excessive urge to sleep and other neurological features Narcolepsy The concentration of orexin-A neuropeptides in the cerebrospinal fluid of narcoleptic individuals is usually very low Pronunciation * /ˈnɑːrkəˌlɛpsi/ SpecialtySleep medicine, neurology SymptomsExcessive daytime sleepiness, involuntary sleep episodes, sudden loss of muscle strength, hallucinations[1] ComplicationsMotor vehicle collisions, falls[1] Usual onsetChildhood[1] DurationLong term[1] CausesUnknown[1] Risk factorsFamily history, brain injury[1] Diagnostic methodBased on the symptoms and sleep studies[1] Differential diagnosisSleep apnea, major depressive disorder, anemia, heart failure, drinking alcohol, not getting enough sleep[1] TreatmentRegular short naps, sleep hygiene[1] MedicationModafinil, sodium oxybate, stimulants, antidepressants[1] Frequency0.2 to 600 per 100,000[2] Narcolepsy is a long-term neurological disorder that involves a decreased ability to regulate sleep-wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. About 70% of those affected also experience episodes of sudden loss of muscle strength, known as cataplexy. These experiences can be brought on by strong emotions. Less commonly, there may be vivid hallucinations or an inability to move (sleep paralysis) while falling asleep or waking up. People with narcolepsy tend to sleep about the same number of hours per day as people without, but the quality of sleep tends to be lessened.[1] The exact cause of narcolepsy is unknown, with potentially several causes.[3] In up to 10% of cases, there is a family history of the disorder. Often, those affected have low levels of the neuropeptide orexin, which may be due to an autoimmune disorder. In rare cases, narcolepsy can be caused by traumatic brain injury, tumors, or other diseases affecting the parts of the brain that regulate wakefulness or REM sleep. Diagnosis is typically based on the symptoms and sleep studies, after ruling out other potential causes. Excessive daytime sleepiness can also be caused by other sleep disorders such as sleep apnea, major depressive disorder, anemia, heart failure, drinking alcohol and not getting enough sleep. Cataplexy may be mistaken for seizures.[1] While there is no cure, a number of lifestyle changes and medications may help. Lifestyle changes include taking regular short naps and sleep hygiene. Medications used include modafinil, sodium oxybate and methylphenidate. While initially effective, tolerance to the benefits may develop over time. Tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) may improve cataplexy.[1] Estimates of frequency range from 0.2 to 600 per 100,000 people in various countries.[2] The condition often begins in childhood, with males and females being affected equally. Untreated narcolepsy increases the risk of motor vehicle collisions and falls.[1] ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Genetics * 2.2 H1N1 vaccine * 3 Pathophysiology * 3.1 Loss of neurons * 3.2 Disturbed sleep states * 4 Diagnosis * 4.1 Tests * 5 Treatment * 5.1 Antidepressants * 5.2 Children * 6 Epidemiology * 7 Society and culture * 7.1 Name * 8 Research * 8.1 Histamine-directed medications * 8.2 GABA-directed medications * 8.2.1 Flumazenil * 8.2.2 Clarithromycin * 8.3 Orexin receptor agonists * 8.4 L-carnitine * 8.5 Animal models * 8.5.1 Dog models * 8.5.2 Rodent models * 9 References * 10 External links ## Signs and symptoms[edit] There are two main characteristics of narcolepsy: excessive daytime sleepiness and abnormal REM sleep.[4] Excessive daytime sleepiness occurs even after adequate night time sleep. A person with narcolepsy is likely to become drowsy or fall asleep, often at inappropriate or undesired times and places, or just be very tired throughout the day. Narcoleptics may not be able to experience the amount of restorative deep sleep that healthy people experience due to abnormal REM regulation – they are not "over-sleeping". Narcoleptics typically have higher REM sleep density than non-narcoleptics, but also experience more REM sleep without atonia.[5] Many narcoleptics have sufficient REM sleep, but do not feel refreshed or alert throughout the day.[6] This can feel like living their entire lives in a constant state of sleep deprivation.[medical citation needed] Excessive sleepiness can vary in severity, and it appears most commonly during monotonous situations that don't require much interaction.[6] Daytime naps may occur with little warning and may be physically irresistible. These naps can occur several times a day. They are typically refreshing, but only for a few hours or less. Vivid dreams may be experienced on a regular basis, even during very brief naps. Drowsiness may persist for prolonged periods or remain constant. In addition, night-time sleep may be fragmented, with frequent awakenings. A second prominent symptom of narcolepsy is abnormal REM sleep. Narcoleptics are unique in that they enter into the REM phase of sleep in the beginnings of sleep, even when sleeping during the day.[4] The classic symptoms of the disorder, often referred to as the "tetrad of narcolepsy," are cataplexy, sleep paralysis, hypnagogic hallucinations, and excessive daytime sleepiness.[7] Other symptoms may include automatic behaviors and night-time wakefulness.[4][8][9] These symptoms may not occur in all people with narcolepsy. * Cataplexy is an episodic loss of muscle function, ranging from slight weakness such as limpness at the neck or knees, sagging facial muscles, weakness at the knees often referred to as "knee buckling",[10] or inability to speak clearly, to a complete body collapse. Episodes may be triggered by sudden emotional reactions such as laughter, anger, surprise, or fear. The person remains conscious throughout the episode. In some cases, cataplexy may resemble epileptic seizures.[11] Usually speech is slurred and vision is impaired (double vision, inability to focus), but hearing and awareness remain normal. Cataplexy also has a severe emotional impact on narcoleptics, as it can cause extreme anxiety, fear, and avoidance of people or situations that might elicit an attack. Cataplexy is generally considered to be unique to narcolepsy and is analogous to sleep paralysis in that the usually protective paralysis mechanism occurring during sleep is inappropriately activated. The opposite of this situation (failure to activate this protective paralysis) occurs in rapid eye movement behavior disorder.[medical citation needed] * Periods of wakefulness at night[4] * Sleep paralysis is the temporary inability to talk or move when waking (or less often, when falling asleep). It may last a few seconds to minutes. This is often frightening but is not dangerous.[medical citation needed] * Hypnagogic hallucinations are vivid, often frightening, dreamlike experiences that occur while dozing or falling asleep. Hypnopompic hallucinations refer to the same sensations while awakening from sleep. These hallucinations may manifest in the form of visual or auditory sensations.[4] In most cases, the first symptom of narcolepsy to appear is excessive and overwhelming daytime sleepiness. The other symptoms may begin alone or in combination months or years after the onset of the daytime naps. There are wide variations in the development, severity, and order of appearance of cataplexy, sleep paralysis, and hypnagogic hallucinations in individuals. Only about 20 to 25 percent of people with narcolepsy experience all four symptoms. The excessive daytime sleepiness generally persists throughout life, but sleep paralysis and hypnagogic hallucinations may not. Many people with narcolepsy also suffer from insomnia for extended periods of time. The excessive daytime sleepiness and cataplexy often become severe enough to cause serious problems in a person's social, personal, and professional life. Normally, when an individual is awake, brain waves show a regular rhythm. When a person first falls asleep, the brain waves become slower and less regular, which is called non-rapid eye movement (NREM) sleep. After about an hour and a half of NREM sleep, the brain waves begin to show a more active pattern again, called REM sleep (rapid eye movement sleep), when most remembered dreaming occurs. Associated with the EEG-observed waves during REM sleep, muscle atonia is present called REM atonia.[medical citation needed] In narcolepsy, the order and length of NREM and REM sleep periods are disturbed, with REM sleep occurring at sleep onset instead of after a period of NREM sleep. Also, some aspects of REM sleep that normally occur only during sleep, like lack of muscular control, sleep paralysis, and vivid dreams, occur at other times in people with narcolepsy. For example, the lack of muscular control can occur during wakefulness in a cataplexy episode; it is said that there is an intrusion of REM atonia during wakefulness. Sleep paralysis and vivid dreams can occur while falling asleep or waking up. Simply put, the brain does not pass through the normal stages of dozing and deep sleep but goes directly into (and out of) rapid eye movement (REM) sleep.[medical citation needed] As a consequence night time sleep does not include as much deep sleep, so the brain tries to "catch up" during the day, hence excessive daytime sleepiness. People with narcolepsy may visibly fall asleep at unpredicted moments (such motions as head bobbing are common). People with narcolepsy fall quickly into what appears to be very deep sleep, and they wake up suddenly and can be disoriented when they do (dizziness is a common occurrence). They have very vivid dreams, which they often remember in great detail. People with narcolepsy may dream even when they only fall asleep for a few seconds. Along with vivid dreaming, people with narcolepsy are known to have audio or visual hallucinations prior to falling asleep.[medical citation needed] Narcoleptics can gain excess weight; children can gain 20 to 40 lb (9 to 18 kg) when they first develop narcolepsy; in adults the body-mass index is about 15% above average.[12][13] ## Causes[edit] The exact cause of narcolepsy is unknown, and it may be caused by several distinct factors.[1][3] The mechanism involves the loss of orexin-releasing neurons within the lateral hypothalamus (about 70,000 neurons[14]).[15][16] In up to 10% of cases there is a family history of the disorder. Family history is more common in narcolepsy with cataplexy.[1] There is a strong link with certain genetic variants.[15] In addition to genetic factors, low levels of orexin peptides have been correlated with a past history of infection, diet, contact with toxins such as pesticides, and brain injuries due to, head trauma, brain tumors or strokes.[4][15] Autoimmunity may also play a role.[17] ### Genetics[edit] The primary genetic factor that has been strongly implicated in the development of narcolepsy involves an area of chromosome 6 known as the human leukocyte antigen (HLA) complex.[15][18] Specific variations in HLA genes are strongly correlated with the presence of narcolepsy;[15] however, these variations are not required for the condition to occur and sometimes occur in individuals without narcolepsy.[15][19] These genetic variations in the HLA complex are thought to increase the risk of an auto-immune response to orexin-releasing neurons in the lateral hypothalamus.[15][16][19] The allele HLA-DQB106:02 of the human gene HLA-DQB1 was reported in more than 90% of people with narcolepsy, and alleles of other HLA genes such as HLA-DQA101:02 have been linked. A 2009 study found a strong association with polymorphisms in the TRAC gene locus (dbSNP IDs rs1154155, rs12587781, and rs1263646).[14] A 2013 review article reported additional but weaker links to the loci of the genes TNFSF4 (rs7553711), Cathepsin H (rs34593439), and P2RY11-DNMT1 (rs2305795).[20] Another gene locus that has been associated with narcolepsy is EIF3G (rs3826784).[21] ### H1N1 vaccine[edit] A link between GlaxoSmithKline's H1N1 flu vaccine Pandemrix and narcolepsy has been found in both children and adults.[22] Finland's National Institute of Health and Welfare recommended that Pandemrix vaccinations be suspended pending further investigation into narcolepsy.[23][24] ## Pathophysiology[edit] ### Loss of neurons[edit] Orexin, otherwise known as hypocretin, is a neuropeptide that acts within the brain to regulate appetite and wakefulness as well as a number of other cognitive and physiological processes.[15][25][26] Loss of these orexin-producing neurons causes narcolepsy and most individuals with narcolepsy have a reduced number of these neurons in their brains.[15][16][19] Selective destruction of the HCRT/OX neurons with preservation of proximate structures suggests a highly specific autoimmune pathophysiology.[27] Cerebrospinal fluid HCRT-1/OX-A is undetectable in up to 95% of patients with type 1 narcolepsy.[27] The system which regulates sleep, arousal, and transitions between these states in humans is composed of three interconnected subsystems: the orexin projections from the lateral hypothalamus, the reticular activating system, and the ventrolateral preoptic nucleus.[16] In narcoleptic individuals, these systems are all associated with impairments due to a greatly reduced number of hypothalamic orexin projection neurons and significantly fewer orexin neuropeptides in cerebrospinal fluid and neural tissue, compared to non-narcoleptic individuals.[16] Those with narcolepsy generally experience the REM stage of sleep within five minutes of falling asleep, while people who do not have narcolepsy (unless they are significantly sleep deprived)[28] do not experience REM until after a period of slow-wave sleep, which lasts for about the first hour or so of a sleep cycle.[1] ### Disturbed sleep states[edit] The neural control of normal sleep states and the relationship to narcolepsy are only partially understood. In humans, narcoleptic sleep is characterized by a tendency to go abruptly from a waking state to REM sleep with little or no intervening non-REM sleep. The changes in the motor and proprioceptive systems during REM sleep have been studied in both human and animal models. During normal REM sleep, spinal and brainstem alpha motor neuron hyperpolarization produces almost complete atonia of skeletal muscles via an inhibitory descending reticulospinal pathway. Acetylcholine may be one of the neurotransmitters involved in this pathway. In narcolepsy, the reflex inhibition of the motor system seen in cataplexy has features normally seen only in normal REM sleep.[1] ## Diagnosis[edit] The third edition of the International Classification of Sleep Disorders (ICSD-3) differentiates between narcolepsy with cataplexy (type 1) and narcolepsy without cataplexy (type 2), while the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) uses the diagnosis of narcolepsy to refer to type 1 narcolepsy only. The DSM-5 refers to narcolepsy without cataplexy as hypersomnolence disorder.[29] The most recent edition of the International Classification of Diseases, ICD-11, currently identifies three types of narcolepsy: type 1 narcolepsy, type 2 narcolepsy, and unspecified narcolepsy.[30] ICSD-3 diagnostic criteria posits that the individual must experience "daily periods of irrepressible need to sleep or daytime lapses into sleep" for both subtypes of narcolepsy.[29] This symptom must last for at least three months. For a diagnosis of type 1 narcolepsy, the person must present with either cataplexy, a mean sleep latency of less than 8 minutes, and two or more sleep-onset REM periods (SOREMPs), or they must present with a hypocretin-1 concentration of less than 110 pg/mL.[29] A diagnosis of type 2 narcolepsy requires a mean sleep latency of less than 8 minutes, two or more SOREMPs, and a hypocretin-1 concentration of more than 110 pg/mL. In addition, the hypersomnolence and sleep latency findings cannot be better explained by other causes.[29] DSM-5 narcolepsy criteria requires that the person to display recurrent periods of "an irrepressible need to sleep, lapsing into sleep, or napping" for at least three times a week over a period of three months.[29] The individual must also display one of the following: cataplexy, hypocretin-1 concentration of less than 110 pg/mL, REM sleep latency of less than 15 minutes, or a multiple sleep latency test (MSLT) showing sleep latency of less than 8 minutes and two or more SOREMPs.[29] For a diagnosis of hypersomnolence disorder, the individual must present with excessive sleepiness despite at least 7 hours of sleep as well as either recurrent lapses into daytime sleep, nonrestorative sleep episodes of 9 or more hours, or difficulty staying awake after awakening. In addition, the hypersomnolence must occur at least three times a week for a period of three months, and must be accompanied by significant distress or impairment. It also cannot be explained by another sleep disorder, coexisting mental or medical disorders, or medication.[31] ### Tests[edit] Diagnosis is relatively easy when all the symptoms of narcolepsy are present, but if the sleep attacks are isolated and cataplexy is mild or absent, diagnosis is more difficult. Three tests that are commonly used in diagnosing narcolepsy are polysomnography (PSG), the multiple sleep latency test (MSLT), and the Epworth Sleepiness Scale (ESS). These tests are usually performed by a sleep specialist.[citation needed] Polysomnography involves the continuous recording of sleep brain waves and a number of nerve and muscle functions during night time sleep. When tested, people with narcolepsy fall asleep rapidly, enter REM sleep early, and may often awaken during the night. The polysomnogram also helps to detect other possible sleep disorders that could cause daytime sleepiness.[citation needed] The Epworth Sleepiness Scale is a brief questionnaire that is administered to determine the likelihood of the presence of a sleep disorder, including narcolepsy.[citation needed] The multiple sleep latency test is performed after the person undergoes an overnight sleep study. The person will be asked to sleep once every 2 hours, and the time it takes for them to do so is recorded. Most individuals will fall asleep within 5 to 8 minutes, as well as display REM sleep faster than non-narcoleptic people.[32] Measuring orexin levels in a person's cerebrospinal fluid sampled in a spinal tap may help in diagnosing narcolepsy, with abnormally low levels serving as an indicator of the disorder.[33] This test can be useful when MSLT results are inconclusive or difficult to interpret.[34] ## Treatment[edit] People with narcolepsy can be substantially helped, but not cured. However, the technology exists in early form such as experiments in using the prepro-orexin transgene via gene editing restored normal function in mice models by making other neurons produce orexin after the original set have been destroyed or replacing the missing orexinergic neurons with hypocretin stem cell transplantation are both steps in that direction for fixing the biology effectively permanently once applied in humans.[35][36] Additionally effective ideal non-gene editing and chemical-drug methods involve hypocretin treatments methods such as future drugs like hypocretin agonists (such as TAK-994) [37] which the enterprise targets it to be available by 2024 or hypocretin replacement, in the form of hypocretin 1 given intravenous (injected into the veins), intracisternal (direct injection into the brain), and intranasal (sprayed through the nose), the latter being low in efficacy, at the low amount used in current experiments but may be effective at very high doses in the future.[38][39] General strategies like people and family education, sleep hygiene and medication compliance, and discussion of safety issues for example driving license can be useful. Potential side effects of medication can also be addressed.[6] Regular follow-up is useful to be able to monitor the response to treatment, to assess the presence of other sleep disorders like obstructive sleep apnea, and to discuss psychosocial issues.[6] The main treatment of excessive daytime sleepiness in narcolepsy is central nervous system stimulants such as methylphenidate, amphetamine, dextroamphetamine, modafinil, and armodafinil. In late 2007 an alert for severe adverse skin reactions to modafinil was issued by the FDA.[40] Several studies also showed that sodium oxybate is effective to treat cataplexy.[6] Another drug that is used is atomoxetine, a non-stimulant and a norepinephrine reuptake inhibitor (NRI), which has no addiction liability or recreational effects. In many cases, planned regular short naps can reduce the need for pharmacological treatment of the EDS, but only improve symptoms for a short duration. A 120-minute nap provided benefit for 3 hours in the person's alertness whereas a 15-minute nap provided no benefit.[41] Daytime naps are not a replacement for night time sleep. Ongoing communication between the health care provider, person, and their family members is important for optimal management of narcolepsy. Another FDA-approved treatment option for narcolepsy is sodium oxybate,[42] also known as sodium gamma-hydroxybutyrate (GHB). It can be used for cataplexy associated with narcolepsy and excessive daytime sleepiness associated with narcolepsy.[42][43][6][44] Solriamfetol is a new molecule indicated for narcolespy of type 1 and 2.[45] ### Antidepressants[edit] Narcolepsy has sometimes been treated with selective serotonin reuptake inhibitors and tricyclic antidepressants, such as clomipramine, imipramine, or protriptyline, as well as other drugs that suppress REM sleep.[46] Venlafaxine, an antidepressant which blocks the reuptake of serotonin and norepinephrine, has shown usefulness in managing symptoms of cataplexy,[47] however, it has notable side-effects including sleep disruption.[48] The antidepressant class is used mainly for the treatment of cataplexy, for people with narcolepsy without cataplexy these are usually not used.[49] ### Children[edit] Common behavioral treatments for childhood narcolepsy include improved sleep hygiene, scheduled naps, and physical exercise.[50] Many medications are used in treating adults and may be used to treat childhood. These medications include central nervous system stimulants such as methylphenidate, modafinil, amphetamine, and dextroamphetamine.[51] Other medications, such as sodium oxybate[45] or atomoxetine may also be used to counteract sleepiness. Medications such as sodium oxybate, venlafaxine, fluoxetine, and clomipramine may be prescribed if the child presents with cataplexy.[52] ## Epidemiology[edit] Estimates of frequency range from 0.2 per 100,000 in Israel to 600 per 100,000 in Japan.[2] These differences may be due to how the studies were conducted or the populations themselves.[2] In the United States, narcolepsy is estimated to affect as many as 200,000 Americans, but fewer than 50,000 are diagnosed. The prevalence of narcolepsy is about 1 per 2,000 persons.[53] Narcolepsy is often mistaken for depression, epilepsy, the side effects of medications, poor sleeping habits or recreational drug use, making misdiagnosis likely.[citation needed] While narcolepsy symptoms are often confused with depression, there is a link between the two disorders. Research studies have mixed results on co-occurrence of depression in people with narcolepsy, as the numbers quoted by different studies are anywhere between 6% and 50%.[54] Narcolepsy can occur in both men and women at any age, although typical symptom onset occurs in adolescence and young adulthood. There is about a ten-year delay in diagnosing narcolepsy in adults.[13] Cognitive, educational, occupational, and psychosocial problems associated with the excessive daytime sleepiness of narcolepsy have been documented. For these to occur in the crucial teen years when education, development of self-image, and development of occupational choice are taking place is especially devastating. While cognitive impairment does occur, it may only be a reflection of the excessive daytime somnolence.[55] ## Society and culture[edit] See also: List of people with narcolepsy In 2015, it was reported that the British Department of Health was paying for sodium oxybate medication at a cost of £12,000 a year for 80 people who are taking legal action over problems linked to the use of the Pandemrix swine flu vaccine. Sodium oxybate is not available to people with narcolepsy through the National Health Service.[56] ### Name[edit] The term "narcolepsy" is from the French narcolepsie.[57] The French term was first used in 1880 by Jean-Baptiste-Édouard Gélineau, who used the Greek νάρκη (narkē), meaning "numbness", and λῆψις (lepsis) meaning "attack".[57] ## Research[edit] ### Histamine-directed medications[edit] It remains to be seen whether H3 antagonists (i.e., compounds such as pitolisant that promote the release of the wakefulness-promoting molecule amine histamine) will be particularly useful as wake-promoting agents.[58] However, usage now does exist in various nations such as in France, United Kingdom's (NHS as of September 2016[59][60][61][62]) after being given marketing authorisation by European Commission on the advice of the European Medicines Agency and in the United States by the approval of the Food and Drug Administration (FDA) as of August 2019.[63] ### GABA-directed medications[edit] Given the possible role of hyper-active GABAA receptors in the primary hypersomnias (narcolepsy and idiopathic hypersomnia), medications that could counteract this activity are being studied to test their potential to improve sleepiness. These currently include clarithromycin and flumazenil.[64][65] #### Flumazenil[edit] Flumazenil is the only GABAA receptor antagonist on the market as of Jan 2013, and it is currently manufactured only as an intravenous formulation. Given its pharmacology, researchers consider it to be a promising medication in the treatment of primary hypersomnias. Results of a small, double-blind, randomized, controlled clinical trial were published in November 2012. This research showed that flumazenil provides relief for most people whose CSF contains the unknown "somnogen" that enhances the function of GABAA receptors, making them more susceptible to the sleep-inducing effect of GABA. For one person, daily administration of flumazenil by sublingual lozenge and topical cream has proven effective for several years.[64][66] A 2014 case report also showed improvement in primary hypersomnia symptoms after treatment with a continuous subcutaneous flumazenil infusion.[67] The supply of generic flumazenil was initially thought to be too low to meet the potential demand for treatment of primary hypersomnias.[68] However, this scarcity has eased, and dozens of people are now being treated with flumazenil off-label.[69] #### Clarithromycin[edit] In a test tube model, clarithromycin (an antibiotic approved by the FDA for the treatment of infections) was found to return the function of the GABA system to normal in people with primary hypersomnias. Investigators therefore treated a few people with narcolepsy with off-label clarithromycin, and most felt their symptoms improved with this treatment. In order to help further determine whether clarithromycin is truly beneficial for the treatment of narcolepsy and idiopathic hypersomnia, a small, double-blind, randomized, controlled clinical trial was completed in 2012.[65] "In this pilot study, clarithromycin improved subjective sleepiness in GABA-related hypersomnia. Larger trials of longer duration are warranted."[70] In 2013, a retrospective review evaluating longer-term clarithromycin use showed efficacy in a large percentage of people with GABA-related hypersomnia.[71] “It is important to note that the positive effect of clarithromycin is secondary to a benzodiazepine antagonist-like effect, not its antibiotic effects, and treatment must be maintained.”[58] ### Orexin receptor agonists[edit] See also: Orexin receptor Orexin-A (a.k.a. hypocretin-1) has been shown to be strongly wake-promoting in animal models, but unfortunately it does not cross the blood-brain barrier. Therefore, companies have developed orexin receptor antagonists, like suvorexant, for the treatment of insomnia. It is also likely that an orexin-A receptor agonist will be found and developed for the treatment of hypersomnia.[58] In August 2015, Nagahara et al published their work in synthesizing the first HCRT/OX2R agonist, compound 26, with good potency and selectivity.[27] ### L-carnitine[edit] Abnormally low levels of acylcarnitine have been observed in people with narcolepsy.[72] These same low levels have been associated with primary hypersomnia in general in mouse studies. “Mice with systemic carnitine deficiency exhibit a higher frequency of fragmented wakefulness and rapid eye movement (REM) sleep, and reduced locomotor activity.” Administration of acetyl-L-carnitine was shown to improve these symptoms in mice.[73] A subsequent human trial found that people with narcolepsy given L-carnitine spent less total time in daytime sleep than people who were given a placebo.[74] ### Animal models[edit] Animal studies try to mimic the disorder in humans by either modifying the Hypocretin/Orexin receptors or by eliminating this peptide.[75] An orexin deficit caused by the degeneration of hypothalamic neurons is suggested to be one of the causes of narcolepsy.[76] More recent clinical studies on both animals and humans have also revealed that hypocretin is involved in other functions beside regulation of wakefulness and sleep. These functions include autonomic regulation, emotional processing, reward learning behaviour or energy homeostasis. In studies where the concentration of the hypocretin was measured under different circumstances, it was observed that the hypocretin levels increased with the positive emotion, anger or social interaction but stayed low during sleep or during pain experience.[77] The most reliable and valid animal models developed are the canine (narcoleptic dogs) and the rodent (orexin-deficient mice) ones which helped investigating the narcolepsy and set the focus on the role of orexin in this disorder.[76] #### Dog models[edit] Dogs, as well as other species like cats or horses, can also exhibit spontaneous narcolepsy with similar symptoms as the one reported in humans. The attacks of cataplexy in dogs can involve partial or full collapse.[76] Narcolepsy with cataplexy was identified in a few breeds like Labrador retrievers or Doberman pinschers where it was investigated the possibility to inherit this disorder in the autosomal recessive mode.[78] According to [75] a reliable canine model for narcolepsy would be the one in which the narcoleptic symptoms are the result of a mutation in the gene HCRT 2. The animals affected exhibited excessive daytime sleepiness with a reduced state of vigilance and severe cataplexy resulted after palatable food and interactions with the owners or with other animals.[75] #### Rodent models[edit] Mice that are genetically engineered to lack orexin genes demonstrate many similarities to human narcolepsy. During nocturnal hours, when mice are normally present, those lacking orexin demonstrated murine cataplexy and displayed brain and muscle electrical activity similar to the activity present during REM and NREM sleep. This cataplexy is able to be triggered through social interaction, wheel running, and ultrasonic vocalizations. Upon awakening, the mice also display behavior consistent with excessive daytime sleepiness.[76] Mice models have also been used to test whether the lack of orexin neurons is correlated with narcolepsy. Mice whose orexin neurons have been ablated have shown sleep fragmentation, SOREMPs, and obesity.[76] Rat models have been used to demonstrate the association between orexin deficiency and narcoleptic symptoms. Rats who lost the majority of their orexinergic neurons exhibited multiple SOREMPs as well as less wakefulness during nocturnal hours, shortened REM latency, and brief periods of cataplexy.[76] ## References[edit] 1. ^ a b c d e f g h i j k l m n o p q r "Narcolepsy Fact Sheet". NINDS. NIH Publication No. 03-1637. Archived from the original on 27 July 2016. Retrieved 19 August 2016. 2. ^ a b c d Goswami M, Thorpy MJ, Pandi-Perumal SR (2016). 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S2CID 41039138. ## External links[edit] Classification D * ICD-10: G47.4 * ICD-9-CM: 347 * OMIM: 161400 * MeSH: D009290 * DiseasesDB: 8801 External resources * MedlinePlus: 000802 * eMedicine: neuro/522 Wikimedia Commons has media related to Narcolepsy. * "Narcolepsy Information Page". National Institute of Neurological Disorders and Stroke. * v * t * e Sleep and sleep disorders Stages of sleep cycles * Rapid eye movement (REM) * Non-rapid eye movement * Slow-wave Brain waves * Alpha wave * Beta wave * Delta wave * Gamma wave * K-complex * Mu rhythm * PGO waves * Sensorimotor rhythm * Sleep spindle * Theta wave Sleep disorders Dyssomnia * Excessive daytime sleepiness * Hypersomnia * Insomnia * Kleine–Levin syndrome * Narcolepsy * Night eating syndrome * Nocturia * Sleep apnea * Catathrenia * Central hypoventilation syndrome * Obesity hypoventilation syndrome * Obstructive sleep apnea * Periodic breathing * Sleep state misperception Circadian rhythm disorders * Advanced sleep phase disorder * Cyclic alternating pattern * Delayed sleep phase disorder * Irregular sleep–wake rhythm * Jet lag * Non-24-hour sleep–wake disorder * Shift work sleep disorder Parasomnia * Bruxism * Nightmare disorder * Night terror * Periodic limb movement disorder * Rapid eye movement sleep behavior disorder * Sleepwalking * Somniloquy Benign phenomena * Dreams * Exploding head syndrome * Hypnic jerk * Hypnagogia / Sleep onset * Hypnopompic state * Sleep paralysis * Sleep inertia * Somnolence * Nocturnal clitoral tumescence * Nocturnal penile tumescence * Nocturnal emission Treatment * Sleep diary * Sleep hygiene * Sleep induction * Hypnosis * Lullaby * Somnology * Polysomnography Other * Sleep medicine * Behavioral sleep medicine * Sleep study Daily life * Bed * Bunk bed * Daybed * Four-poster bed * Futon * Hammock * Mattress * Sleeping bag * Bed bug * Bedding * Bedroom * Bedtime * Bedtime story * Bedtime toy * Biphasic and polyphasic sleep * Chronotype * Dream diary * Microsleep * Mouth breathing * Nap * Nightwear * Power nap * Second wind * Siesta * Sleep and creativity * Sleep and learning * Sleep deprivation / Sleep debt * Sleeping while on duty * Sleepover * Snoring [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Narcolepsy	c0027404	29,108	wikipedia	https://en.wikipedia.org/wiki/Narcolepsy	2021-01-18T18:52:51	{"mesh": ["D009290"], "icd-9": ["347.0"], "icd-10": ["G47.419", "G47.41"], "wikidata": ["Q189561"]}
A number sign (#) is used with this entry because of evidence that patterned macular dystrophy-1 (MDPT1) is caused by heterozygous mutation in the photoreceptor peripherin gene (PRPH2; 179605) on chromosome 6p21. Description Patterned dystrophies of the retinal pigment epithelium (RPE) refer to a heterogeneous group of macular disorders, characterized by an abnormal accumulation of lipofuscin in the RPE. The lipofuscin is most apparent in the macular area, and its distribution can show various sizes and shapes. High inter- and intrafamilial variability has been described, and retinitis pigmentosa (RP; see 268000)-like changes have sometimes been observed in association with patterned dystrophies (summary by Vaclavik et al., 2012). Three main varieties of patterned dystrophy of the RPE have been described: reticular ('fishnet-like') dystrophy (see 179840 and 267800), macroreticular ('spider-shaped') dystrophy, and butterfly-shaped pigment dystrophy of the fovea. ### Genetic Heterogeneity of Patterned Macular Dystrophy Also see MDPT2 (608970), caused by mutation in the CTNNA1 gene (116805) on chromosome 5q31; and MDPT3 (617111), caused by mutation in the MAPKAPK3 gene (602130) on chromosome 3p21. Clinical Features Hsieh et al. (1977) described a family in which the mother had probable reticular dystrophy, whereas a daughter had macroreticular dystrophy and a son had butterfly-shaped pigment dystrophy. They questioned the previously assumed distinctness. Marmor and Byers (1977) reported 3 generations of a family with alterations in the RPE. Younger members had granular pigment dispersed beneath the fovea, while older members showed a reticular pigment pattern, similar to other pigment dystrophies. Watzke et al. (1982) reported 2 pedigrees with pattern dystrophy. They noted that onset was usually in the second or third decade with great phenotypic variability. De Jong and Delleman (1982) described 1 family with 3 different manifestations of pigment epithelial pattern dystrophy: butterfly dystrophy, reticular dystrophy, and fundus pulverulentus. All led to the same results with regard to visual acuity, visual fields, dark adaptation, electroretinogram (ERG), and electrooculogram. Inheritance was autosomal dominant. The authors suggested that the phenotypes are different expressions of the same pigment epithelial dystrophy. Giuffre and Lodato (1986) reported 3 sibs with different phenotypes. The first sib had macroreticular dystrophy associated with butterfly-shaped dystrophy in one eye and with vitelliform cyst in the other eye. The second sib showed the atrophic outcome of a vitelliform cyst with development of subretinal neovascular membranes in one eye, and a radial pigmented macular dystrophy in the other eye. The third sib had bilateral macular vitelliform lesions. Kim et al. (1995) examined 6 affected individuals over 2 generations of a large family with fundus findings consistent with patterned dystrophy of the macula. Abnormalities ranged from subtle RPE pigmentary changes with loss of the foveal reflex to widespread macular pigmentary changes and yellow deposits in the RPE associated with disciform scarring. Only 2 patients had decreased vision unilaterally due to disciform scarring, whereas the remainder were asymptomatic. Ophthalmoscopically, the peripheral retina appeared normal in all patients, but fluorescein angiography revealed a dark choroid in 2 and choroidal neovascularization in 1. On ERG, 3 patients showed normal responses, whereas 2 others showed low amplitude responses suggestive of widespread retinal dysfunction. Color contrast sensitivity testing revealed a tritan defect of varying severity in all 5 individuals and, in some, an additional mild protan defect. Daniele et al. (1996) reported 2 families in which affected members showed different patterned alterations in the RPE, suggesting that a single pathogenic mechanism is involved in several forms. Yang et al. (2004) studied a family in which 4 affected individuals spanning 2 generations had patterned macular dystrophy. The proband was a 31-year-old man with mild metamorphopsia and visual acuity of 20/25 bilaterally. Funduscopy showed a butterfly-shaped pattern dystrophy characterized by the subretinal accumulation of yellow material in the macular area. Fluorescein angiography showed typical central hypofluorescence surrounded by areas of hyperfluorescence. His 69-year-old father and a 30-year-old sister, who had no visual complaints and 20/20 vision bilaterally, showed similar findings on funduscopic examination and fluorescein angiography. An asymptomatic 29-year-old sister, whose visual acuity was 20/20 bilaterally, had a depigmented spot in the center of the fovea on funduscopy as well as a mild central hyperfluorescent defect that faded in late frames on fluorescein angiography. Vaclavik et al. (2012) described a Swiss family with patterned macular dystrophy in which 8 affected individuals spanning 3 generations exhibited high intrafamilial variability as well as variability between both eyes of the same patient. The proband was asymptomatic at age 41 years when ophthalmologic examination revealed bilateral irregular yellowish flecks in the posterior pole and bilateral foveal butterfly-shaped lesions; she was diagnosed as having multifocal patterned dystrophy simulating Stargardt disease (see 248200). At age 48, she had metamorphopsia, photophobia, and night blindness, and optical coherence tomography (OCT) showed subfoveal hyperreflective material consistent with choroidal neovascularization. The neovascularization regressed after 4 intravitreal injections of the anti-VEGF (192240) monoclonal antibody ranibizumab. The proband's 25-year-old daughter experienced night blindness, but examination demonstrated a normal retina by funduscopy and autofluorescence imaging. Full-field ERG showed a mild reduction in rod response. The proband's 43-year-old male cousin reported metamorphopsia and was found to have butterfly-pattern dystrophy in 1 eye and adult-onset foveomacular dystrophy (AOFMD; 608161) in the other. Other affected individuals in this family had been given diagnoses of 'early' or 'atrophic' age-related macular degeneration (ARMD; see 603075). Mapping In a family in which 4 affected individuals spanning 2 generations had patterned macular dystrophy, Yang et al. (2004) performed genotype analysis using the short tandem-repeat polymorphism DNA markers D6S400, D6S1582, and D6S2410 and found linkage to the RDS/peripherin locus. Molecular Genetics In affected members of families segregating butterfly dystrophy of the RPE, Nichols et al. (1993, 1993) identified heterozygous mutations in the PRPH2 gene (179605.0009-179605.0010). In 6 affected individuals over 2 generations of a large family with fundus findings consistent with patterned dystrophy of the macula, Kim et al. (1995) identified heterozygosity for a 4-bp insertion in the PRPH2 gene (179605.0013). The mutation was not found in 6 unaffected family members. In a patient diagnosed with patterned macular dystrophy, Payne et al. (1998) identified heterozygosity for a missense mutation in the PRPH2 gene (C213R; 179605.0023). In a family in which 4 affected individuals spanning 2 generations had patterned macular dystrophy mapping to the RDS/peripherin locus, Yang et al. (2004) sequenced the RDS gene and identified a heterozygous missense mutation (Y141C; 179605.0024) that segregated with disease in the family and was not found in 200 control chromosomes. Yang et al. (2004) also identified the Y141C mutation in affected members of 2 unrelated families with adult-onset foveomacular dystrophy (AOFMD; 608161). Haplotype analysis was consistent with an ancestral founder mutation in all 3 families. The authors stated that it was unclear why the Y141C mutation caused patterned macular dystrophy in 1 family and AOFMD in the other 2, and suggested that genetic modifiers or environmental influences may play a role in these phenotypic differences. In affected individuals from a Swiss family with patterned macular dystrophy who exhibited marked intrafamilial and even intraindividual phenotypic variability, Vaclavik et al. (2012) identified heterozygosity for the Y141C mutation in the RDS gene. Wang et al. (2013) identified the C213R mutation in homozygosity in a 29-year-old woman diagnosed with Leber congenital amaurosis (LCA18; see 608133); the mutation was also detected in heterozygosity in 2 family members who exhibited patterned macular dystrophy: the proband's asymptomatic 57-year-old mother, who had 20/20 visual acuity, showed florid butterfly-shaped macular pattern dystrophy as well as other retinal flecks; and her 7-year-old son, who had decreased visual acuity due to partial amblyopia, showed a miniature form of foveal butterfly-shaped macular pattern dystrophy. In another family, a 30-year-old woman with juvenile retinitis pigmentosa (see 608133) was homozygous for an L185P mutation in PRPH2 (179605.0004), whereas her asymptomatic 56-year-old father, who had normal visual acuity but patterned macular dystrophy and foveal changes on examination, was heterozygous for L185P. INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Loss of central vision \- Metamorphopsia (in some patients) \- Night blindness (in some patients) \- Photophobia (rare) \- Abnormal deposit of pigment in perifoveal retinal pigment epithelium \- Yellow pigmented material in butterfly-shaped configuration \- Linear deposition of pale material in foveal area \- Globular deposits along major vascular arcades \- Dark choroid (rare) \- Choroidal neovascularization (in some patients) \- Tritan defect on color vision testing (in some patients) \- Protan defect on color vision testing (in some patients) MISCELLANEOUS \- Onset usually in third decade of life MOLECULAR BASIS \- Caused by mutation in the peripherin 2 gene (PRPH2, 179605.0009 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	MACULAR DYSTROPHY, PATTERNED, 1	c1868569	29,109	omim	https://www.omim.org/entry/169150	2019-09-22T16:36:31	{"doid": ["0060866"], "mesh": ["C536309"], "omim": ["169150"], "orphanet": ["99001"], "synonyms": ["PATTERNED DYSTROPHY OF RETINAL PIGMENT EPITHELIUM", "Butterfly-shaped pigmentary macular dystrophy", "BUTTERFLY DYSTROPHY OF RETINAL PIGMENT EPITHELIUM", "MACULAR DYSTROPHY, BUTTERFLY-SHAPED PIGMENTARY", "Alternative titles", "Butterfly-shaped pattern dystrophy"]}
A rare otorhinolaryngological malformation characterized by the presence of a dermoid cyst, located on the dorsum of the nose, which presents a fistula, often extending to the intracranial region. Patients present a firm, slow-growing mass, which contains skin and dermal elements (including hair follicles and sebaceous glands), that do not transilluminate or compress, and may be associated with intermittent or chronic discharge of sebaceous material, soft tissue and skeletal deformity, and local infection. Meningitis, convulsions and cerebral abscess may be observed if intracranial extension exists. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Nasal dorsum fistula	None	29,110	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=141219	2021-01-23T18:29:46	{"icd-10": ["Q18.8"]}
Clear cell adenocarcinoma of ovary is a rare, malignant, epithelilal ovarian neoplasm, composed of clear, eosinophilic and hobnail cells displaying variable degrees of tubulocystic, papillary and solid histological patterns, macroscopically appearing as a typically unilateral mass in the ovary which ranges from solid to cystic. Patients are often diagnosed in early stages and usually present with pelvic pain and pressure, an abdominal mass and/or gastrointestinal problems, such as early satiety or bloating. Association with Lynch syndrome has been reported. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Clear cell adenocarcinoma of the ovary	c1518693	29,111	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=398971	2021-01-23T17:48:29	{"icd-10": ["C56"], "synonyms": ["Ovarian clear cell adenocarcinoma"]}
Machado-Joseph disease type 2 is a subtype of Machado-Joseph disease (SCA3/MJD, see this term) with intermediate severity characterized by an intermediate age of onset, cerebellar ataxia and external progressive ophthalmoplegia, with variable pyramidal and extrapyramidal signs. ## Epidemiology The prevalence of this form of MJD is not known. It is the most frequent form of SCA3 and accounts for 57% of all SCA3 cases. ## Clinical description Patients develop the disease in middle adulthood (mean age 40 years). If present, extrapyramidal and peripheral manifestations are mild. Some patients progress within 5 to 10 years to type 1 MJD (see this term) if significant extrapyramidal signs develop, or type 3 MJD (see this term) if significant peripheral signs appear. ## Etiology The disease is caused by CAG repeat expansion mutations in the ATXN3 gene (14q21). MJD follows an autosomal dominant pattern of inheritance. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Machado-Joseph disease type 2	c0751669	29,112	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=276241	2021-01-23T18:29:07	{"mesh": ["D017827"], "umls": ["C0751669"], "icd-10": ["G11.8"], "synonyms": ["SCA3, Thomas type", "Spinocerebellar ataxia, Thomas type"]}
A number sign (#) is used with this entry because of evidence that autosomal recessive congenital ichthyosis-4A (ARCI4A) is caused by homozygous or compound heterozygous mutation in the ABCA12 gene (607800) on chromosome 2q35. Mutation in the ABCA12 gene can also cause a severe, often-fatal form of congenital ichthyosis, so-called harlequin ichthyosis (ARCI4B; 242500). Description Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of disorders of keratinization characterized primarily by abnormal skin scaling over the whole body. These disorders are limited to skin, with approximately two-thirds of patients presenting severe symptoms. The main skin phenotypes are lamellar ichthyosis (LI) and nonbullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur (summary by Fischer, 2009). Neither histopathologic findings nor ultrastructural features clearly distinguish between NCIE and LI. In addition, mutations in several genes have been shown to cause both lamellar and nonbullous ichthyosiform erythrodermal phenotypes (Akiyama et al., 2003). At the First Ichthyosis Consensus Conference in Soreze in 2009, the term 'autosomal recessive congenital ichthyosis' (ARCI) was designated to encompass LI, NCIE, and harlequin ichthyosis (ARCI4B; 242500) (Oji et al., 2010). NCIE is characterized by prominent erythroderma and fine white, superficial, semiadherent scales. Most patients present with collodion membrane at birth and have palmoplantar keratoderma, often with painful fissures, digital contractures, and loss of pulp volume. In half of the cases, a nail dystrophy including ridging, subungual hyperkeratosis, or hypoplasia has been described. Ectropion, eclabium, scalp involvement, and loss of eyebrows and lashes seem to be more frequent in NCIE than in lamellar ichthyosis (summary by Fischer et al., 2000). In LI, the scales are large, adherent, dark, and pigmented with no skin erythema. Overlapping phenotypes may depend on the age of the patient and the region of the body. The terminal differentiation of the epidermis is perturbed in both forms, leading to a reduced barrier function and defects of lipid composition in the stratum corneum (summary by Lefevre et al., 2006). In later life, the skin in ARCI may have scales that cover the entire body surface, including the flexural folds, and the scales are highly variable in size and color. Erythema may be very mild and almost invisible. Some affected persons exhibit scarring alopecia, and many have secondary anhidrosis (summary by Eckl et al., 2005). For a general phenotypic description and discussion of genetic heterogeneity of autosomal recessive congenital ichthyosis, see ARCI1 (242300). Clinical Features Parmentier et al. (1996) studied 8 affected individuals from 3 consanguineous Moroccan families with congenital ichthyosis. All patients fulfilled diagnostic criteria for the lamellar form of ichthyosis: collodion baby phenotype at birth, generalized ichthyosis with involvement of the large folds, palmoplantar keratoderma, and absence of skin erythema. No major phenotypic differences were found between the families, although mild variability was observed within families regarding the extent of scaling and the consequent mechanical ectropion. None of the patients displayed extracutaneous manifestations such as spastic paraplegia, neuritis, or hepatosplenomegaly, which may occur in ichthyosis-associated disorders such as Sjogren-Larsson syndrome (270200), Refsum syndrome (266500), and Dorfman-Chanarin syndrome (275630). Mapping By genomewide linkage analysis with polymorphic microsatellite markers in 3 consanguineous Moroccan families with congenital ichthyosis, Parmentier et al. (1996) obtained a maximum 2-point lod score of 7.60 at theta = 0 with D2S137 on chromosome 2q33-q35. Parmentier et al. (1999) presented a physical map that encompassed the ICR2B locus, including the mapping of new microsatellite markers. Based on this new map, genotyping 4 additional families from Morocco and Algeria with autosomal recessive congenital ichthyosis highly suggested a reduction in size of the candidate interval. The final interval was covered by a single YAC which was 2.2 Mb long. Molecular Genetics Lefevre et al. (2003) studied 9 families with ARCI mapping to chromosome 2q33-q35, including 2 Moroccan families originally studied by Parmentier et al. (1996) and 2 Moroccan and 2 Algerian families previously studied by Parmentier et al. (1999), as well as 2 more families from Algeria and 1 from Mali. Analysis of the candidate gene ABCA12 revealed homozygosity or compound heterozygosity for 5 different missense mutations (607800.0001-607800.0005). All of the patients were born as collodion babies, and all presented generalized lamellar ichthyosis with large adherent dark pigmented scales, with ectropion and palmoplantar keratoderma, except for 1 patient with a milder form of ichthyosis who also exhibited nail involvement (607800.0005). None of the patients presented erythema or syndromic features. Genotype/Phenotype Correlations Akiyama (2010) reviewed mutations in the ABCA12 gene and stated that a total of 56 mutations had been reported in 66 ARCI families, including 48 with harlequin ichthyosis (HI), 10 with lamellar ichthyosis (LI), and 8 with ichthyosis of the congenital ichthyosiform erythroderma (CIE) type. Most of the mutations in HI patients were truncating mutations, and homozygosity or compound heterozygosity for truncating mutations in ABCA12 always resulted in the HI phenotype. In CIE families, at least 1 mutation on each allele was typically a missense mutation, and combinations of missense mutations in the first ATP-binding cassette of ABCA12 caused the LI phenotype. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Ectropion SKIN, NAILS, & HAIR Skin \- Collodion membrane at birth \- Ichthyosis, generalized, with involvement of flexural folds \- Large adherent dark pigmented scales \- Fine whitish scales (rare) \- Palmoplantar keratoderma Nails \- Clubbing (rare) \- Leukonychia (rare) MOLECULAR BASIS \- Caused by mutation in the ATP-binding cassette, subfamily A, member 12 gene (ABCA12, 607800.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	ICHTHYOSIS, CONGENITAL, AUTOSOMAL RECESSIVE 4A	c1832550	29,113	omim	https://www.omim.org/entry/601277	2019-09-22T16:15:12	{"doid": ["0060712"], "mesh": ["C537264", "D017490"], "omim": ["601277"], "icd-10": ["Q80.2"], "orphanet": ["313"], "synonyms": ["LI", "Congenital lamellar ichthyosis", "ICHTHYOSIS, LAMELLAR, 2, FORMERLY", "Alternative titles", "ICHTHYOSIS CONGENITA IIB", "Classic lamellar ichthyosis"], "genereviews": ["NBK1420"]}
Trisomy 17p is a rare chromosomal abnormality resulting from the duplication of the short arm of chromosome 17 and characterized by pre- and post-natal growth retardation, developmental delay, hypotonia, digital abnormalities, congenital heart defects, and distinctive facial features. ## Epidemiology It has been described in fewer than 15 patients. ## Clinical description Facial dysmorphism includes microcephaly, receding forehead, down-slanting palpebral fissures, ptosis, hypertelorism, low-set malformed ears, smooth philtrum, micrognathia, high-arched palate and a short broad neck. Digital abnormalities include absent fourth and fifth digits, brachydactyly and fifth finger clinodactyly. Genital hypoplasia in males and hypertrichosis are often observed. Intellectual deficit is severe to profound and the prognosis is poor. ## Etiology Trisomy 17p has been reported to be ``pure'', as the result of a de novo 17p duplication or an extra chromosome derived from the 17p arm. It can result from a recombination of a familial pericentric inversion, or from a malsegregation of a translocation, in which case trisomy 17p can be associated with monosomy of the partner chromosome. ## Diagnostic methods Diagnosis is based on standard and molecular karyotyping. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Trisomy 17p	c0795865	29,114	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=261290	2021-01-23T17:49:28	{"gard": ["5318"], "mesh": ["C538048"], "umls": ["C0795865"], "icd-10": ["Q92.2"], "synonyms": ["Dup(17p)"]}
A number sign (#) is used with this entry because of evidence that lethal congenital contracture syndrome-3 (LCCS3) can be caused by homozygous mutation in the PIP5K1C gene (606102) on chromosome 19p13. For a general phenotypic description and a discussion of genetic heterogeneity of LCCS, see LCCS1 (253310). Clinical Features Narkis et al. (2007) described a novel type of autosomal recessive lethal congenital contracture syndrome (LCCS) that, like LCCS2 (607598), was identified in an Israeli Bedouin kindred. The phenotype was similar to that of LCCS2 but lacked the distended bladder (neurogenic bladder defect). Affected individuals were born with severe multiple joint contractures with severe muscle wasting and atrophy, mainly in the legs. Death occurred minutes to hours after birth due to respiratory insufficiency. The phenotype can be distinguished from that of LCCS1 (253310) by the absence of hydrops, fractures, and multiple pterygia. Mapping Using homozygosity mapping, Narkis et al. (2007) mapped the LCCS3 phenotype to a 3.4-Mb region on chromosome 19p13. Molecular Genetics In affected members of a large 5-generation Israeli Bedouin kindred with LCCS, and in an affected individual from an unrelated family, Narkis et al. (2007) found homozygosity for the same missense mutation in the PIP5K1C gene (D253N; 606102.0001). The mutation affects a conserved residue and abolishes PIP5K1C kinase activity. INHERITANCE \- Autosomal recessive GROWTH Other \- Small or borderline to adequate size for gestational age RESPIRATORY \- Respiratory insufficiency at birth, lethal SKELETAL Limbs \- Severe multiple joint contractures MUSCLE, SOFT TISSUES \- Severe muscle wasting and atrophy, primarily in the legs MISCELLANEOUS \- Death due to respiratory insufficiency within minutes to hours after birth MOLECULAR BASIS \- Caused by mutation in the gamma type 1 phosphatidylinositol 4-phosphate 5-kinase gene (PIP5K1C, 606102.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	LETHAL CONGENITAL CONTRACTURE SYNDROME 3	c1969655	29,115	omim	https://www.omim.org/entry/611369	2019-09-22T16:03:23	{"mesh": ["C566961"], "omim": ["611369"], "orphanet": ["137783"], "synonyms": ["Alternative titles", "MULTIPLE CONTRACTURE SYNDROME, ISRAELI BEDOUIN TYPE B"]}
A number sign (#) is used with this entry because of evidence that isolated microphthalmia-7 (MCOP7) is caused by heterozygous mutation in the GDF3 gene (606522) on chromosome 12p13. For a phenotypic description and a discussion of genetic heterogeneity of isolated microphthalmia, see MCOP1 (251600). Molecular Genetics Ye et al. (2010) screened DNA samples from 449 probands with isolated microphthalmia and/or coloboma and 23 probands with skeletal or oculoskeletal phenotypes for mutations in the GDF3 gene and identified heterozygosity for missense mutations in 2 probands with unilateral microphthalmia. In 1 family, an Asian male patient and his unaffected father were both heterozygous for an L305P (606522.0002) mutation; the authors attributed the variation in phenotype to incomplete penetrance, although digenic inheritance could not be excluded. In the second family, a female patient of European ancestry was heterozygous for an R195Q (606522.0003) substitution; the mutation status of her affected mother was not reported. INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Microphthalmia, unilateral MISCELLANEOUS \- Based on report of 2 probands (last curated July 2017) \- Reduced penetrance shown in 1 family MOLECULAR BASIS \- Caused by mutation in the growth/differentiation factor-3 gene (GDF3, 606522.0002 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	MICROPHTHALMIA, ISOLATED 7	c3150969	29,116	omim	https://www.omim.org/entry/613704	2019-09-22T15:57:48	{"doid": ["0060838"], "omim": ["613704", "251600"], "orphanet": ["2542"], "synonyms": ["Isolated anophthalmia-microphthalmia syndrome", "MAC spectrum", "Microphthalmia-anophthalmia-coloboma spectrum"]}
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: "Hematoma" – news · newspapers · books · scholar · JSTOR (April 2012) (Learn how and when to remove this template message) Hematoma Other nameshaematoma Contusion (bruise), a simple form of hematoma. SpecialtyEmergency medicine A hematoma, also spelled haematoma, is a localized bleeding outside of blood vessels, due to either disease or trauma including injury or surgery[1] and may involve blood continuing to seep from broken capillaries. A hematoma is benign and is initially in liquid form spread among the tissues including in sacs between tissues where it may coagulate and solidify before blood is reabsorbed into blood vessels. An ecchymosis is a hematoma of the skin larger than 10 mm.[2] They may occur among/within many areas such as skin and other organs, connective tissues, bone, joints and muscle. A collection of blood (or even a hemorrhage) may be aggravated by anticoagulant medication (blood thinner). Blood seepage and collection of blood may occur if heparin is given via an intramuscular route; to avoid this, heparin must be given intravenously or subcutaneously. It is not to be confused with hemangioma, which is an abnormal buildup/growth of blood vessels in the skin or internal organs.[3] ## Contents * 1 Signs and symptoms * 2 Classification * 2.1 Types * 2.2 Degrees * 3 Etymology * 4 See also * 5 References * 6 External links ## Signs and symptoms[edit] Intramuscular hematoma development and progression on the vastus lateralis muscle from 6 hours after trauma to 86 hours. Some hematomas are visible under the surface of the skin (commonly called bruises) or possibly felt as masses/lumps. Lumps may be caused by the limitation of the blood to a sac, subcutaneous or intramuscular tissue space isolated by fascial planes. This is a key anatomical feature that helps prevent injuries from causing massive blood loss. In most cases the hematoma such as a sac of blood eventually dissolves; however, in some cases they may continue to grow such as due to blood seepage or show no change. If the sac of blood does not disappear, then it may need to be surgically cleaned out/repaired. The slow process of reabsorption of hematomas can allow the broken down blood cells and hemoglobin pigment to move in the connective tissue. For example, a patient who injures the base of his thumb might cause a hematoma, which will slowly move all through the finger within a week. Gravity is the main determinant of this process. Hematomas on articulations can reduce mobility of a member and present roughly the same symptoms as a fracture. In most cases, movement and exercise of the affected muscle is the best way to introduce the collection back into the bloodstream. A misdiagnosis of a hematoma in the vertebra can sometimes occur; this is correctly called a hemangioma (buildup of cells) or a benign tumor. ## Classification[edit] ### Types[edit] Intramuscular hematoma at buttocks as a result of a sports injury. L to R: Epidural Hematoma, Subdural Hematoma, and Intracranial Hematoma. * Subdermal hematoma (under the skin) * Intramuscular hematoma (inside muscle tissue) * Skull/brain: * Subgaleal hematoma – between the galea aponeurosis and periosteum * Cephalohematoma – between the periosteum and skull. Commonly caused by vacuum delivery and vertex delivery. * Epidural hematoma – between the skull and dura mater * Subdural hematoma – between the dura mater and arachnoid mater * Subarachnoid hematoma – between the arachnoid mater and pia mater (the subarachnoid space) * Othematoma – between the skin and the layers of cartilage of the ear * Breast hematoma (breast) * Perichondral hematoma (ear) * Perianal hematoma (anus) * Subungual hematoma (nail) * Rectus sheath hematoma ### Degrees[edit] * Petechiae – small pinpoint hematomas less than 3 mm in diameter * Purpura (purple) – a bruise about 3 – 5 mm in diameter, generally round in shape * Ecchymosis – subcutaneous extravasation of blood in a thin layer under the skin, i.e. bruising or "black and blue," over 1 cm in diameter[4] ## Etymology[edit] The English word "hematoma" came into use in 1826. The word derives from the Greek αἷμα haima "blood" and -ωμα -oma, a suffix forming nouns indicating a mass or tumor.[5] ## See also[edit] * Metanephric dysplastic hematoma of the sacral region ## References[edit] 1. ^ "Hematoma, toenail, gross". library.med.utah.edu. 2013. Retrieved January 18, 2013. 2. ^ "Information on Hematoma Types, Causes, and Treatments on". Emedicinehealth.com. Retrieved 2013-04-11. 3. ^ "Hemangioma". U.S. National Library of Medicine. 2016-04-05. Retrieved 2016-04-19. 4. ^ Kumar, Vinay; Abbas, Abul K.; Aster, Jon C., eds. (2017-03-28). Robbins basic pathology. Illustrated by Perkins, James A. (10th ed.). Philadelphia, Pennsylvania. p. 101. ISBN 9780323353175. OCLC 960844656. 5. ^ "hematoma". Online Etymology Dictionary. ## External links[edit] Classification D * ICD-10: M79.81 * ICD-9-CM: 729.92 * MeSH: D006406 * DiseasesDB: 5487 * Media related to Hematomas at Wikimedia Commons * v * t * e General wounds and injuries Abrasions * Abrasion * Avulsion Blisters * Blood blister * Coma blister * Delayed blister * Edema blister * Fracture blister * Friction blister * Sucking blister Bruises * Hematoma/Ecchymosis * Battle's sign * Raccoon eyes * Black eye * Subungual hematoma * Cullen's sign * Grey Turner's sign * Retroperitoneal hemorrhage Animal bites * Insect bite * Spider bite * Snakebite Other: * Ballistic trauma * Stab wound * Blunt trauma/superficial/closed * Penetrating trauma/open * Aerosol burn * Burn/Corrosion/Chemical burn * Frostbite * Occupational injuries * Traumatic amputation By region * Hand injury * Head injury * Chest trauma * Abdominal trauma * v * t * e Disorders of bleeding and clotting Coagulation · coagulopathy · Bleeding diathesis Clotting By cause * Clotting factors * Antithrombin III deficiency * Protein C deficiency * Activated protein C resistance * Protein S deficiency * Factor V Leiden * Prothrombin G20210A * Platelets * Sticky platelet syndrome * Thrombocytosis * Essential thrombocythemia * DIC * Purpura fulminans * Antiphospholipid syndrome Clots * Thrombophilia * Thrombus * Thrombosis * Virchow's triad * Trousseau sign of malignancy By site * Deep vein thrombosis * Bancroft's sign * Homans sign * Lisker's sign * Louvel's sign * Lowenberg's sign * Peabody's sign * Pratt's sign * Rose's sign * Pulmonary embolism * Renal vein thrombosis Bleeding By cause Thrombocytopenia * Thrombocytopenic purpura: ITP * Evans syndrome * TM * TTP * Upshaw–Schulman syndrome * Heparin-induced thrombocytopenia * May–Hegglin anomaly Platelet function * adhesion * Bernard–Soulier syndrome * aggregation * Glanzmann's thrombasthenia * platelet storage pool deficiency * Hermansky–Pudlak syndrome * Gray platelet syndrome Clotting factor * Hemophilia * A/VIII * B/IX * C/XI * von Willebrand disease * Hypoprothrombinemia/II * Factor VII deficiency * Factor X deficiency * Factor XII deficiency * Factor XIII deficiency * Dysfibrinogenemia * Congenital afibrinogenemia Signs and symptoms * Bleeding * Bruise * Hematoma * Petechia * Purpura * Nonthrombocytopenic purpura By site * head * Epistaxis * Hemoptysis * Intracranial hemorrhage * Hyphema * Subconjunctival hemorrhage * torso * Hemothorax * Hemopericardium * Pulmonary hematoma * abdomen * Gastrointestinal bleeding * Hemobilia * Hemoperitoneum * Hematocele * Hematosalpinx * joint * Hemarthrosis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Hematoma	c0018944	29,117	wikipedia	https://en.wikipedia.org/wiki/Hematoma	2021-01-18T18:45:38	{"mesh": ["D006406"], "icd-10": ["T14.0"], "wikidata": ["Q468787"]}
A number sign (#) is used with this entry because the Tateyama type of distal myopathy is caused by heterozygous mutation in the caveolin-3 gene (CAV3; 601253) on chromosome 3p25. Clinical Features Tateyama et al. (2002) reported a 25-year-old Japanese woman with muscle atrophy and weakness limited to the small muscles of the hands and feet. She first presented at age 12 years with heart palpitations, which reflected infrequent premature contractions, but heart function was normal. Serum creatine kinase was significantly elevated and she was noted to have atrophy of the hypothenar muscles. However, she had no difficulties in school or daily function. On presentation at age 25 with gastritis, she was again noted to have increased serum creatine kinase and was referred to neurology. Proximal muscle strength was normal, except for a mild weakness in neck flexion. The small muscles of the hands and feet were atrophic, and strength was decreased. EMG studies showed a myopathic pattern with decreased duration and amplitude in atrophied muscles. Muscle biopsy showed mild variation in fiber size, increased internal nuclei, and type 1 fiber predominance. There was decreased sarcolemmal immunostaining for dysferlin (DYSF; 603009) and caveolin-3. However, Western blot analysis showed normal levels of dysferlin, whereas caveolin-3 was almost absent. There was no family history of a similar disorder. Fulizio et al. (2005) reported a mother and daughter with distal myopathy and absence of caveolin-3 protein on skeletal muscle biopsy. They presented at ages 30 and 27 years, respectively. The mother had distal weakness and calf hypotrophy, whereas the daughter had mild distal weakness only. Muscle biopsy showed moderated myopathic changes in the mother and dystrophic changes in the daughter. Gonzalez-Perez et al. (2009) reported a Spanish family with autosomal dominant inheritance of distal myopathy and increased serum creatine kinase. The proband was a 77-year-old man who had onset in his mid-forties of distal muscle weakness and atrophy, particularly affecting the thenar and hypothenar muscles in both hands, as well as the intrinsic finger muscles. Other features included calf hypertrophy, pes cavus, and percussion-induced rapid contractions, predominantly in distal muscles of upper limbs. He had 4 affected sons, 3 of whom presented in their twenties with increased serum creatine kinase, calf hypertrophy, and pes cavus; 1 had percussion-induced rapid contractions. All later developed distal muscle weakness and atrophy affecting the hands. The fourth son, aged 33 years, had increased serum creatine kinase and pes cavus, but no evidence of motor deficit. Two granddaughters of the proband had pes cavus and increased serum creatine kinase, but no motor deficit. One had percussion-induced rapid contractions and the other had myalgias. Muscle biopsy of the proband showed slight variation in fiber size and increased number of internal nuclei, but no dystrophic changes. Caveolin-3 expression was greatly reduced in the sarcolemma, and there was a moderate reduction of dysferlin immunolabeling. Electron microscopy revealed focal loss of sarcolemma, abnormal sarcolemmal folding, absence of normal caveolae, and enlarged subsarcolemmal space with large vacuoles. Molecular Genetics In a Japanese woman with a relatively mild nonspecific sporadic distal myopathy, Tateyama et al. (2002) identified a heterozygous mutation in the CAV3 gene (R26Q; 601253.0007). In a mother and daughter with distal myopathy, Fulizio et al. (2005) identified a heterozygous mutation in the CAV3 gene (N33K; 601253.0014). In affected members of a Spanish family with distal myopathy, Gonzalez-Perez et al. (2009) identified a heterozygous R26Q mutation in the CAV3 gene. The authors emphasized the variable features in this family, such as percussion-induced rapid contractions, suggesting rippling muscle disease (RMD2; 606072). INHERITANCE \- Autosomal dominant HEAD & NECK Neck \- Neck muscle weakness (1 patient) CARDIOVASCULAR Heart \- Palpitations, benign (1 patient) SKELETAL Feet \- Pes cavus MUSCLE, SOFT TISSUES \- Muscle weakness, distal, particularly affecting the hands \- Muscle atrophy, distal, particularly affecting the hands Muscle biopsy shows variation in fiber size \- Calf hypertrophy \- Internal nuclei \- Absence of caveolin-3 staining LABORATORY ABNORMALITIES \- Increased serum creatine kinase MISCELLANEOUS \- Three families have been reported (as of December 2011) \- Onset of distal muscle weakness in adulthood (range twenties to forties), however, pes cavus or percussion-inducted contractions may be present earlier MOLECULAR BASIS \- Caused by mutation in the caveolin 3 gene (CAV3, 601253.0007 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	MYOPATHY, DISTAL, TATEYAMA TYPE	c3280443	29,118	omim	https://www.omim.org/entry/614321	2019-09-22T15:55:42	{"doid": ["0111191"], "omim": ["614321"], "orphanet": ["488650"], "synonyms": [], "genereviews": ["NBK1385"]}
Complex partial status epilepticus SpecialtyNeurology Complex partial status epilepticus (CPSE) is one of the non-convulsive forms of status epilepticus, a rare form of epilepsy defined by its recurrent nature. CPSE is characterized by seizures involving long-lasting stupor, staring and unresponsiveness.[1] Sometimes this is accompanied by motor automatisms, such as eye twitching.[2] ## Contents * 1 Diagnosis * 2 Treatment * 3 References * 4 External links ## Diagnosis[edit] As is the case with other non-convulsive status epilepticus forms, CPSE is dangerously underdiagnosed.[3] This is due to the potentially fatal yet veiled nature of the symptoms. Usually, an electroencephalogram, or EEG, is needed to confirm a neurologist's suspicions. The EEG is also needed to differentiate between absence status epilepticus (which affects the entire brain), and CPSE, which only affects one region.[4] ## Treatment[edit] Treatment is in the form of anti-epileptic drugs, such as barbiturates, benzodiazepines and topiramate. ## References[edit] 1. ^ neuro/114 at eMedicine 2. ^ Fernández-Torre JL, Gutiérrez-Pérez R, Velasco-Zarzosa M (2003). "Non-convulsive status epilepticus". Revista de Neurología (in Spanish). 37 (8): 744–52. PMID 14593634. 3. ^ Murthy JM (1 October 2003). "Nonconvulsive status epilepticus: An under diagnosed and potentially treatable condition". Neurology India. 51 (4): 453–4. PMID 14742920. 4. ^ Husain AM, Horn GJ, Jacobson MP (2003). "Non-convulsive status epilepticus: usefulness of clinical features in selecting patients for urgent EEG". J. Neurol. Neurosurg. Psychiatry. 74 (2): 189–91. doi:10.1136/jnnp.74.2.189. PMC 1738268. PMID 12531946. ## External links[edit] Classification D * ICD-10: G41.2 * MeSH: D013226 External resources * eMedicine: neuro/114 * YouTube Video of the Condition * v * t * e Seizures and epilepsy Basics * Seizure types * Aura (warning sign) * Postictal state * Epileptogenesis * Neonatal seizure * Epilepsy in children Management * Anticonvulsants * Investigations * Electroencephalography * Epileptologist Personal issues * Epilepsy and driving * Epilepsy and employment Seizure types Focal Seizures Simple partial Complex partial Gelastic seizure Epilepsy Temporal lobe epilepsy Frontal lobe epilepsy Rolandic epilepsy Nocturnal epilepsy Panayiotopoulos syndrome Vertiginous epilepsy Generalised * Tonic–clonic * Absence seizure * Atonic seizure * Automatism * Benign familial neonatal seizures * Lennox–Gastaut syndrome * Myoclonic astatic epilepsy * Epileptic spasms Status epilepticus * Epilepsia partialis continua * Complex partial status epilepticus Myoclonic epilepsy * Progressive myoclonus epilepsy * Dentatorubral–pallidoluysian atrophy * Unverricht–Lundborg disease * MERRF syndrome * Lafora disease * Juvenile myoclonic epilepsy Non-epileptic seizure * Febrile seizure * Psychogenic non-epileptic seizure Related disorders * Sudden unexpected death in epilepsy * Todd's paresis * Landau–Kleffner syndrome * Epilepsy in animals Organizations * Citizens United for Research in Epilepsy (US) * Epilepsy Action (UK) * Epilepsy Action Australia * Epilepsy Foundation (US) * Epilepsy Outlook (UK) * Epilepsy Research UK * Epilepsy Society (UK) [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Complex partial status epilepticus	c0393734	29,119	wikipedia	https://en.wikipedia.org/wiki/Complex_partial_status_epilepticus	2021-01-18T19:03:25	{"mesh": ["D013226"], "icd-10": ["G41.2"], "wikidata": ["Q5156592"]}
A number sign (#) is used with this entry because of evidence that lattice corneal dystrophy type I (LCD1) is caused by heterozygous mutation in the gene encoding keratoepithelin (TGFBI; 601692) on chromosome 5q31. Heterozygous mutation in the TGFBI gene causes several other forms of autosomal dominant corneal dystrophy. Clinical Features Frayer and Blodi (1959) described a family. Grayish lines like cotton threads are mainly limited to a zone between the center of the cornea and the periphery, usually not extending to the limbus. Rounded dots with distinct borders are scattered everywhere. The cornea between opacities is relatively clear. Visual activity is usually normal in childhood. In this and the granular type, the histologic findings are hyaline degeneration and absence of acid mucopolysaccharide deposition. The changes involve particularly the central portion of the cornea, becoming evident in adolescence and consisting of delicate, double-contoured, interdigitating, elongated deposits that form a reticular pattern in the corneal stroma. Recurrent corneal ulceration sometimes occurs. Progression to severe visual impairment by the fifth or sixth decade is the rule. No signs of systemic abnormality have been described. Klintworth (1967) presented evidence that corneal dystrophy of the lattice type is a local variety of amyloidosis. Lattice corneal dystrophy accompanied systemic amyloidosis of the Finnish type (105120). Meretoja (1973) suggested the existence of 2 and perhaps 3 distinct forms of lattice corneal dystrophy without systemic abnormality. In type I, manifestation is early, i.e., in the first or second decade. In type II, manifestation is later with reasonably good visual acuity retained until age 50 to 70. The lattice lines in type II are thicker and fewer, leaving portions of the central cornea clear, with few or no spots or crystals. Patients have fewer erosions. Type III, of more questionable distinctness, is illustrated by the case of Wolter and Henderson (1963). Waring et al. (1978) and Gorevic et al. (1984) distinguished 3 inherited forms of lattice corneal dystrophy on clinical and histologic grounds: type I, the autosomal dominant form discussed here, which is not associated with systemic amyloidosis; type II, which is associated with systemic amyloidosis (the Finnish type); and type III, the recessive form, which has an onset at age 70 to 90 years and is not associated with systemic amyloidosis (the Japanese type; 204870). The Meretoja form of lattice corneal dystrophy is part of the Finnish form of amyloidosis and is due to a specific mutation in the gelsolin gene (137350.0001). In a large multigeneration Manitoba kindred of Belgian descent, Wiens et al. (1992) demonstrated that the gene causing autosomal dominant lattice corneal dystrophy without systemic amyloidosis was not linked to the gelsolin gene. Clinical Management Dinh et al. (1999) reviewed 50 excimer laser phototherapeutic keratectomy (PTK) procedures. Preoperative diagnoses included Reis-Bucklers dystrophy (see 121900), granular dystrophy (121900), anterior basement membrane dystrophy (121820), lattice dystrophy, and Schnyder crystalline dystrophy (121800). The authors concluded that PTK can restore and preserve useful visual function for a significant period of time in patients with anterior corneal dystrophies. Even though corneal dystrophies are likely to recur eventually after PTK, successful re-treatment with PTK is possible. Mapping Stone et al. (1994) found that the gene for lattice corneal dystrophy type I maps to 5q, in the same region as the gene for granular corneal dystrophy Groenouw type I (CDGG1; 121900) and the atypical combined granular/lattice corneal dystrophy known as the Avellino form (ACD; 607541). Molecular Genetics Munier et al. (1997) established that mutation of the gene encoding keratoepithelin (601692.0003) can cause LCD1. They postulated that the mutation resulted in amyloidogenic intermediates. Kim et al. (2002) studied the molecular properties of wildtype and mutant TGFBI proteins: specifically, the arg124-to-leu (R124L; 601692.0007) (Reis-Bucklers corneal dystrophy (CDRB; 608470)), arg124-to-cys (R124C; 601692.0003) (LCD1), arg124-to-his (R124H; 601692.0004) (ACD), arg555-to-trp (R555W; 601692.0001) (CDGG1), and arg555-to-gln (R555Q; 601692.0002) (Thiel-Behnke corneal dystrophy (CDTB; 602082)) mutations commonly found in 5q31-linked corneal dystrophies. They found that the mutations did not significantly affect the fibrillar structure, interactions with other extracellular matrix proteins, or adhesion activity in cultured corneal epithelial cells. In addition, the mutations apparently produced degradation products similar to those of wildtype TGFBI. TGFBI polymerizes to form a fibrillar structure and strongly interacts with type I collagen (see 120150), laminin (see 150320), and fibronectin (135600). Mutations did not significantly affect these properties. Kim et al. (2002) concluded that mutant forms of TGFBI might require other cornea-specific factors to form the abnormal accumulations seen in 5q31-linked corneal dystrophies. In an extensively studied African American family with lattice corneal dystrophy, Klintworth et al. (2004) and Aldave et al. (2004) reported 2 heterozygous mutations in the TGFBI gene (ala546 to asp and pro551 to gln; 601692.0009). INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Polymorphic geographic deposits at Bowman's layer \- Lattice corneal dystrophy \- Recurrent corneal ulceration \- Progressive visual impairment, mild MISCELLANEOUS \- Significant phenotypic variability MOLECULAR BASIS \- Caused by mutation in the 68-kD transforming growth factor-beta-induced gene (TGFBI, 601692.0003 ) ▲ 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	CORNEAL DYSTROPHY, LATTICE TYPE I	c1690006	29,120	omim	https://www.omim.org/entry/122200	2019-09-22T16:42:52	{"doid": ["8943"], "mesh": ["C537881"], "omim": ["122200"], "orphanet": ["98964"], "synonyms": ["Alternative titles", "LCD", "LATTICE CORNEAL DYSTROPHY, TYPE I", "CDL1"]}
## Description Idiopathic generalized epilepsy is a broad term that encompasses several common seizure phenotypes, classically including childhood absence epilepsy (CAE, ECA; see 600131), juvenile absence epilepsy (JAE, EJA; see 607631), juvenile myoclonic epilepsy (JME, EJM; see 254770), and epilepsy with grand mal seizures on awakening (Commission on Classification and Terminology of the International League Against Epilepsy, 1989). These recurrent seizures occur in the absence of detectable brain lesions and/or metabolic abnormalities. Seizures are initially generalized with a bilateral, synchronous, generalized, symmetrical EEG discharge (Zara et al., 1995; Lu and Wang, 2009). See also childhood absence epilepsy (ECA1; 600131), which has also been mapped to 8q24. Of note, benign neonatal epilepsy 2 (EBN2; 121201) is caused by mutation in the KCNQ3 gene (602232) on 8q24. ### Genetic Heterogeneity of Idiopathic Generalized Epilepsy EIG1 has been mapped to chromosome 8q24. Other loci or genes associated with EIG include EIG2 (606972) on 14q23; EIG3 (608762) on 9q32; EIG4 (609750) on 10q25; EIG5 (611934) on 10p11; EIG6 (611942), caused by mutation in the CACNA1H gene (607904) on 16p; EIG7 (604827) on 15q14; EIG8 (612899), caused by mutation in the CASR gene (601199) on 3q13.3-q21; EIG9 (607682), caused by mutation in the CACNB4 gene (601949) on 2q23; EIG10 (613060), caused by mutation in the GABRD gene (137163) on 1p36; EIG11 (607628), caused by variation in the CLCN2 gene (600570) on 3q36; EIG12 (614847), caused by mutation in the SLC2A1 gene (138140) on 1p34; EIG13 (611136), caused by mutation in the GABRA1 gene (137160) on 5q34; EIG14 (616685), caused by mutation in the SLC12A5 gene (606726) on 20q12; and EIG15 (618357), caused by mutation in the RORB gene (601972) on 9q22. Diagnosis Choi et al. (2006) developed a classification tool for partial epilepsy, termed the Partial Seizure Symptom Definitions (PSSD), to more precisely phenotype individuals for genetic research in epilepsy. The PSSD includes standardized and specific definitions of 41 partial seizure symptoms within the sensory, autonomic, aphasic, psychic, and motor categories. The aim was to encourage researchers to use the PSSD to evaluate associations between partial seizure symptoms and epilepsy susceptibility genes. Other Features McCorry et al. (2006) found an association between idiopathic generalized epilepsy and type I diabetes (IDDM; 222100) in a population-based survey in the U.K. Among 518 EIG patients aged 15 to 30 years, 7 also had IDDM. In contrast, there were 465 IDDM patients among an age-matched cohort of 150,000 individuals. The findings suggested that the prevalence of IDDM is increased in patients with EIG (odds ratio of 4.4). In a population-based case-control study of 140 Icelandic children with seizures and 180 controls, Ludvigsson et al. (2006) found that migraine with aura (157300) conferred an odds ratio of 8.1 for subsequent development of unprovoked seizures. Migraine without aura did not increase the risk for seizures. The prevalence of both types of migraine was 20.2% in children with seizures and 6.9% in controls. The findings were consistent with the hypothesis that migraine with aura and migraine without aura are separate disease entities, and suggested that migraine with aura and seizures may share a common pathogenesis. Inheritance Empirical risk numbers observed in families with EIG are compatible with an oligogenic rather than a monogenic mode of inheritance. The complex pattern of inheritance in EIG suggests an interaction of several susceptibility genes, such that polymorphisms in multiple different susceptibility genes additively contribute to the disorder (Steinlein, 2004; Lu and Wang, 2009; Saint-Martin et al., 2009). Twin and family studies suggest that genetic factors play a key part in the etiology of idiopathic generalized epilepsy. Berkovic et al. (1998) studied 253 twin pairs in whom one or both had seizures. The casewise concordances for generalized epilepsies were 0.82 in monozygotic twin pairs and 0.26 in dizygotic twin pairs. Lower degrees of concordance were observed in partial epilepsies with intermediate values seen for febrile seizures. In 94% of concordant monozygotic pairs, both twins had the same major epilepsy syndrome. A multilocus model may best fit the observed familial patterns. Winawer et al. (2003) studied 84 persons from 31 families with myoclonic or absence seizures and found that 65% (20 families) were concordant for seizure type (myoclonic, absence, or both). In 2 families, all affected members had myoclonic seizures; in 12 families, all affected members had absence seizures; in 2 families, all affected members had myoclonic and absence seizures. The number of families concordant for JME was greater when compared to JAE and CAE, but not when JAE was compared to CAE. Winawer et al. (2003) concluded that there are distinct genetic effects on absence and myoclonic seizures, and suggested that examining seizure types as opposed to syndromes may be more useful in linkage studies. Winawer et al. (2005) found concordance for seizure type, either myoclonic, absence, or both, in 23 (58%) of 40 Australian families with seizures, which was significantly higher than expected by chance alone. The findings confirmed the results of Winawer et al. (2003) that there are likely distinct genetic effects on absence and myoclonic seizures. Similarly, the authors observed clustering of generalized tonic-clonic seizures in families in which members had different forms of IGE, suggesting a specific genetic influence on the occurrence of generalized tonic-clonic seizures within IGE. Mapping Zara et al. (1995) used nonparametric methods to study idiopathic generalized epilepsy in 10 affected families. They obtained evidence for involvement of a locus at 8q24, close to the marker D8S256 (p = 0.0003). Molecular Genetics By exome sequencing of 237 ion channel subunit genes in 152 individuals with idiopathic epilepsy and 139 healthy controls, Klassen et al. (2011) drew 3 major conclusions: the architecture of ion channel variation in both patients and controls consists of highly complex patterns of common and rare alleles; structural variants in both known and suspected epilepsy genes are present in otherwise healthy individuals; and individuals with epilepsy typically carry more than 1 mutation in known human epilepsy genes. This genetic heterogeneity suggested that causality in most cases cannot be assigned to any particular variant, but rather results from a personal channel variant pattern, indicating an oligogenic mechanism. Because of the overlapping voltage dependence of these channels, even noninteracting channel proteins may modulate one another to affect transmembrane potential and disease pathogenesis. ### Associations Pending Confirmation In a patient with childhood absence epilepsy evolving to juvenile myoclonic epilepsy, consistent with EIG, Moore et al. (2001) identified a de novo heterozygous variation in the JRK gene (T456M; 603210). No functional studies were reported. The authors suggested that variation in the JRK gene may be a rare cause of epilepsy. Chioza et al. (2001) provided evidence that the CACNA1A gene (601011) on chromosome 19p is involved in the etiology of IGE. They analyzed 4 single nucleotide polymorphisms (SNPs) from patients with IGE and found that 1 of them, SNP8, showed significant association with the disease. Because SNP8 is a silent polymorphism, the authors suggested that the association must be with a closely linked variant. Sander et al. (2000) and Wilkie et al. (2002) reported associations between EIG and a polymorphism in the opioid receptor Mu-1 gene OPRM1 (N40D; 600018.0001). In the study of Sander et al. (2000), the asp40 allele frequency was increased significantly in 72 German patients with IAE (frequency = 0.139) compared to controls (frequency = 0.078; p = 0.019). The authors suggested that a variant OPRM receptor may increase liability to absence seizures, perhaps via modulating other channel currents. Among 230 patients with IGE and 234 controls, Wilkie et al. (2002) found an association for the OPRM1 118G allele with IGE, most often with the GG genotype (a recessive mode of inheritance). However, separate analysis for each IGE subtype showed that there was no association of the G118 allele for a particular subtype, such as those with absence seizures. The paper of Wilkie et al. (2002) was later retracted due to genotyping errors. The corrected results showed no association between EIG and SNPs in the OPRM1 gene. For discussion of a possible association between adolescent-onset EIG and homozygosity for a 9-SNP haplotype on the ME2 gene, see 154270.0001. For discussion of a possible association between EIG and variation in the CLCN1 gene, see 118425.0021. Animal Model Toth et al. (1995) found that insertional inactivation of the mouse jrk gene resulted in handling-induced whole body jerks, generalized clonic seizures, and epileptic brain activity, a phenotype termed 'jerky.' All homozygous animals displayed seizures. Homozygotes also displayed some degree of kyphosis of the thoracic spine and were proportionate dwarfs. Approximately half died before 3 months of age. Approximately 50% of the hemizygous animals showed generalized clonic seizures. The other hemizygous animals either displayed seizures limited to the head and limbs or showed no seizure activity. There was no apparent correlation between the level of jerky mRNA and the severity of seizures in hemizygotes. History Vadlamudi et al. (2004) reviewed the copious notes of William Lennox, who studied the genetics of epilepsy (Lennox and Lennox, 1960) and first postulated a major genetic influence in idiopathic generalized epilepsies. INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Generalized seizures, recurrent \- Generalized tonic-clonic seizures \- Absence seizures \- Myoclonic seizures \- EEG shows generalized, bilateral, synchronous, symmetrical discharge \- EEG shows spike and multispike waves, 3-4 Hz MISCELLANEOUS \- Comprises several subtypes, including \- Benign neonatal familial convulsions (see 601764 , 121200 , 121201 , and 269720 ) \- Childhood absence epilepsy (ECA1 600131 , ECA2 607681 , ECA3 607682 ) \- Juvenile absence epilepsy (JAE, 607631 ) \- Juvenile myoclonic epilepsy (JME, 606904}) \- Epilepsy with grand mal seizures on awakening (EGMA, 607628 ) \- Homozygous 9-SNP haplotype in the promoter and coding region of malic enzyme 2 (ME2, 154270.0001) increases risk for IGE (odds ratio 6.1 with 95% confidence interval 2.9-12.7) MOLECULAR BASIS \- Susceptibility conferred by 9-SNP haplotype in malic enzyme 2 (ME2, 154270.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	EPILEPSY, IDIOPATHIC GENERALIZED	c0270850	29,121	omim	https://www.omim.org/entry/600669	2019-09-22T16:15:58	{"doid": ["1827"], "mesh": ["C562694"], "omim": ["600669"], "icd-10": ["G40.309", "G40.3"], "synonyms": ["Alternative titles", "IDIOPATHIC GENERALIZED EPILEPSY"]}
Digestive system melanoma refers to a melanoma starting in the stomach, intestines, salivary glands, mouth, esophagus, liver, pancreas, gallbladder, or rectum. Melanoma is a disease in which malignant (cancer) cells form in the melanocytes. Melanocytes are commonly found in the skin and are the cells that give the skin color. While it is not uncommon for melanomas to start in the skin and later spread to other parts of the body (metastasize), melanomas originating in the gastrointestinal tract are rare. The most frequently reported site is in the esophagus and anorectum. Symptoms of a digestive system melanoma may be nonspecific, including blood in the stool, stomach pain, vomiting, diarrhea, weight loss and anemia (low red blood cell count). The cause of digestive system melanoma is not well understood. Some researchers theorize that it may have originated from an undetected primary tumor. Treatment may include surgical excision of the gastrointestinal tract involved, chemotherapy, and immunotherapy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Digestive System Melanoma	c1333798	29,122	gard	https://rarediseases.info.nih.gov/diseases/10409/digestive-system-melanoma	2021-01-18T18:00:52	{"synonyms": ["Melanoma of the gastrointestinal tract", "Melanoma of the GI tract", "Malignant melanoma of the gastrointestinal tract", "primary gastrointestinal melanoma"]}
See also: Xanthelasma Xanthoma A patient's knee showing multiple xanthoma tuberosum[1] SpecialtyGastroenterology, dermatology A xanthoma (pl. xanthomas or xanthomata) (condition: xanthomatosis), from Greek ξανθός (xanthós) 'yellow', is a deposition of yellowish cholesterol-rich material that can appear anywhere in the body in various disease states.[2] They are cutaneous manifestations of lipidosis in which lipids accumulate in large foam cells within the skin.[2] They are associated with hyperlipidemias, both primary and secondary types. Tendon xanthomas are associated with type II hyperlipidemia, chronic biliary tract obstruction, primary biliary cirrhosis and the rare metabolic disease cerebrotendineous xanthomatosis. Palmar xanthomata and tuberoeruptive xanthomata (over knees and elbows) occur in type III hyperlipidemia. ## Contents * 1 Types * 1.1 Xanthelasma * 1.2 Xanthoma tuberosum * 1.3 Xanthoma tendinosum * 1.4 Eruptive xanthoma * 1.5 Xanthoma planum * 1.6 Palmar xanthoma * 1.7 Tuberoeruptive xanthoma * 1.8 Other types * 2 See also * 3 References * 4 External links ## Types[edit] ### Xanthelasma[edit] Main article: Xanthelasma Histology picture of xanthoma showing lipid-laden foam cells with large areas of cholesterol clefts, 10 × magnification, eosin and hematoxylin stain[1] A xanthelasma is a sharply demarcated yellowish collection of cholesterol underneath the skin, usually on or around the eyelids. Strictly, a xanthelasma is a distinct condition, being called a xanthoma only when becoming larger and nodular, assuming tumorous proportions.[3] Still, it is often classified simply as a subtype of xanthoma.[4] ### Xanthoma tuberosum[edit] Xanthoma tuberosum (also known as tuberous xanthoma) is characterized by xanthomas located over the joints.[2]:530 ### Xanthoma tendinosum[edit] Xanthoma tendinosum (also tendon xanthoma or tendinous xanthoma[5]) is clinically characterized by papules and nodules found in the tendons of the hands, feet, and heel.[2]:531 Also associated with familial hypercholesterolemia (FH).[6] ### Eruptive xanthoma[edit] Eruptive xanthoma (ILDS E78.220) is clinically characterized by small, yellowish-orange to reddish-brown papules surrounded by an erythematous halo that appear suddenly all over the body, especially the hands, buttocks, and the extensor surfaces of the extremities.[2]:531 It tends to be associated with elevated triglycerides [7] ### Xanthoma planum[edit] Xanthoma planum (ILDS D76.370), also known as plane xanthoma, is clinically characterized by bands or rectangular plates (macules) and plaques in the dermis spread diffusely over large areas of the body.[2]:531 ### Palmar xanthoma[edit] Palmar xanthoma is clinically characterized by yellowish plaques that involve the palms and flexural surfaces of the fingers.[2]:531 Plane xanthomas are characterised by yellowish to orange, flat macules or slightly elevated plaques, often with a central white area which may be localised or generalised. They often arise in the skin folds, especially the palmar creases. They occur in hyperlipoproteinaemia type III and type IIA, and in association with biliary cirrhosis. The presence of palmar xanthomata, like the presence of tendinous xanthomata, is indicative of hypercholesterolaemia. ### Tuberoeruptive xanthoma[edit] Tuberoeruptive xanthoma (ILDS E78.210) is clinically characterized by red papules and nodules that appear inflamed and tend to coalesce.[2]:532 Tuberous xanthomata are considered similar, and within the same disease spectrum as eruptive xanthomata.[5] ### Other types[edit] Other types of xanthoma identified in the Medical Dictionary include:[8] * Xanthoma diabeticorum: a type of eruptive xanthoma, often with severe diabetes. * Xanthoma disseminatum: a rare xanthoma consisting of non-X histiocytes on flexural (folded) surfaces, associated with diabetes insipidus. * Verrucous xanthoma, or histiocytosis Y: a papilloma of the oral mucosa and skin whereby the connective tissue under the epithelium contains histiocytes. ## See also[edit] * Xanthelasma * List of xanthoma variants associated with hyperlipoproteinemia subtypes ## References[edit] 1. ^ a b Kumar et al. Cases Journal 2008 2. ^ a b c d e f g h 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. ^ Shields, Carol; Shields, Jerry (2008). Eyelid, conjunctival, and orbital tumors: atlas and textbook. Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 978-0-7817-7578-6. 4. ^ thefreedictionary.com > xanthelasma Citing: The American Heritage Medical Dictionary Copyright 2007, 2004 and Mosby's Medical Dictionary, 8th edition. 2009 5. ^ a b Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. pp. 1415–16. ISBN 978-1-4160-2999-1. 6. ^ van den Bosch, Harrie C.M.; Vos, Louwerens D. (1998). "Achilles'-Tendon Xanthoma in Familial Hypercholesterolemia". New England Journal of Medicine. 338 (22): 1591. doi:10.1056/NEJM199805283382205. ISSN 0028-4793. PMID 9603797. 7. ^ Digby M; Belli R; McGraw T; Lee A (2011). "Eruptive xanthomas as a cutaneous manifestation of hypertriglyceridemia: a case report". J Clin Aesthet Dermatol. 4 (1): 44–6. PMC 3030216. PMID 21278899. 8. ^ "Xanthoma". Medical Dictionary - Dictionary of Medicine and Human Biology. Retrieved 2015-02-05. ## External links[edit] Classification D * ICD-10: E78.2 (ILDS E78.280), K13.4 * ICD-9-CM: 272.2 * MeSH: D014973 * DiseasesDB: 28524 * SNOMED CT: 63103006 External resources * MedlinePlus: 001447 * eMedicine: derm/461 Look up xanthoma in Wiktionary, the free dictionary. * Media related to xanthoma at Wikimedia Commons * MedlinePlus Encyclopedia: Xanthoma * v * t * e Diseases of the skin and appendages by morphology Growths Epidermal * Wart * Callus * Seborrheic keratosis * Acrochordon * Molluscum contagiosum * Actinic keratosis * Squamous-cell carcinoma * Basal-cell carcinoma * Merkel-cell carcinoma * Nevus sebaceous * Trichoepithelioma Pigmented * Freckles * Lentigo * Melasma * Nevus * Melanoma Dermal and subcutaneous * Epidermal inclusion cyst * Hemangioma * Dermatofibroma (benign fibrous histiocytoma) * Keloid * Lipoma * Neurofibroma * Xanthoma * Kaposi's sarcoma * Infantile digital fibromatosis * Granular cell tumor * Leiomyoma * Lymphangioma circumscriptum * Myxoid cyst Rashes With epidermal involvement Eczematous * Contact dermatitis * Atopic dermatitis * Seborrheic dermatitis * Stasis dermatitis * Lichen simplex chronicus * Darier's disease * Glucagonoma syndrome * Langerhans cell histiocytosis * Lichen sclerosus * Pemphigus foliaceus * Wiskott–Aldrich syndrome * Zinc deficiency Scaling * Psoriasis * Tinea (Corporis * Cruris * Pedis * Manuum * Faciei) * Pityriasis rosea * Secondary syphilis * Mycosis fungoides * Systemic lupus erythematosus * Pityriasis rubra pilaris * Parapsoriasis * Ichthyosis Blistering * Herpes simplex * Herpes zoster * Varicella * Bullous impetigo * Acute contact dermatitis * Pemphigus vulgaris * Bullous pemphigoid * Dermatitis herpetiformis * Porphyria cutanea tarda * Epidermolysis bullosa simplex Papular * Scabies * Insect bite reactions * Lichen planus * Miliaria * Keratosis pilaris * Lichen spinulosus * Transient acantholytic dermatosis * Lichen nitidus * Pityriasis lichenoides et varioliformis acuta Pustular * Acne vulgaris * Acne rosacea * Folliculitis * Impetigo * Candidiasis * Gonococcemia * Dermatophyte * Coccidioidomycosis * Subcorneal pustular dermatosis Hypopigmented * Tinea versicolor * Vitiligo * Pityriasis alba * Postinflammatory hyperpigmentation * Tuberous sclerosis * Idiopathic guttate hypomelanosis * Leprosy * Hypopigmented mycosis fungoides Without epidermal involvement Red Blanchable Erythema Generalized * Drug eruptions * Viral exanthems * Toxic erythema * Systemic lupus erythematosus Localized * Cellulitis * Abscess * Boil * Erythema nodosum * Carcinoid syndrome * Fixed drug eruption Specialized * Urticaria * Erythema (Multiforme * Migrans * Gyratum repens * Annulare centrifugum * Ab igne) Nonblanchable Purpura Macular * Thrombocytopenic purpura * Actinic/solar purpura Papular * Disseminated intravascular coagulation * Vasculitis Indurated * Scleroderma/morphea * Granuloma annulare * Lichen sclerosis et atrophicus * Necrobiosis lipoidica Miscellaneous disorders Ulcers * Hair * Telogen effluvium * Androgenic alopecia * Alopecia areata * Systemic lupus erythematosus * Tinea capitis * Loose anagen syndrome * Lichen planopilaris * Folliculitis decalvans * Acne keloidalis nuchae Nail * Onychomycosis * Psoriasis * Paronychia * Ingrown nail Mucous membrane * Aphthous stomatitis * Oral candidiasis * Lichen planus * Leukoplakia * Pemphigus vulgaris * Mucous membrane pemphigoid * Cicatricial pemphigoid * Herpesvirus * Coxsackievirus * Syphilis * Systemic histoplasmosis * Squamous-cell carcinoma * v * t * e Inborn error of lipid metabolism: dyslipidemia Hyperlipidemia * Hypercholesterolemia/Hypertriglyceridemia * Lipoprotein lipase deficiency/Type Ia * Familial apoprotein CII deficiency/Type Ib * Familial hypercholesterolemia/Type IIa * Combined hyperlipidemia/Type IIb * Familial dysbetalipoproteinemia/Type III * Familial hypertriglyceridemia/Type IV * Xanthoma/Xanthomatosis Hypolipoproteinemia Hypoalphalipoproteinemia/HDL * Lecithin cholesterol acyltransferase deficiency * Tangier disease Hypobetalipoproteinemia/LDL * Abetalipoproteinemia * Apolipoprotein B deficiency * Chylomicron retention disease Lipodystrophy * Barraquer–Simons syndrome Other * Lipomatosis * Adiposis dolorosa * Lipoid proteinosis * APOA1 familial renal 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Xanthoma	c0302314	29,123	wikipedia	https://en.wikipedia.org/wiki/Xanthoma	2021-01-18T18:48:10	{"mesh": ["D014973"], "umls": ["C0302314"], "icd-9": ["272.2"], "icd-10": ["K13.4", "E78.2"], "wikidata": ["Q1199732"]}
A number sign (#) is used with this entry because Baraitser-Winter syndrome-2 (BRWS2) is caused by heterozygous mutation in the ACTG1 gene (102560) on chromosome 17q25. For a phenotypic description and a discussion of genetic heterogeneity of Baraitser-Winter syndrome, see BRWS1 (243310). Clinical Features Riviere et al. (2012) reported 8 patients with Baraitser-Winter syndrome-2. Three of 7 of those examined had short stature; 4 of 7 had postnatal microcephaly; all 5 patients evaluated had intellectual disability; 5 of 6 had hearing loss; and 7 of 8 had seizures. Seven of 7 had trigonocephaly; 7 of 8 had hypertelorism; 7 of 7 had high-arched eyebrows; and 8 of 8 had ptosis. Five of 7 had iris or retinal coloboma and 7 of 7 patients evaluated had anterior-to-posterior gradient lissencephaly of the pachygyria or pachygyria-band type. Verloes et al. (2015) described the phenotype and neuroimaging of 42 patients with a clinical diagnosis of Baraitser-Winter syndrome, Fryns-Aftimos syndrome, or cerebrofrontofacial syndrome, and suggested that the disorder be unified under a single designation. The major clinical anomalies were striking dysmorphic facial features with hypertelorism, broad nose with large tip and prominent root, congenital nonmyopathic ptosis, ridged metopic sutures, and arched eyebrows. Iris or retinal coloboma was present in many cases, as was sensorineural deafness. Cleft lip and palate, hallux duplex, congenital heart defects, and renal tract anomalies were seen in some patients. Microcephaly developed in some patients. Nearly all patients with ACTG1 mutations and around 60% of those with ACTB mutations had some degree of pachygyria with anteroposterior severity gradient, and rarely lissencephaly or neuronal heterotopia. Reduction of shoulder girdle muscle bulk and progressive joint stiffness were common. Early muscular involvement, occasionally with congenital arthrogryposis, was present. Intellectual disability and epilepsy were variable in severity and largely correlated with central nervous system anomalies. Inheritance Riviere et al. (2012) reported that, with one exception, all patients with Baraitser-Winter syndrome have been sporadic. The only report of affected sibs involved patients 1 and 2 in the original report (Baraitser and Winter, 1988), and further analysis of phenotypic features led Riviere et al. (2012) to consider these individuals, lost to follow-up, as not having Baraitser-Winter syndrome. Molecular Genetics Riviere et al. (2012) reported 8 patients with Baraitser-Winter syndrome carrying heterozygous missense mutations in the ACTG1 gene; in 7 patients the mutation was proven to have occurred de novo. One mutation was recurrent in 3 patients, a ser-to-phe substitution at codon 155 (102560.0009). One of these 3, LP98-096, was originally reported by Baraitser and Winter (1988) as patient 3. All the others had novel missense mutations. Autosomal dominant progressive nonsyndromic hearing loss (DFNA20/26; 604717) is also caused by mutations in ACTG1, and congenital or later-onset progressive hearing loss is a common feature of Baraitser-Winter syndrome, suggesting partially overlapping pathogenic mechanisms for Baraitser-Winter syndrome and DFNA20/26. Riviere et al. (2012) suggested that Baraitser-Winter syndrome represents the severe end of a spectrum of cytoplasmic actin-associated phenotypes that begins with Baraitser-Winter syndrome and extends to nonsyndromic hearing loss. Verloes et al. (2015) described the molecular findings in 42 patients with a clinical diagnosis of BRWS, Fryns-Aftimos syndrome, or cerebrofrontofacial syndrome. Thirty-three patients had a mutation in ACTB and 9 patients had a mutation in ACTG1. Verloes et al. (2015) suggested that ACTG1 mutations may have a more central role in neuronal migration because 8 of the 9 ACTG1 patients had a migration disorder versus one-third of those carrying ACTB mutations. Verloes et al. (2015) identified several patients with BRWS-like phenotypes in whom the ACTB and ACTG1 gene screening was negative. INHERITANCE \- Autosomal dominant HEAD & NECK Head \- Trigonocephaly/metopic ridge Face \- Prominent/full/wide cheeks \- Pointed chin \- Retrognathia (in some patients) Ears \- Abnormally shaped ears \- Deafness (in some patients) Eyes \- Microphthalmia (in some patients) \- Arched eyebrows \- Long palpebral fissures \- Eye coloboma (in some patients) \- Hypertelorism/telecanthus \- Ptosis Nose \- Short, upturned nose \- Large, squared nose tip \- Prominent nasal root on profile Mouth \- Thick/prominent/everted lower lip \- Cleft lip/palate (in some patients) \- Long philtrum \- Thin upper lip \- Large mouth Neck \- Short neck (in some patients) \- Pterygium colli (in some patients) CARDIOVASCULAR Heart \- Heart defect (in some patients) SKELETAL Spine \- Kyphosis/scoliosis (in some patients) \- Pectus (in some patients) NEUROLOGIC Central Nervous System \- Enlarged ventricles (in some patients) \- Intellectual disability \- Pachygyria/lissencephaly \- Agenesis of corpus callosum (in some patients) \- Epilepsy MOLECULAR BASIS \- Caused by mutation in the gamma-1 actin gene (ACTG1, 102560.0009 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	BARAITSER-WINTER SYNDROME 2	c1855722	29,124	omim	https://www.omim.org/entry/614583	2019-09-22T15:54:51	{"doid": ["0060229"], "mesh": ["C565462"], "omim": ["614583"], "orphanet": ["2995"], "genereviews": ["NBK327153"]}
Hyperbiliverdinemia is a rare, genetic hepatic disease characterized by the presence of green coloration of the skin, urine, plasma and other body fluids (ascites, breastmilk) or parts (sclerae) due to increased serum levels of biliverdin in association with biliary obstruction and/or liver failure. Association with malnutrition, medication, and congenital biliary atresia has also been reported. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Hyperbiliverdinemia	c3279964	29,125	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=276405	2021-01-23T18:00:22	{"omim": ["614156"], "icd-10": ["K76.8"], "synonyms": ["Green jaundice"]}
Peripheral T-cell lymphoma-Not-Otherwise-Specified SpecialtyOncology Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), is a subtype of peripheral T-cell lymphoma. Peripheral T-cell lymphoma (PTCL) is defined as a diverse group of aggressive lymphomas that develop from mature-stage white blood cells called T-cells and natural killer cells (NK cells) (see figure for an overview of PTCL subtypes). PTCL is a type of non-Hodgkin's lymphoma (NHL).[1] NHL affects two particular types of white blood cells: B-cells and T-cells. PTCL specifically affects T-cells, and results when T-cells develop and grow abnormally. About 30% of PTCL-NOS cases exhibit malignant T cells that are infected with the Epstein-Barr virus (EBV). When associated with EBV, PTCL-NOS is classified as one of the Epstein-Barr virus-associated lymphoproliferative diseases (see Epstein-Barr virus-associated peripheral T cell lymphoma, not otherwise specified) but the relationship of EBV to the development and progression of Epstein-Barr virus-associated PTCL-NOS is unclear.[2] [3] PTCL-NOS, the most common subtype of PTCL, is aggressive and predominantly nodal. There are two morphologic variants: the T-zone lymphoma variant and the lymphoepithelioid cell variant.[4][5] * T-zone lymphoma is so named for its involvement in a specific area of the lymph node that consists of a dense accumulation of T-cells.[6] * Lympho-epithelioid lymphoma, also called Lennert's lymphoma, is rare and generally affects older individuals.[7] ## Treatment[edit] Currently PTCL is treated similarly to B-cell lymphomas. However, in recent years, scientists have developed techniques to better recognize the different types of lymphomas, such as PTCL. It is now understood that PTCL behaves differently from B-cell lymphomas and therapies are being developed that specifically target these types of lymphoma. Currently, however, there are no therapies approved by the US Food and Drug Administration (FDA) specifically for PTCL. Anthracycline-containing chemotherapy regimens are commonly offered as the initial therapy. Some patients may receive a stem cell transplant.[8][9][10][11][12][13][14][15] Novel approaches to the treatment of PTCL in the relapsed or refractory setting are under investigation. Pralatrexate and cerdulatinib are some of the compounds currently under investigations for the treatment of PTC. ## References[edit] 1. ^ Swerdlow SH, WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 2008 2. ^ Rezk SA, Zhao X, Weiss LM (June 2018). "Epstein - Barr virus - associated lymphoid proliferations, a 2018 update". Human Pathology. 79: 18–41. doi:10.1016/j.humpath.2018.05.020. PMID 29885408. 3. ^ Rodriguez, J.; Gutierrez, A.; Martinez-Delgado, B.; Perez-Manga, G. (2009). "Current and future aggressive peripheral T-cell lymphoma treatment paradigms, biological features and therapeutic molecular targets". Crit Rev Oncol Hematol. 71 (3): 181–198. doi:10.1016/j.critrevonc.2008.10.011. PMID 19056295. 4. ^ Vose JM (October 2008). "Peripheral T-cell non-Hodgkin's lymphoma". Hematol. Oncol. Clin. North Am. 22 (5): 997–1005, x. doi:10.1016/j.hoc.2008.07.010. PMID 18954748. 5. ^ O’Connor, Owen. Getting the Facts; Peripheral T-Cell Lymphoma. [electronic version] Retrieved May 19, 2009, from http://www.lymphoma.org/atf/cf/%7B0363CDD6-51B5-427B-BE48-E6AF871ACEC9%7D/PTCL.PDF 6. ^ Stein H, Bonk A, Tolksdorf G, Lennert K, Rodt H, Gerdes J (August 1980). "Immunohistologic analysis of the organization of normal lymphoid tissue and non-Hodgkin's lymphomas". J. Histochem. Cytochem. 28 (8): 746–60. doi:10.1177/28.8.7003001. PMID 7003001. 7. ^ Daneshbod Y (2006). "Cytologic findings of peripheral T-cell lymphoma (PTCL) with high epitheloid cell content (Lennert's lymphoma) in imprint smear. A case report". CytoJournal. 3: 3. doi:10.1186/1742-6413-3-3. PMC 1434763. PMID 16460569. 8. ^ Reimer P, Rüdiger T, Geissinger E, et al. (January 2009). "Autologous stem-cell transplantation as first-line therapy in peripheral T-cell lymphomas: results of a prospective multicenter study". J. Clin. Oncol. 27 (1): 106–13. doi:10.1200/JCO.2008.17.4870. PMID 19029417. Archived from the original on August 3, 2012. Retrieved July 6, 2011. 9. ^ Mercadal S, Briones J, Xicoy B, et al. (May 2008). "Intensive chemotherapy (high-dose CHOP/ESHAP regimen) followed by autologous stem-cell transplantation in previously untreated patients with peripheral T-cell lymphoma". Ann. Oncol. 19 (5): 958–63. doi:10.1093/annonc/mdn022. PMID 18303032. 10. ^ Rodríguez J, Conde E, Gutiérrez A, et al. (July 2007). "Frontline autologous stem cell transplantation in high-risk peripheral T-cell lymphoma: a prospective study from The Gel-Tamo Study Group". Eur. J. Haematol. 79 (1): 32–8. doi:10.1111/j.1600-0609.2007.00856.x. PMID 17598836. 11. ^ Corradini P, Tarella C, Zallio F, et al. (September 2006). "Long-term follow-up of patients with peripheral T-cell lymphomas treated up-front with high-dose chemotherapy followed by autologous stem cell transplantation". Leukemia. 20 (9): 1533–8. doi:10.1038/sj.leu.2404306. PMID 16871285. 12. ^ d’Amore F, et al. Blood. 2006;108:A401 13. ^ Gisselbrecht C, Lepage E, Molina T, et al. (May 2002). "Shortened first-line high-dose chemotherapy for patients with poor-prognosis aggressive lymphoma". J. Clin. Oncol. 20 (10): 2472–9. doi:10.1200/JCO.2002.02.125. PMID 12011124. Archived from the original on September 3, 2012. 14. ^ Deconinck E, Lamy T, Foussard C, et al. (June 2000). "Autologous stem cell transplantation for anaplastic large-cell lymphomas: results of a prospective trial". Br. J. Haematol. 109 (4): 736–42. doi:10.1046/j.1365-2141.2000.02098.x. PMID 10929023. 15. ^ Haioun C, Lepage E, Gisselbrecht C, et al. (August 2000). "Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin's lymphoma: final analysis of the prospective LNH87-2 protocol—a groupe d'Etude des lymphomes de l'Adulte study". J. Clin. Oncol. 18 (16): 3025–30. doi:10.1200/JCO.2000.18.16.3025. PMID 10944137. Archived from the original on September 6, 2012. ## External links[edit] Classification D * ICD-10: C84.4 * ICD-9-CM: 202.7 * ICD-O: M9705/3 * MeSH: D016411 * v * t * e Leukaemias, lymphomas and related disease B cell (lymphoma, leukemia) (most CD19 * CD20) By development/ marker TdT+ * ALL (Precursor B acute lymphoblastic leukemia/lymphoma) CD5+ * naive B cell (CLL/SLL) * mantle zone (Mantle cell) CD22+ * Prolymphocytic * CD11c+ (Hairy cell leukemia) CD79a+ * germinal center/follicular B cell (Follicular * Burkitt's * GCB DLBCL * Primary cutaneous follicle center lymphoma) * marginal zone/marginal zone B-cell (Splenic marginal zone * MALT * Nodal marginal zone * Primary cutaneous marginal zone lymphoma) RS (CD15+, CD30+) * Classic Hodgkin lymphoma (Nodular sclerosis) * CD20+ (Nodular lymphocyte predominant Hodgkin lymphoma) PCDs/PP (CD38+/CD138+) * see immunoproliferative immunoglobulin disorders By infection * KSHV (Primary effusion) * EBV * Lymphomatoid granulomatosis * Post-transplant lymphoproliferative disorder * Classic Hodgkin lymphoma * Burkitt's lymphoma * HCV * Splenic marginal zone lymphoma * HIV (AIDS-related lymphoma) * Helicobacter pylori (MALT lymphoma) Cutaneous * Diffuse large B-cell lymphoma * Intravascular large B-cell lymphoma * Primary cutaneous marginal zone lymphoma * Primary cutaneous immunocytoma * Plasmacytoma * Plasmacytosis * Primary cutaneous follicle center lymphoma T/NK T cell (lymphoma, leukemia) (most CD3 * CD4 * CD8) By development/ marker * TdT+: ALL (Precursor T acute lymphoblastic leukemia/lymphoma) * prolymphocyte (Prolymphocytic) * CD30+ (Anaplastic large-cell lymphoma * Lymphomatoid papulosis type A) Cutaneous MF+variants * indolent: Mycosis fungoides * Pagetoid reticulosis * Granulomatous slack skin aggressive: Sézary disease * Adult T-cell leukemia/lymphoma Non-MF * CD30-: Non-mycosis fungoides CD30− cutaneous large T-cell lymphoma * Pleomorphic T-cell lymphoma * Lymphomatoid papulosis type B * CD30+: CD30+ cutaneous T-cell lymphoma * Secondary cutaneous CD30+ large-cell lymphoma * Lymphomatoid papulosis type A Other peripheral * Hepatosplenic * Angioimmunoblastic * Enteropathy-associated T-cell lymphoma * Peripheral T-cell lymphoma not otherwise specified (Lennert lymphoma) * Subcutaneous T-cell lymphoma By infection * HTLV-1 (Adult T-cell leukemia/lymphoma) NK cell/ (most CD56) * Aggressive NK-cell leukemia * Blastic NK cell lymphoma T or NK * EBV (Extranodal NK-T-cell lymphoma/Angiocentric lymphoma) * Large granular lymphocytic leukemia Lymphoid+ myeloid * Acute biphenotypic leukaemia Lymphocytosis * Lymphoproliferative disorders (X-linked lymphoproliferative disease * Autoimmune lymphoproliferative syndrome) * Leukemoid reaction * Diffuse infiltrative lymphocytosis syndrome Cutaneous lymphoid hyperplasia * Cutaneous lymphoid hyperplasia * with bandlike and perivascular patterns * with nodular pattern * Jessner lymphocytic infiltrate of the skin General * Hematological malignancy * leukemia * Lymphoproliferative disorders * Lymphoid leukemias [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Peripheral T-cell lymphoma not otherwise specified	c2853959	29,126	wikipedia	https://en.wikipedia.org/wiki/Peripheral_T-cell_lymphoma_not_otherwise_specified	2021-01-18T18:45:09	{"umls": ["C2853959"], "icd-9": ["202.7"], "icd-10": ["C84.4"], "wikidata": ["Q7168695"]}
Puberphonia (also known as mutational falsetto, functional falsetto, incomplete mutation, adolescent falsetto, or pubescent falsetto) is a functional voice disorder that is characterized by the habitual use of a high-pitched voice after puberty, hence why many refer to the disorder as resulting in a ‘falsetto’ voice.[1] The voice may also be heard as breathy, rough, and lacking in power.[2] The onset of puberphonia usually occurs in adolescence, between the ages of 11 and 15 years, at the same time as changes related to puberty are occurring.[2] This disorder usually occurs in the absence of other communication disorders. There is a higher male prevalence of puberphonia, as the voice disorder is characterized by a high pitch that would be inappropriate for the age and gender of the patient.[1] Typically, individuals with puberphonia do not present with underlying anatomical abnormalities. Instead, the disorder is usually psychogenic in nature, meaning resulting from psychological or emotional factors,[3] and stems from inappropriate use of the voice mechanism. The habitual use of a high pitch while speaking is associated with tense muscles surrounding the vocal folds.[4] Assessment and treatment of puberphonia is usually conducted by a speech-language pathologist (S-LP) or an otolaryngologist (ENT).[5][6] Puberphonia is not a disorder that is likely to go away on its own. Without treatment, the changes in the patient's voice can become permanent.[2] Treatment can involve direct voice therapy, indirect voice therapy, or audiovisual feedback.[5] ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Psychogenic causes * 2.2 Organic causes * 3 Assessment * 3.1 Patient profile * 3.2 Medical evaluation * 3.3 Behavioural evaluation * 3.4 Other evaluations * 4 Treatment * 4.1 Direct voice therapy * 4.2 Indirect voice therapy * 4.3 Audiovisual feedback * 4.4 Surgery * 5 Epidemiology * 6 References * 7 External links ## Signs and symptoms[edit] The laryngeal prominence, commonly known as the Adam's Apple. During puberty, changes in the larynx typically result in a decrease in pitch in both males and females. On average, the male voice deepens by one octave while the female voice lowers by a few semitones.[7] The fundamental frequency (pitch) of an adult female typically falls between 165 and 255 Hz and an adult male between 85 and 180 Hz.[8] Anatomical changes during puberty include enlargement of the larynx for both sexes. However, the larynx descends and grows significantly larger in males which often results in a visible laryngeal prominence on the neck (Adam’s Apple).[9] Additionally, male vocal folds become longer and thicker and resonant cavities become larger.[9] These changes contribute to a deepening of the voice characteristic of pubescent males. Puberphonia is characterized by the failure to transition into the lower pitched voice of adulthood. In conjunction with an atypically high pitch, common symptoms include a weak, breathy, or hoarse voice, as well as a low vocal intensity, pitch breaks, and shallow breathing.[9][10] ## Causes[edit] There are a number of proposed causes for the development of puberphonia. The aetiology of puberphonia can be both organic (biological) or psychogenic (psychological) in nature. In males, however, organic causes are rare and psychogenic causes are more common.[11] Puberphonia is described as having three main variants, related to the level of anatomical change.[12] The most common presentation of the condition is characterized by a normal adult larynx and an increased pitch due to the vocal folds adopting the falsetto position. A second variant can occur when the laryngeal development is prolonged during puberty. Lastly, puberphonia can occur due to an incomplete transformation of the larynx into the adult form.[12] ### Psychogenic causes[edit] * Emotional stress[13] * Delayed development of secondary sex characteristics[13] * Resistance to pubertal changes[3] * Self-consciousness resulting from an early breaking of the voice[11] * Self-consciousness resulting from emerging adulthood[1] * Excessive admiration of another male or sibling[14] * Excessive maternal protection[14] ### Organic causes[edit] * Laryngeal muscle tension which then causes laryngeal elevation[12] * Muscle incoordination[15] * Congenital anomalies of the larynx[12] * Vocal fold asymmetries[12] * Unilateral vocal fold paralysis[12] * Non-fusion of the thyroid laminae. When this is the case, it is important that hypogonadism is ruled out, as this may be the cause.[12] ## Assessment[edit] To determine whether a patient presents with puberphonia, a complete voice assessment including medical and diagnostic evaluations is recommended. These assessments are performed by otorhinolaryngologists and speech-language pathologists.[6] ### Patient profile[edit] Puberphonia is most often diagnosed in adolescent or adult male patients.[16] These patients often seek referral to a voice professional because of the social consequences of speaking in the falsetto register. Because a high-pitched voice is not pathologized in women, women are less likely to be referred to clinicians to treat falsetto speech.[16] Some older adult women, however, may seek a referral for this disorder due to increasing weakness of their voice and vocal fatigue at the end of the day (these cases are often referred to as "juvenile voice" or "little girl's voice" rather than puberphonia).[4][14] ### Medical evaluation[edit] Puberphonia is a functional voice disorder[citation needed]. To rule out problems in the structure of the larynx as the cause of their voice issues, patients are often referred to otorhinolaryngologists for a physical examination of the larynx and vocal folds. Once physical pathologies are ruled out, a behavioural evaluation can occur.[6] ### Behavioural evaluation[edit] A behavioural assessment for puberphonia will consist of several types of tasks, and may include: * Examining for tension in the neck and throat: The clinician will visually examine the area around the larynx to see if the voice box sits high in the throat, and palpate the area to determine whether there is excessive muscular tension.[4] * Determining the relationship between tension and vocal pitch: The clinician will ask the patient to perform warm-up and relaxation exercises such as those listed in the Treatment section below to determine whether the patient has access to their modal voice register.[4] * Establishing vocal range: The clinician will ask the patient to produce the lowest and highest pitch that they can, and perform different speaking or singing activities at various pitches.[16] * Listening for abnormal traits: The clinician will listen for the presence of breathy voice, an indication of speech in the falsetto register, and other distortions of vocal quality.[16] * Taking aerodynamic measurements: Many individuals with puberphonia may have limited breath support caused by the thoracic or shallow breathing patterns often used to support speech in the falsetto register.[4] These symptoms are assessed using vocal tasks such as maximum phonation time and direct measures of breath support such as glottal airflow and subglottal pressure.[4][6] ### Other evaluations[edit] Clinicians can also request a self-assessment, in which the patient describes their symptoms and their effects on activities of daily living.[6] The clinician may direct this self-assessment to include the identification of personality traits that may maintain the disorder, the social and emotional consequences of the symptoms experienced, and whether the patient has any access to their modal voice register.[4][16] A complete assessment for puberphonia or any other voice disorder may require a referral to another healthcare professional, such as a psychologist or a surgeon, to determine candidacy for various treatment options.[17] ## Treatment[edit] ### Direct voice therapy[edit] This condition is most often treated using voice therapy (vocal exercises) by speech-language pathologists (SLPs) or speech therapists who have experience in treating voice disorders. The duration of treatment is commonly one to two weeks.[18] Techniques used include:[19][20][1] * Cough: The patient is asked to apply pressure on the Adam's apple and cough. This results in the shortening of the vocal folds which is the physiological mechanism that reduces pitch. The patient can thus practice voicing at a lower pitch. * Speech range masking: This procedure is based on the theory that when speaking in noisy backgrounds, people speak louder and more clearly in order to be heard. The patient practices speaking while a masking noise is playing. Then, the patient listens to a recording of his/her voice during the masking session and tries to match it without the masking. By doing this, the patient practices their 'loud and clear' voice. * Glottal attack before a vowel: A glottal attack is when the vocal folds are fully closed and then pushed open by the air pressure from breathing out or making a sound. In this technique, the patient breathes in and then makes a vowel as he/she breathes out. * Effortful closure techniques: this procedure is based on pushing, pulling, or isometric exercises to forcefully close the glottis, while the patient phonates, which effectually lowers the pitch due to the lowering of the larynx. The targeted sounds or words can then be shaped from the phonation produced during the exercises. In pushing exercises, the patient pushes against a structure (e.g., a wall) or object; in pulling exercises the patient pulls an object (e.g., a chair they are sitting on); in isometric exercises the patient holds a position (e.g., pushing hands together). Additionally, effortful closure techniques can be achieved through holding one’s breath or grunting. * Laryngeal musculature relaxation techniques: Laryngeal muscles surround the vocal folds and by relaxing them, there is reduced pressure on the vocal folds. This can be done by yawning and subsequently sighing, exaggerated chewing while speaking, and speaking or singing the 'm' sound. * Lowering of larynx to appropriate position: The larynx is lowered by the patient by putting pressure on the Adam's apple. By lowering the larynx, the vocal folds relax, and thus pitch is lowered. The patient does this while speaking to practice speaking with a lower pitch. * Humming while sliding down the scale: The patient starts humming at the highest pitch that they can reach and then keeps lowering the pitch while humming. This allows the patient to practice using a lower pitch and also to relax the laryngeal muscles. * Half swallow boom technique: The patient says 'boom' just after swallowing. This is repeated with the patient turning his/her head to either side and also while lowering the chin. After practice, the patient adds more words. This technique helps to close the vocal folds completely. ### Indirect voice therapy[edit] Indirect treatment options for puberphonia focus on creating an environment where direct treatment options will be more effective.[17] Counselling, performed by the S-LP, a psychologist, or counsellor, can help patients identify the psychological factors that contribute to their disorder and give them tools to address those factors directly.[17][4] Patients may also be educated about good vocal hygiene and how their behaviour could have long term effects on their voice.[17] ### Audiovisual feedback[edit] In puberphonia, the use of audiovisual feedback allows the patient to observe graphic and numerical representations of their voice and pitch. This allows the patient to determine an ideal pitch range based on normative data on age and gender, and incrementally work through speech tasks while working in that desired pitch range. As the patient improves, speech tasks progress to become more natural, involving tasks such as reciting automatic information, to reading, to spontaneous speech and conversation.[15] Incorporating audiovisual feedback in speech and voice therapies has been successful in intervention by improving motivation and guidance.[15] ### Surgery[edit] In some cases when traditional voice therapy is ineffective, surgical interventions are considered. This can occur in situations where intervention is delayed or the patient is in denial, causing the condition to become resistant to voice therapy.[21] There are different types of surgical interventions which have been successful in lowering the vocal pitch in men with puberphonia who had previously received ineffective voice and psychotherapy. The first surgical intervention developed, called relaxation thyroplasty or tetrusion thyroplasty, involves a bilateral excision of 2 to 3 mm vertical strips of thyroid cartilage which lowers the vocal pitch through anteroposterior relaxation and shortening of the vocal folds. It can be performed under local or general anaesthesia.[21] Relaxation thyroplasty by a medial approach is a modified approach of traditional relaxation thyroplasty. This version involves lowering the vocal pitch by creating an incision bilaterally in the thyroid lamina and then depressing the anterior segment of the thyroid cartilage.[21] A more recent, less invasive intervention is the window relaxation thyroplasty. This approach involves creating a window at the anterior commissure, which is then displaced posteriorly.[21] ## Epidemiology[edit] This section needs expansion. You can help by adding to it. (November 2018) The incidence of puberphonia in India is estimated to be about 1 in 900,000 population.[22] ## References[edit] 1. ^ a b c d author., Colton, Raymond H. (2011). Understanding voice problems : a physiological perspective for diagnosis and treatment. Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 9781609138745. OCLC 660546194. 2. ^ a b c Dagli, M; Sati, I; Acar, A; Stone, RE; Dursun, G; Eryilmaz, A (2008). "Mutational falsetto: intervention outcomes in 45 patients". The Journal of Laryngology & Otology. 122 (3): 277–281. doi:10.1017/S0022215107008791. PMID 17524172. 3. ^ a b Martin, Stephanie; Lockhart, Myra (2013). Working with Voice Disorders. New York: Speechmark Publishing Ltd. p. 37. ISBN 9780863889462. 4. ^ a b c d e f g h C., Stemple, Joseph (2014-01-28). Clinical voice pathology : theory and management. Roy, Nelson,, Klaben, Bernice (Fifth ed.). San Diego, CA. ISBN 9781597569330. OCLC 985461970. 5. ^ a b Jani, Ruotsalainen; Jaana, Sellman; Laura, Lehto; Jos, Verbeek (2008-05-01). "Systematic review of the treatment of functional dysphonia and prevention of voice disorders". Otolaryngology–Head and Neck Surgery. 138 (5): 557–565. doi:10.1016/j.otohns.2008.01.014. PMID 18439458. 6. ^ a b c d e "Voice Disorders: Assessment". American Speech-Language-Hearing Association. Retrieved 2017-11-11. 7. ^ C., Stemple, Joseph (2014). Clinical voice pathology : theory and management. Roy, Nelson,, Klaben, Bernice (Fifth ed.). San Diego, CA. ISBN 9781597565561. OCLC 985461970. 8. ^ Titze, I.R. (1994). Principles of Voice Production, Prentice Hall (currently published by NCVS.org) (pp. 188), ISBN 978-0-13-717893-3. 9. ^ a b c Aronson, Arnold Elvin; Bless, Diane M. (2009). Clinical Voice Disorders. 10. ^ The management of voice disorders. Morrison, M. D. (Murray D.) (1st ed.). London: Chapman & Hall Medical. 1994. ISBN 9781489929037. OCLC 623663763.CS1 maint: others (link) 11. ^ a b Sinha, Vikas (2012). "Efficacy of Voice therapy for treatment of Puberphonia: Review of 20 cases". World Articles in Ear, Nose and Throat. 5. 12. ^ a b c d e f g Diagnosis and treatment of voice disorders. Rubin, John S. (John Stephen). New York: Igaku-Shoin. 1995. ISBN 978-0896402768. OCLC 31903364.CS1 maint: others (link) 13. ^ a b Vaidya, Sudhakar; Vyas, G. (2006-01-01). "Puberphonia: A novel approach to treatment". Indian Journal of Otolaryngology and Head and Neck Surgery. 58 (1): 20–21. doi:10.1007/BF02907732 (inactive 2021-01-16). ISSN 0019-5421. PMC 3450609. PMID 23120229.CS1 maint: DOI inactive as of January 2021 (link) 14. ^ a b c India, Thiagarajan, Balasubramanian; Stanley Medical College Chennai (2015-03-08). Puberphonia Conservative approach A review. Otolaryngology online. OCLC 910339432. 15. ^ a b c Franca, Maria; Bass-Ringdahl, Sandie (June 2015). "A clinical demonstration of the application of audiovisual biofeedback in the treatment of puberphonia". International Journal of Pediatric Otorhinolaryngology. 79 (6): 912–920. doi:10.1016/j.ijporl.2015.04.013. PMID 25912681. 16. ^ a b c d e Voice disorders and their management. Freeman, Margaret., Fawcus, Margaret. (3rd ed.). London: Whurr. 2000. ISBN 9781861561862. OCLC 53964036.CS1 maint: others (link) 17. ^ a b c d "Voice Disorders: Treatment". American Speech-Language-Hearing Association. Retrieved 2017-11-11. 18. ^ Boone, Daniel R.; MacFarlane, Stephen C.; Von Berg, Shelley L.; Zraick, Richard I. (2010). The voice and voice therapy. Allyn & Bacon. 19. ^ Morisson, Rammage, Murray, Linda. Management of Voice Disorders. Springer-Science+Business Media, B.V. ISBN 978-1-4899-2903-7. 20. ^ Fawcus, Margaret. Voice Disorders and their Management. Springer, Boston, MA. pp. 337–355. ISBN 978-1-4899-2861-0. 21. ^ a b c d Remacle, Marc; Matar, Nayla (2010). "Relaxation Thyroplasty for Mutational Falsetto Treatment". Annals of Otology, Rhinology & Laryngology. 119 (2): 105–109. doi:10.1177/000348941011900207. PMID 20336921. S2CID 28757870. 22. ^ Banerjee AB, Eajlen D, Meohurst R, Murthy GE (1995) Puberphonia – a treatable entity. world voice congress oporto portugal ## External links[edit] * Many Puberphonia Before And After Treatment Video * Frequently Asked Questions About Voice Therapy * Voice Disorders [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Puberphonia	c0264632	29,127	wikipedia	https://en.wikipedia.org/wiki/Puberphonia	2021-01-18T19:04:08	{"umls": ["C0264632"], "wikidata": ["Q3510780"]}
Chronic myeloproliferative disorders are a group of slow-growing blood cancers in which the bone marrow makes too many abnormal red blood cells, white blood cells, or platelets, which accumulate in the blood. The type of myeloproliferative disorder is based on whether too many red blood cells, white blood cells, or platelets are being made. Sometimes the body will make too many of more than one type of blood cell, but usually one type of blood cell is affected more than the others. There are 6 types of chronic myeloproliferative disorders: chronic myelogenous leukemia (CML), polycythemia vera, primary myelofibrosis (also called chronic idiopathic myelofibrosis), essential thrombocythemia, chronic neutrophilic leukemia, and chronic eosinophilic leukemia. Chronic myeloproliferative disorders sometimes become acute leukemia, in which too many abnormal white blood cells are made. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Chronic myeloproliferative disorders	c1292778	29,128	gard	https://rarediseases.info.nih.gov/diseases/9319/chronic-myeloproliferative-disorders	2021-01-18T18:01:18	{"umls": ["C1292778"], "synonyms": []}
A rare neonatal encephalopathy characterized by alterations in mental status ranging from irritability and decreased responsiveness to coma, as well as abnormal primitive reflexes, hypotonia, seizures, and abnormalities in feeding and respiration, with an onset within the first hours of life. The condition is associated with high mortality. Long-term sequelae include a spectrum of signs and symptoms including behavioral deficits, developmental delay, learning disabilities, cognitive impairment, seizures, visual and auditory dysfunction, and cerebral palsy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Neonatal hypoxic and ischemic brain injury	c0752304	29,129	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=137577	2021-01-23T18:18:45	{"mesh": ["D020925"], "umls": ["C0752304"], "icd-10": ["P91.6"], "synonyms": ["HIE", "Hypoxic and ischemic brain injury in the newborn", "Hypoxic-ischemic encephalopathy", "Perinatal asphyxia", "Perinatal hypoxia"]}
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: "Undifferentiated pleomorphic sarcoma" – news · newspapers · books · scholar · JSTOR (November 2017) (Learn how and when to remove this template message) Undifferentiated pleomorphic sarcoma Other namesUPS Micrograph of undifferentiated pleomorphic sarcoma (H&E stain) SpecialtyOncology Undifferentiated pleomorphic sarcoma, previously malignant fibrous histiocytoma, is a type of cancer, namely a soft-tissue sarcoma. It is considered a diagnosis of exclusion for sarcomas that cannot be more precisely categorized.[1][2] Other sarcomas are cancers that form in bone and soft tissues, including muscle, fat, blood vessels, lymph vessels, and fibrous tissue (such as tendons and ligaments).[3] ## Contents * 1 Presentation * 2 Diagnosis * 2.1 Pathology * 3 Treatment * 4 Prognosis * 5 Epidemiology * 6 Transmission * 7 References * 8 External links ## Presentation[edit] UPS occurs most commonly in the extremities and retroperitoneum, but has been reported in other sites. Metastasis occurs most frequently in the lungs (90%), bones (8%), and liver (1%). In the extremities, it presents itself as a painless, enlarging, soft-tissue mass. ## Diagnosis[edit] It can be detected by magnetic resonance imaging (MRI), but a biopsy is required for the definitive diagnosis. MRI findings typically show a well-circumscribed mass that is dark on T1-weighted images and bright on T2-weighted images. Central necrosis is often present and identifiable by imaging, especially in larger masses. ### Pathology[edit] UPSs are, by definition, undifferentiated, meaning (as the name implies) that they do not bear a resemblance to any normal tissue. The histomorphology, otherwise, is characterized by high cellularity, marked nuclear pleomorphism, usually accompanied by abundant mitotic activity (including atypical mitoses), and a spindle cell morphology. Necrosis is common and characteristic of high-grade lesions. ## Treatment[edit] Treatment consists of surgical excision (the extent of which ranges from tumor excision to limb amputation, depending on the tumor) and in almost all cases radiation. Radiation eliminates the need for limb amputation and there is level I evidence to show that it leads to equivalent rates of survival (Rosenberg et al. NCI). Radiation may be delivered either pre-op or post-op depending on surgeon and multidisciplinary tumor board's recommendations. Radiation can be omitted for low grade, Stage I excised tumors with >1 cm margin (NCCN). Chemotherapy remains controversial in MFH. The usual site of metastatic disease is the lungs, and metastases should be resected if possible. Unresectable or inoperable lung metastasis may be treated with stereotactic body radiation therapy (SBRT) with excellent local control. However, neither surgery nor SBRT will prevent emergence of additional metastases elsewhere in the lung. Therefore, the role of chemotherapy needs to be further explored to address systemic metastasis. ## Prognosis[edit] Prognosis depends on the primary tumor grade (appearance under the microscope as judged by a pathologist), size, resectability (whether it can be completely removed surgically), and presence of metastases. The five-year survival rate is 80%. High expression levels of AMPD2 have been shown to correlate with poor patient outcome and a proliferative tumor phenotype in UPS.[4] ## Epidemiology[edit] UPS is regarded as the most common soft-tissue sarcoma of late adult life. It rarely occurs in children.[5] It occurs more often in Caucasians than in those of African or Asian descent and is a male-predominant disease, afflicting two males for every female. ## Transmission[edit] An undifferentiated pleomorphic sarcoma was transplanted from a patient to a surgeon when he injured his hand during an operation.[6] ## References[edit] 1. ^ Matushansky I, Charytonowicz E, Mills J, Siddiqi S, Hricik T, Cordon-Cardo C (August 2009). "MFH classification: differentiating undifferentiated pleomorphic sarcoma in the 21st Century". Expert Review of Anticancer Therapy. 9 (8): 1135–44. doi:10.1586/era.09.76. PMC 3000413. PMID 19671033. 2. ^ "Neoplasia". 3. ^ "What Is Cancer?". National Cancer Institute. 2007-09-17. Retrieved 2017-11-26. 4. ^ Orth MF, Gerke JS, Knösel T, Altendorf-Hofmann A, Musa J, Alba-Rubio R, et al. (February 2019). "Functional genomics identifies AMPD2 as a new prognostic marker for undifferentiated pleomorphic sarcoma". International Journal of Cancer. 144 (4): 859–867. doi:10.1002/ijc.31903. PMID 30267407. 5. ^ Alaggio R, Collini P, Randall RL, Barnette P, Million L, Coffin CM (2010). "Undifferentiated high-grade pleomorphic sarcomas in children: a clinicopathologic study of 10 cases and review of literature". Pediatric and Developmental Pathology. 13 (3): 209–17. doi:10.2350/09-07-0673-OA.1. PMID 20055602. 6. ^ Gärtner HV, Seidl C, Luckenbach C, Schumm G, Seifried E, Ritter H, Bültmann B (November 1996). "Genetic analysis of a sarcoma accidentally transplanted from a patient to a surgeon". The New England Journal of Medicine. 335 (20): 1494–6. doi:10.1056/NEJM199611143352004. PMID 8890100. ## External links[edit] Classification D * ICD-10: C49 (ILDS C49.M10) * MeSH: D051677 * DiseasesDB: 31471 External resources * eMedicine: radio/420 * 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 * 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]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Undifferentiated pleomorphic sarcoma	c0334463	29,130	wikipedia	https://en.wikipedia.org/wiki/Undifferentiated_pleomorphic_sarcoma	2021-01-18T18:58:22	{"gard": ["6963"], "mesh": ["D051677"], "icd-10": ["C49"], "orphanet": ["2023"], "wikidata": ["Q1887348"]}
Neuronal ceroid lipofuscinosis 6 (CLN6-NCL) is a rare condition that affects the nervous system. Signs and symptoms of the condition generally develop between ages 18 months and 8 years, although later onset cases have been reported. Affected people may experience loss of muscle coordination (ataxia), seizures that do not respond to medications, muscle twitches (myoclonus), visual impairment, and developmental regression (loss of previously acquired skills). It occurs predominantly in people of Portuguese, Indian, Pakistani, or Czech ancestry. CLN6-NCL is caused by changes (mutations) in the CLN6 gene and is inherited in an autosomal recessive manner. Treatment options are limited to therapies that can help relieve some of the symptoms. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Neuronal ceroid lipofuscinosis 6	c1866282	29,131	gard	https://rarediseases.info.nih.gov/diseases/1224/neuronal-ceroid-lipofuscinosis-6	2021-01-18T17:58:43	{"mesh": ["C566627"], "omim": ["601780"], "umls": ["C1866282"], "orphanet": ["228363"], "synonyms": ["CLN6", "Neuronal ceroid lipofuscinosis, Gypsy/Indian early juvenile variant", "CLN6 disease, late infantile (subtype)", "CLN6 disease, adult Kufs type A (subtype)"]}
Misophonia, translated to “hatred of sound,” is a chronic condition that causes intense emotional reactions to specific sounds. The most common triggers include those provoked by the mouth (chewing gum or food, popping lips), the nose (breathing, sniffing, and blowing) or the fingers (typing, clicking pen, drumming on the table). Reactions to the specific sound may be mild or strong and include anxiety, disgust, rage, hatred, panic, fear or a serious emotional distress with violence and suicidal thoughts. Symptoms usually start in childhood or in the early teenage years, and severity increases over time. The cause of misophonia is not yet known. Research has suggested it may relate to parts of the brain that are responsible for processing and regulating emotions. Many people with misophonia have relatives with similar symptoms. Misophonia does affect daily life, but it may be managed by combining different therapies such as sound therapy with counseling, cognitive-behavioral therapy (CBT) and exposure, and dialectical behavior therapy. Hearing plugs or aids, antidepressant medications, and an active lifestyle (to manage stress) may also be helpful. It is important to note that misophonia is not listed in any psychiatric classification systems. Some researchers believe misophonia should be considered a new mental disorder within the spectrum of obsessive-compulsive related disorders. Others think it is a feature of a broader syndrome of sensory intolerance, rather than a separate disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Misophonia	c4324623	29,132	gard	https://rarediseases.info.nih.gov/diseases/12058/misophonia	2021-01-18T17:59:02	{"synonyms": ["Selective sound sensitivity syndrome"]}
Mammary analogue secretory carcinoma (MASC) (also termed MASCSG; the "SG" subscript indicates salivary gland)) is a salivary gland neoplasm that shares a genetic mutation with certain types of breast cancer. MASCSG was first described by Skálová et al. in 2010.[1] The authors of this report found a chromosome translocation in certain salivary gland tumors that was identical to the (12;15)(p13;q25) fusion gene mutation found previously in secretory carcinoma, a subtype of invasive ductal carcinoma of the breast. ## Contents * 1 Fusion gene * 2 Fusion protein * 3 Clinical presentation and diagnosis * 4 Clinical course and treatment * 5 References ## Fusion gene[edit] The translocation found in MASCSG occurs between the ETV6 gene located on the short arm (designated p) of chromosome 12 at position p13.2 (i.e. 12p13.2) and the NTRK3 gene located on the long arm (designated q) of chromosome 15 at position q25.3 (i.e. 15q25.3) to create the (12;15)(p13;q25) fusion gene, ETV6-NTRK3. This mutant fusion gene also occurs in congenital fibrosarcoma, congenital mesoblastic nephroma, secretory breast cancer (also termed juvenile breast cancer), acute myelogenous leukemia, ALK-negative Inflammatory myofibroblastic tumour, and radiation-induced papillary thyroid carcinoma.[2][3][4][5][6] The MASCSG gene codes for the transcription factor protein, ETV6, which suppresses the expression of, and thereby regulates, various genes that in mice are required for normal hematopoiesis as well as the development and maintenance of the vascular network.[7] The NTRK3 gene codes for Tropomyosin receptor kinase C (also termed TrkC or TEL), the receptor for neurotrophin-3. TrkC is a RTK class VII tyrosine kinase receptor. When bound to neurotrophin-3, it becomes active as a tyrosine kinase to phosphorylate cellular proteins and thereby stimuulate cell signaling pathways that lead to cellular differentiation and growth while inhibiting cellular death. TrkC makes particularly important contributions to development of the central and peripheral nervous systems. NTRK3 forms chromosomal translation-mediated fusions with many other genes in addition to ETV6 to form fused genes that are associated with the induction of a wide range of cancers including those of the lung, thyroid gland, colon, rectum, and brain.[5] ETV6-NTRK3 fusion genes in some MASCSG disease cases display atypical exon junctions and may be associated with more tissue infiltrating disease and less favorable clinical outcomes.[6] ## Fusion protein[edit] The ETV6-NTRK3 fusion gene's product, ETV6-NTRK3 protein, contains the N-terminus of ETV6 that is responsible for its [[Dimer (chemistry)\|dimerization/ polymerization ETV6, a step required for it to inhibit transcription. The protein's C-terminus contains the C-terminus of the TrkC. The fusion protein lacks transcription regulating activity but has dysregulated, i.e., continuously active tyrosine kinase activity. In consequence of the latter effect, the fusing protein continuously stimulates pro-growth and pro-survival pathways and thereby the malignant growth of its parent cells.[5][7] ## Clinical presentation and diagnosis[edit] Mammary analogue secretory carcinoma occurs somewhat more commonly in men (male to female ratio of <1.5:1.0). Patients with this disease have a mean age of 46 years although ~12% of cases occur in pediatric patients. Individuals typically present with symptomless tumors in the parotid salivary gland (68%), buccal mucosa salivary glands (9%), submandibular salivary gland (8%) or in the small salivary glands of the lower lip (5%), upper lip (4%), and hard palate (4%). Histologically, these tumors are described as have a morphology similar to secretory breast carcinoma; they typically having one or more of the following histological patterns: microcystic, papillary-cystic, follicular, and/or solid lobular. Other histological features of these tissues include: the presence of eosinophilic secretions as detected by staining strongly for eosin Y; positive staining with periodic acid-Schiff stain (often after diastase); the presence of vesicular oval nuclei with a single small but prominent nucleolus; and the absence of basophilic Haematoxylin or zymogen granules (i.e. vesicles that store enzymes near the cell's plasma membrane).[6][8] The cited histology features are insufficient to distinguish MASCSG from other Salivary gland neoplasms such as acinic cell carcinoma, low-grade cribriform cystadenocarcinoma, and adenocarcinoma not otherwise specified. MASCSG can be distinguished from these and other histologically similar tumors by either tissue identification of a) the ETV6-NTRK3 fusion gene using Fluorescence in situ hybridization or reverse transcription polymerase chain reaction gene detection methods[9] or b) a specific pattern of marker proteins as registered using specific antibody-based detection methods, i.e. MASCSG tissue should have detectable S100 (a family of calcium binding proteins), Mammaglobin (a breast cancer marker]], Keratin 7 (an intermediate filament found in epithelial cells), GATA3 (a transcription factor and breast cancer biomarker), SOX10 (a transcription factor important in neural crest origin cells and development of the peripheral nervous system), and STAT5A (a transcription factor) but lack antibody-detectable TP63 (a transcription factor in the same family as p53) and Anoctamin-1 (a voltage sensitive calcium activated chloride channel).[10][11] ## Clinical course and treatment[edit] MASCSG is currently treated as a low-grade (i.e. Grade 1) carcinoma with an overall favorable prognosis. These cases are treated by complete surgical excision. However, the tumor does have the potential to recur locally and/or spread beyond surgically dissectible margins as well as metastasize to regional lymph nodes and distant tissues, particularly in tumors with histological features indicating a high cell growth rate potential.[6][8] One study found lymph node metastasis in 5 of 34 MASCSG patients at initial surgery for the disease; these cases, when evidencing no further spread of disease, may be treated with radiation therapy.[12] The treatment of cases with disease spreading beyond regional lymph nodes has been variable, ranging from simple excision to radical resections accompanied by adjuvant radiotherapy and/or chemotherapy, depending on the location of disease.[6][13] Mean disease-free survival for MASCSG patients has been reported to be 92 months in one study.[12] The tyrosine kinase activity of NTRK3 as well as the ETV6-NTRK3 protein is inhibited by certain tyrosine kinase inhibitory drugs such as Entrectinib and LOXO-101; this offers a potential medical intervention method using these drugs to treat aggressive MASCSG disease.[5] Indeed, one patient with extensive head and neck MASCSG disease obtained an 89% fall in tumor size when treated with entrectinib. This suppression lasted only 7 months due to the tumor's acquirement of a mutation in the ETV6-NTRK3 gene. The newly mutated gene encoded an entrectinib-reisistant ETV6-NTRK3 protein. Treatment of aggressive forms of MASCSG with NTRK3-inhibiting tyrosine kinase inhibiting drugs, perhaps with switching to another type of tyrosine kinase inhibitor drug if the tumor acquires resistance to the initial drug, is under study.[5]STARTRK-2 ## References[edit] 1. ^ Skálová A, Vanecek T, Sima R, Laco J, Weinreb I, Perez-Ordonez B, Starek I, Geierova M, Simpson RH, Passador-Santos F, Ryska A, Leivo I, Kinkor Z, Michal M (2010). "Mammary analogue secretory carcinoma of salivary glands, containing the ETV6-NTRK3 fusion gene: a hitherto undescribed salivary gland tumor entity". The American Journal of Surgical Pathology. 34 (5): 599–608. doi:10.1097/PAS.0b013e3181d9efcc. PMID 20410810. 2. ^ Tognon C, Knezevich SR, Huntsman D, Roskelley CD, Melnyk N, Mathers JA, Becker L, Carneiro F, MacPherson N, Horsman D, Poremba C, Sorensen PH (Nov 2002). "Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma". Cancer Cell. 2 (5): 367–76. doi:10.1016/S1535-6108(02)00180-0. PMID 12450792. 3. ^ Majewska H, Skálová A, Stodulski D, Klimková A, Steiner P, Stankiewicz C, Biernat W. "Mammary analogue secretory carcinoma of salivary glands: a new entity associated with ETV6 gene rearrangement." Virchows Arch. 2015 Mar;466(3):245-54. doi: 10.1007/s00428-014-1701-8. Epub 2014 Dec 12. 4. ^ Argani, P.; Fritsch, M.; Kadkol, S. S.; Schuster, A.; Beckwith, J. B.; Perlman, E. J. (2000-01-01). "Detection of the ETV6-NTRK3 chimeric RNA of infantile fibrosarcoma/cellular congenital mesoblastic nephroma in paraffin-embedded tissue: application to challenging pediatric renal stromal tumors". Modern Pathology. 13 (1): 29–36. doi:10.1038/modpathol.3880006. ISSN 0893-3952. PMID 10658907. 5. ^ a b c d e Khotskaya YB, Holla VR, Farago AF, Mills Shaw KR, Meric-Bernstam F, Hong DS (2017). "Targeting TRK family proteins in cancer". Pharmacology & Therapeutics. 173: 58–66. doi:10.1016/j.pharmthera.2017.02.006. PMID 28174090. 6. ^ a b c d e Skalova A, Michal M, Simpson RH (2017). "Newly described salivary gland tumors". Modern Pathology. 30 (s1): S27–S43. doi:10.1038/modpathol.2016.167. PMID 28060365. 7. ^ a b De Braekeleer E, Douet-Guilbert N, Morel F, Le Bris MJ, Basinko A, De Braekeleer M (2012). "ETV6 fusion genes in hematological malignancies: a review". Leukemia Research. 36 (8): 945–61. doi:10.1016/j.leukres.2012.04.010. PMID 22578774. 8. ^ a b Khalele BA (2017). "Systematic review of mammary analog secretory carcinoma of salivary glands at 7 years after description". Head & Neck. doi:10.1002/hed.24755. PMID 28370824. 9. ^ Connor A, Perez-Ordoñez B, Shago M, Skálová A, Weinreb I (2012). "Mammary analog secretory carcinoma of salivary gland origin with the ETV6 gene rearrangement by FISH: expanded morphologic and immunohistochemical spectrum of a recently described entity". The American Journal of Surgical Pathology. 36 (1): 27–34. doi:10.1097/PAS.0b013e318231542a. PMID 21989350. 10. ^ Murphy DA, Ely HA, Shoemaker R, Boomer A, Culver BP, Hoskins I, Haimes JD, Walters RD, Fernandez D, Stahl JA, Lee J, Kim KM, Lamoureux J, Christiansen J (2016). "Detecting Gene Rearrangements in Patient Populations Through a 2-Step Diagnostic Test Comprised of Rapid IHC Enrichment Followed by Sensitive Next-Generation Sequencing". Applied Immunohistochemistry & Molecular Morphology. doi:10.1097/PAI.0000000000000360. PMC 5553231. PMID 27028240. 11. ^ Skálová A, Vanecek T, Simpson RH, Laco J, Majewska H, Baneckova M, Steiner P, Michal M (2016). "Mammary Analogue Secretory Carcinoma of Salivary Glands: Molecular Analysis of 25 ETV6 Gene Rearranged Tumors With Lack of Detection of Classical ETV6-NTRK3 Fusion Transcript by Standard RT-PCR: Report of 4 Cases Harboring ETV6-X Gene Fusion". The American Journal of Surgical Pathology. 40 (1): 3–13. doi:10.1097/PAS.0000000000000537. PMID 26492182. 12. ^ a b Stevens TM, Parekh V (2016). "Mammary Analogue Secretory Carcinoma". Archives of Pathology & Laboratory Medicine. 140 (9): 997–1001. doi:10.5858/arpa.2015-0075-RS. PMID 27575269. 13. ^ Drilon A, Li G, Dogan S, Gounder M, Shen R, Arcila M, Wang L, Hyman DM, Hechtman J, Wei G, Cam NR, Christiansen J, Luo D, Maneval EC, Bauer T, Patel M, Liu SV, Ou SH, Farago A, Shaw A, Shoemaker RF, Lim J, Hornby Z, Multani P, Ladanyi M, Berger M, Katabi N, Ghossein R, Ho AL (2016). "What hides behind the MASC: clinical response and acquired resistance to entrectinib after ETV6-NTRK3 identification in a mammary analogue secretory carcinoma (MASC)". Annals of Oncology. 27 (5): 920–6. doi:10.1093/annonc/mdw042. PMC 4843186. PMID 26884591. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Mammary analogue secretory carcinoma	c4042906	29,133	wikipedia	https://en.wikipedia.org/wiki/Mammary_analogue_secretory_carcinoma	2021-01-18T19:03:50	{"mesh": ["D000069295"], "umls": ["C4042906"], "wikidata": ["Q28439793"]}
Abortion in Rhode Island is legal. On June 19, 2019, the legal right to abortion was codified into Rhode Island law by passage of the Reproductive Privacy Act.[1] 71% of Rhode Islanders were found to support passing a law to protect safe, legal abortion in an October, 2018 poll.[2] The number of abortion clinics in Rhode Island has fluctuated over the years, with five in 1982, six in 1992 and three in 2014. There were 2,990 legal abortions in 2014, and 2,649 in 2015. ## Contents * 1 Terminology * 2 Context * 3 History * 3.1 Legislative history * 3.2 Judicial history * 3.3 Clinic history * 4 Statistics * 5 Abortion rights views and activities * 5.1 Protests * 6 Footnotes * 7 References ## Terminology[edit] Main article: Abortion The abortion debate most commonly relates to the "induced abortion" of an embryo or fetus at some point in a pregnancy, which is also how the term is used in a legal sense.[note 1] Some also use the term "elective abortion", which is used in relation to a claim to an unrestricted right of a woman to an abortion, whether or not she chooses to have one. The term elective abortion or voluntary abortion describes the interruption of pregnancy before viability at the request of the woman, but not for medical reasons.[3] Anti-abortion advocates tend to use terms such as "unborn baby", "unborn child", or "pre-born child",[4][5] and see the medical terms "embryo", "zygote", and "fetus" as dehumanizing.[6][7] Both "pro-choice" and "pro-life" are examples of terms labeled as political framing: they are terms which purposely try to define their philosophies in the best possible light, while by definition attempting to describe their opposition in the worst possible light. "Pro-choice" implies that the alternative viewpoint is "anti-choice", while "pro-life" implies the alternative viewpoint is "pro-death" or "anti-life".[8] The Associated Press encourages journalists to use the terms "abortion rights" and "anti-abortion".[9] ## Context[edit] See also: Abortion in the United States Free birth control correlates to teenage girls having a fewer pregnancies and fewer abortions. A 2014 New England Journal of Medicine study found such a link. At the same time, a 2011 study by Center for Reproductive Rights and Ibis Reproductive Health also found that states with more abortion restrictions have higher rates of maternal death, higher rates of uninsured pregnant women, higher rates of infant and child deaths, higher rates of teen drug and alcohol abuse, and lower rates of cancer screening.[10] According to a 2017 report from the Center for Reproductive Rights and Ibis Reproductive Health, states that tried to pass additional constraints on a women's ability to access legal abortions had fewer policies supporting women's health, maternal health and children's health. These states also tended to resist expanding Medicaid, family leave, medical leave, and sex education in public schools.[11] According to Megan Donovan, a senior policy manager at the Guttmacher Institute, states have legislation seeking to protect a woman's right to access abortion services have the lowest rates of infant mortality in the United States.[11] Poor women in the United States had problems paying for menstrual pads and tampons in 2018 and 2019. Almost two-thirds of American women could not pay for them. These were not available through the federal Women, Infants, and Children Program (WIC).[12] Lack of menstrual supplies has an economic impact on poor women. A study in St. Louis found that 36% had to miss days of work because they lacked adequate menstrual hygiene supplies during their period. This was on top of the fact that many had other menstrual issues including bleeding, cramps and other menstrual induced health issues.[12] This state was one of a majority that taxed essential hygiene products like tampons and menstrual pads as of November 2018.[13][14][15][16] ## History[edit] ### Legislative history[edit] By the end of the 1800s, all states in the Union except Louisiana had therapeutic exceptions in their legislative bans on abortions.[17] In the 19th century, bans by state legislatures on abortion were about protecting the life of the mother given the number of deaths caused by abortions; state governments saw themselves as looking out for the lives of their citizens.[17] The state was one of ten states in 2007 to have a customary informed consent provision for abortions.[18] In 2013, state Targeted Regulation of Abortion Providers (TRAP) law applied to medication induced abortions and private doctor offices in addition to abortion clinics.[19] As of May 14, 2019, the state prohibited abortions after the fetus was viable, considered to be 24 weeks. This period uses a standard defined by the US Supreme Court in 1973 with the Roe v. Wade ruling.[20][21][22] Another provision was on the books banning abortion at 12 weeks but it was not enforceable by law.[21] In May 2019, Rhode Island's Senate Judiciary Committee considered a bill that would have allowed the right to an abortion to be codified into state law before finally rejecting it.[23][24][21] On June 19, 2019, both the Rhode Island Senate and the Rhode Island House of Representatives passed the Reproductive Privacy Act. The House voted 45-29 and the Senate voted 21-17. Governor Raimondo signed the legislation the same night. On August 27, 2019, a motion was filed in Superior Court which alleges the Reproductive Privacy Act violated Article I, Section 2 of the Rhode Island Constitution.[25] These allegations are premised on plaintiffs' argument that Article I, Section2 prohibits the General Assembly from passing any law that would grant or secure any rights relating to abortion or the funding thereof.[26] ### Judicial history[edit] Abortion laws in the U.S. before the 1973 Roe v. Wade Illegal (30) Legal in case of rape (1) Legal in case of danger to woman's health (2) Legal in case of danger to woman's health, rape or incest, or likely damaged fetus (13) Legal on request (4) [citation needed] Before the U.S. Supreme Court decision Roe v. Wade decriminalized abortion nationwide in 1973, abortion was already legal in several states, but the decision imposed a uniform framework for state legislation on the subject. It established a minimal period during which abortion is legal (with more or fewer restrictions throughout the pregnancy). That basic framework, modified in Planned Parenthood v. Casey (1992), remains nominally in place, although the effective availability of abortion varies significantly from state to state, as many counties have no abortion providers.[27] Planned Parenthood v. Casey held that a law cannot place legal restrictions imposing an undue burden for "the purpose or effect of placing a substantial obstacle in the path of a woman seeking an abortion of a nonviable fetus."[28] ### Clinic history[edit] Number of abortion clinics in Rhode Island by year. See also: Abortion clinic Between 1982 and 1992, the number of abortion clinics in the state increased by one, going from five in 1982 to 6 in 1992.[29] In 2014, there were three abortion clinics in the state.[30] In 2014, 80% of the counties in the state did not have an abortion clinic. That year, 36% of women in the state aged 15 – 44 lived in a county without an abortion clinic.[31] In 2017, there was one Planned Parenthood clinics in a state with a population of 246,389 women aged 15 – 49 of which one offered abortion services.[32] ## Statistics[edit] In the period between 1972 and 1974, there was only 0 recorded illegal abortion death in the state.[33] In 1990, 137,000 women in the state faced the risk of an unintended pregnancy.[29] In 2010, the state had 0 publicly funded abortions.[34] In 2014, 63% of adults said in a poll by the Pew Research Center that abortion should be legal in all or most cases.[35] In 2017, the state had an infant mortality rate of 6.2 deaths per 1,000 live births.[11] Number of reported abortions, abortion rate and percentage change in rate by geographic region and state in 1992, 1995 and 1996[36] Census division and state Number Rate % change 1992–1996 1992 1995 1996 1992 1995 1996 Total 1,528,930 1,363,690 1,365,730 25.9 22.9 22.9 –12 New England 78,360 71,940 71,280 25.2 23.6 23.5 –7 Connecticut 19,720 16,680 16,230 26.2 23 22.5 –14 Maine 4,200 2,690 2,700 14.7 9.6 9.7 –34 Massachusetts 40,660 41,190 41,160 28.4 29.2 29.3 3 New Hampshire 3,890 3,240 3,470 14.6 12 12.7 –13 Rhode Island 6,990 5,720 5,420 30 25.5 24.4 –19 Number of reported abortions and abortion rate, selected years; and percentage change in rate, 2008–2011—all by region and state in which the abortions occurred[37] Region and state Number Rate (abortions per 1,000 women aged 15–44.) % change 2008–2011 2008 2010 2011 2008 2010 2011 Total 1,212,350 1,102,670 1,058,490 19.4 17.7 16.9 −13 Northeast 302,710 281,250 272,020 27.1 25.3 24.6 −9 Connecticut 17,030 15,430 14,640 24.4 22.3 21.3 −13 Maine 2,800 2,490 2,360 11.2 10.3 9.9 −12 Massachusetts 24,900 24,360 24,030 18.4 18.0 17.8 −3 New Hampshire 3,200 3,040 3,200 12.4 12.2 12.9 4 New Jersey 54,160 48,840 46,990 30.9 28.1 27.1 −12 New York 153,110 142,790 138,370 37.7 35.3 34.2 −9 Pennsylvania 41,000 38,650 36,870 16.7 15.8 15.1 −9 Rhode Island 5,000 4,290 4,210 22.9 20.0 19.8 −13 Vermont 1,510 1,370 1,370 12.5 11.6 11.7 −7 Number of reported abortions and abortion rate in 2014, 2016 and 2017; and percentage change in rates between 2014 and 2017, all by region and state in which the abortion occurred[38] Region and state Number Rate (abortions per 1,000 women aged 15–44.) % change 2014–2017 2014 2016 2017 2014 2016 2017 U.S. Total 926,190 874,080 862,320 14.6 13.7 13.5 –8 Northeast 240,320 232,040 224,310 21.8 21.2 20.5 –6 Connecticut 13,140 12,210 11,910 19.2 18.1 17.7 –8 Maine 2,220 2,060 2,040 9.5 8.9 8.8 –7 Massachusetts 21,020 19,200 18,590 15.3 14.0 13.5 –12 New Hampshire 2,540 2,310 2,210 10.4 9.6 9.2 –12 New Jersey 44,460 48,300 48,110 25.8 28.2 28.0 9 New York 119,940 110,840 105,380 29.6 27.6 26.3 –11 Pennsylvania 32,030 32,230 31,260 13.3 13.5 13.1 –1 Rhode Island 3,580 3,510 3,500 17.0 16.8 16.7 –2 Vermont 1,400 1,360 1,300 12.1 12.0 11.4 –5 Number, rate, and ratio of reported abortions, by reporting area of residence and occurrence and by percentage of abortions obtained by out-of-state residents, US CDC estimates Location Residence Occurrence % obtained by out-of-state residents Year Ref No. Rate^ Ratio^^ No. Rate^ Ratio^^ Rhode Island 2,581 12.3 238 2,990 14.2 276 16 2014 [39] Rhode Island 2,348 11.2 214 2,649 12.6 241 14.7 2015 [40] Rhode Island 2,223 10.7 206 2,479 11.9 230 12.9 2016 [41] ^number of abortions per 1,000 women aged 15–44; ^^number of abortions per 1,000 live births ## Abortion rights views and activities[edit] ### Protests[edit] Women from the state participated in marches supporting abortion rights as part of a #StoptheBans movement in May 2019.[42] ## Footnotes[edit] 1. ^ According to the Supreme Court's decision in Roe v. Wade: > (a) For the stage prior to approximately the end of the first trimester, the abortion decision and its effectuation must be left to the medical judgement of the pregnant woman's attending physician. (b) For the stage subsequent to approximately the end of the first trimester, the State, in promoting its interest in the health of the mother, may, if it chooses, regulate the abortion procedure in ways that are reasonably related to maternal health. (c) For the stage subsequent to viability, the State in promoting its interest in the potentiality of human life may, if it chooses, regulate, and even proscribe, abortion except where it is necessary, in appropriate medical judgement, for the preservation of the life or health of the mother. Likewise, Black's Law Dictionary defines abortion as "knowing destruction" or "intentional expulsion or removal". ## References[edit] 1. ^ "Rhode Island codifies Roe v Wade into State Law". UpriseRI.com. 2. ^ "Campaign 2018 poll: Hot-button issues divide R.I. voters, lawmakers and Catholic church". Providence Journal. 3. ^ Watson, Katie (20 Dec 2019). "Why We Should Stop Using the Term "Elective Abortion"". AMA Journal of Ethics. 20: E1175-1180. doi:10.1001/amajethics.2018.1175. PMID 30585581. Retrieved 17 May 2019. 4. ^ Chamberlain, Pam; Hardisty, Jean (2007). "The Importance of the Political 'Framing' of Abortion". The Public Eye Magazine. 14 (1). 5. ^ "The Roberts Court Takes on Abortion". New York Times. November 5, 2006. Retrieved January 18, 2008. 6. ^ Brennan 'Dehumanizing the vulnerable' 2000 7. ^ Getek, Kathryn; Cunningham, Mark (February 1996). "A Sheep in Wolf's Clothing – Language and the Abortion Debate". Princeton Progressive Review. 8. ^ "Example of "anti-life" terminology" (PDF). Archived from the original (PDF) on 2011-07-27. Retrieved 2011-11-16. 9. ^ Goldstein, Norm, ed. The Associated Press Stylebook. Philadelphia: Basic Books, 2007. 10. ^ Castillo, Stephanie (2014-10-03). "States With More Abortion Restrictions Hurt Women's Health, Increase Risk For Maternal Death". Medical Daily. Retrieved 2019-05-27. 11. ^ a b c "States pushing abortion bans have highest infant mortality rates". NBC News. Retrieved May 25, 2019. 12. ^ a b Mundell, E.J. (January 16, 2019). "Two-Thirds of Poor U.S. Women Can't Afford Menstrual Pads, Tampons: Study". US News & World Report. Retrieved May 26, 2019. 13. ^ Larimer, Sarah (January 8, 2016). "The 'tampon tax,' explained". The Washington Post. Archived from the original on December 11, 2016. Retrieved December 10, 2016. 14. ^ Bowerman, Mary (July 25, 2016). "The 'tampon tax' and what it means for you". USA Today. Archived from the original on December 11, 2016. Retrieved December 10, 2016. 15. ^ Hillin, Taryn. "These are the U.S. states that tax women for having periods". Splinter. Retrieved 2017-12-15. 16. ^ "Election Results 2018: Nevada Ballot Questions 1-6". KNTV. Retrieved 2018-11-07. 17. ^ a b Buell, Samuel (1991-01-01). "Criminal Abortion Revisited". New York University Law Review. 66: 1774–1831. 18. ^ "State Policy On Informed Consent for Abortion" (PDF). Guttmacher Policy Review. Fall 2007. Retrieved May 22, 2019. 19. ^ "TRAP Laws Gain Political Traction While Abortion Clinics—and the Women They Serve—Pay the Price". Guttmacher Institute. 2013-06-27. Retrieved 2019-05-27. 20. ^ Lai, K. K. Rebecca (2019-05-15). "Abortion Bans: 8 States Have Passed Bills to Limit the Procedure This Year". The New York Times. ISSN 0362-4331. Retrieved 2019-05-24. 21. ^ a b c "Are there any states working to protect abortion rights?". Well+Good. 2019-05-17. Retrieved May 25, 2019. 22. ^ Tavernise, Sabrina (2019-05-15). "'The Time Is Now': States Are Rushing to Restrict Abortion, or to Protect It". The New York Times. ISSN 0362-4331. Retrieved 2019-05-24. 23. ^ "National Debate Over Abortion Laws Comes To Rhode Island". www.wbur.org. Retrieved 2019-05-23. 24. ^ Gregg, Katherine. "Abortion-rights bill voted down by R.I. Senate Judiciary Committee". providencejournal.com. Retrieved May 25, 2019. 25. ^ [1] 26. ^ [2] 27. ^ Alesha Doan (2007). Opposition and Intimidation: The Abortion Wars and Strategies of Political Harassment. University of Michigan Press. p. 57. ISBN 9780472069750. 28. ^ Casey, 505 U.S. at 877. 29. ^ a b Arndorfer, Elizabeth; Michael, Jodi; Moskowitz, Laura; Grant, Juli A.; Siebel, Liza (December 1998). A State-By-State Review of Abortion and Reproductive Rights. Diane Publishing. ISBN 9780788174810. 30. ^ Gould, Rebecca Harrington, Skye. "The number of abortion clinics in the US has plunged in the last decade — here's how many are in each state". Business Insider. Retrieved 2019-05-23. 31. ^ businessinsider (2018-08-04). "This is what could happen if Roe v. Wade fell". Business Insider (in Spanish). Retrieved 2019-05-24. 32. ^ "Here's Where Women Have Less Access to Planned Parenthood". Retrieved 2019-05-23. 33. ^ Cates, Willard; Rochat, Roger (March 1976). "Illegal Abortions in the United States: 1972–1974". Family Planning Perspectives. 8 (2): 86. doi:10.2307/2133995. JSTOR 2133995. PMID 1269687. 34. ^ "Guttmacher Data Center". data.guttmacher.org. Retrieved 2019-05-24. 35. ^ "Views about abortion by state - Religion in America: U.S. Religious Data, Demographics and Statistics \| Pew Research Center". Retrieved 2019-05-23. 36. ^ "Abortion Incidence and Services in the United States, 1995-1996". Guttmacher Institute. 2005-06-15. Retrieved 2019-06-02. 37. ^ "Abortion Incidence and Service Availability In the United States, 2011". Guttmacher Institute. 2014-02-14. Retrieved 2020-02-06. 38. ^ "Abortion Incidence and Service Availability in the United States, 2017". Guttmacher Institute. 2019-09-01. Retrieved 2020-02-06. 39. ^ Jatlaoui, Tara C. (2017). "Abortion Surveillance — United States, 2014". MMWR. Surveillance Summaries. 66 (24): 1–48. doi:10.15585/mmwr.ss6624a1. ISSN 1546-0738. PMID 29166366. 40. ^ Jatlaoui, Tara C. (2018). "Abortion Surveillance — United States, 2015". MMWR. Surveillance Summaries. 67 (13): 1–45. doi:10.15585/mmwr.ss6713a1. ISSN 1546-0738. PMC 6289084. PMID 30462632. 41. ^ Jatlaoui, Tara C. (2019). "Abortion Surveillance — United States, 2016". MMWR. Surveillance Summaries. 68. doi:10.15585/mmwr.ss6811a1. ISSN 1546-0738. 42. ^ Bacon, John. "Abortion rights supporters' voices thunder at #StopTheBans rallies across the nation". USA Today. Retrieved May 25, 2019. Abortion in the United States by state States * Alabama * Alaska * Arizona * Arkansas * California * Colorado * Connecticut * Delaware * Florida * Georgia * Hawaii * Idaho * Illinois * Indiana * Iowa * Kansas * Kentucky * Louisiana * Maine * Maryland * Massachusetts * Michigan * Minnesota * Mississippi * Missouri * Montana * Nebraska * Nevada * New Hampshire * New Jersey * New Mexico * New York * North Carolina * North Dakota * Ohio * Oklahoma * Oregon * Pennsylvania * Rhode Island * South Carolina * South Dakota * Tennessee * Texas * Utah * Vermont * Virginia * Washington * West Virginia * Wisconsin * Wyoming Federal district Washington, D.C. Insular areas * American Samoa * Guam * Northern Mariana Islands * Puerto Rico * U.S. Virgin Islands [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Abortion in Rhode Island	None	29,134	wikipedia	https://en.wikipedia.org/wiki/Abortion_in_Rhode_Island	2021-01-18T18:56:15	{"wikidata": ["Q64876952"]}
Group of autoimmune diseases resulting in abnormal growth of connective tissue This article is about the disease. For the mushroom, see Scleroderma (fungus). Not to be confused with scleredema. Scleroderma A type of localized scleroderma known as morphea SpecialtyRheumatology Usual onsetMiddle age[1] TypesLocalized, systemic scleroderma[2] CausesUnknown[2] Risk factorsFamily history, certain genetic factors, exposure to silica[3][4][5] Diagnostic methodBased on symptoms, skin biopsy, blood tests[6] Differential diagnosisMixed connective tissue disease, systemic lupus erythematosus, polymyositis, dermatomyositis[1] TreatmentSupportive care[1] MedicationCorticosteroids, methotrexate, non-steroidal anti-inflammatory drugs (NSAIDs)[2] PrognosisLocalized: Normal life expectancy[7] Systemic: Decreased life expectancy[3] Frequency3 per 100,000 per year (systemic)[3] Scleroderma is a group of autoimmune diseases that may result in changes to the skin, blood vessels, muscles, and internal organs.[2][6] The disease can be either localized to the skin or involve other organs as well.[2] Symptoms may include areas of thickened skin, stiffness, feeling tired, and poor blood flow to the fingers or toes with cold exposure.[1] One form of the condition, known as CREST syndrome, classically results in calcium deposits, Raynaud's syndrome, esophageal problems, thickening of the skin of the fingers and toes, and areas of small dilated blood vessels.[1] The cause is unknown; however, some suspect it may be due to an abnormal immune response.[2] Risk factors include family history, certain genetic factors, and exposure to silica.[3][4][5] The underlying mechanism involves the abnormal growth of connective tissue which is believed to be the result of the immune system attacking healthy tissues.[6] Diagnosis is based on symptoms, supported by a skin biopsy or blood tests.[6] While there is no cure, treatment may improve symptoms.[2] Medications used include corticosteroids, methotrexate, and non-steroidal anti-inflammatory drugs (NSAIDs).[2] Outcome depends on the extent of disease.[3] Those with localized disease generally have a normal life expectancy.[7] In those with systemic disease typical life expectancy is about 11 years from onset.[3] Death is often due to lung, gastrointestinal, or heart complications.[3] About 3 out of 100,000 people per year develop the systemic form.[3] The condition most often begins in middle age.[1] Women are more often affected than men.[1] Scleroderma symptoms were first described in 1753 by Carlo Curzio[8] and then well documented in 1842.[9] The term is from the Greek skleros meaning "hard" and derma meaning "skin".[10] ## Contents * 1 Signs and symptoms * 2 Cause * 3 Pathophysiology * 4 Diagnosis * 4.1 Differential * 4.2 Classification * 5 Treatment * 6 Prognosis * 7 Epidemiology * 8 Pregnancy * 9 See also * 10 References * 11 External links ## Signs and symptoms[edit] Arm of a person with scleroderma showing skin lesions Dark, shiny skin on distal phalanges of both hands in systemic sclerosis Potential signs and symptoms include:[11][12][13] * Cardiovascular: Raynaud's phenomenon (is the presenting symptom in 30% of affected persons, occurs in 95% of affected individuals at some time during their illness); healed pitting ulcers on the fingertips; skin and mucosal telangiectasis; palpitations, irregular heart rate and fainting due to conduction abnormalities, hypertension and congestive heart failure. * Digestive: gastroesophageal reflux disease, bloating, indigestion, loss of appetite, diarrhoea alternating with constipation, sicca syndrome and its complications, loosening of teeth and hoarseness (due to acid reflux). * Pulmonary: progressive worsening of shortness of breath, chest pain (due to pulmonary artery hypertension) and dry, persistent cough due to interstitial lung disease. * Musculoskeletal: joint, muscle aches, loss of joint range of motion, carpal tunnel syndrome and muscle weakness. * Genitourinary: erectile dysfunction, dyspareunia, kidney problems, or kidney failure. * Other: facial pain due to trigeminal neuralgia, hand paresthesias, headache, stroke, fatigue, calcinosis and weight loss. ## Cause[edit] Scleroderma is caused by genetic and environmental factors.[4][5][14][15] Mutations in HLA genes seem to play a crucial role in the pathogenesis of some cases (but not all), likewise silica, aromatic and chlorinated solvents, ketones, trichloroethylene, welding fumes and white spirits exposure seems to contribute to the condition in a small proportion of affected persons.[4][5][14][15][16] ## Pathophysiology[edit] It is characterised by increased synthesis of collagen (leading to the sclerosis), damage to small blood vessels, activation of T lymphocytes and production of altered connective tissues.[17] Its proposed pathogenesis is the following:[18][19][20][21][22] * It begins with an inciting event at the level of the vasculature, probably the endothelium. The inciting event is yet to be elucidated but may be a viral agent, oxidative stress or autoimmune. Endothelial cell damage and apoptosis ensue, leading to the vascular leakiness that manifests in early clinical stages as tissue oedema. At this stage it is predominantly a Th1 and Th17-mediated disease. * After this the vasculature is further compromised by impaired angiogenesis and impaired vasculogenesis (fewer endothelial progenitor cells), likely related to the presence of antiendothelinal cell antibodies (AECA). Despite this impaired angiogenesis, elevated levels of pro-angiogenic growth factors like PDGF and VEGF is often seen in persons with the condition. The balance of vasodilation and vasoconstriction becomes off-balance and the net result is vasoconstriction. The damaged endothelium then serves as a point of origin for blood clot formation and further contributes to ischaemia-reperfusion injury and the generation of reactive oxygen species. These later stages are characterised by Th2 polarity. * The damaged endothelium upregulates adhesion molecules and chemokines to attract leucocytes, which enables the development of innate and adaptive immune responses, including loss of tolerance to various oxidised antigens, which includes topoisomerase I. B cells mature into plasma cells, which furthers the autoimmune component of the condition. T cells differentiate into subsets, including Th2 cells, which play a vital role in tissue fibrosis. Anti–topoisomerase 1 antibodies, in turn, stimulate type I interferon production. * Fibroblasts are recruited and activated by multiple cytokines and growth factors to generate myofibroblasts. Dysregulated transforming growth factor β (TGF-β) signalling in fibroblasts and myofibroblasts has been observed in multiple studies of scleroderma-affected individuals. Activation of fibroblasts and myofibroblasts leads to excessive deposition of collagen and other related proteins, leading to fibrosis. B cells are implicated in this stage, IL-6 and TGF-β produced by the B cells decrease collagen degradation and increase extracellular matrix production. Endothelin signalling is implicated in the pathophysiology of fibrosis.[23] Vitamin D is implicated in the pathophysiology of the disease. An inverse correlation between plasma levels of vitamin D and scleroderma severity has been noted and vitamin D is known to play a crucial role in regulating (usually suppressing) the actions of the immune system.[24] ## Diagnosis[edit] Typical scleroderma is classically defined as symmetrical skin thickening, with about 70% of cases also presenting with Raynaud's phenomenon, nail-fold capillary changes and antinuclear antibodies. Affected individuals may or may not experience systemic organ involvement. There is no single test for scleroderma that works all of the time and hence the diagnosis is often a matter of exclusion. Atypical scleroderma may show any variation of these changes without skin changes or with finger swelling only.[25] Laboratory testing can show antitopoisomerase antibodies, like anti-scl70 (causing a diffuse systemic form), or anticentromere antibodies (causing a limited systemic form and the CREST syndrome). Other autoantibodies can be seen, such as anti-U3 or anti-RNA polymerase.[26] Anti-double-stranded DNA (ds DNA) autoantibodies likely to be present in serum.[citation needed] ### Differential[edit] Diseases that are often in the differential include:[27] * Eosinophilia, a condition in which there are too many eosinophils (a type of immune cell that attacks parasites and is involved in certain allergic reactions) in the blood. * Eosinophilia-myalgia syndrome, a form of eosinophilia that is caused by L-tryptophan supplements. * Eosinophilic fasciitis, a disease that affects the connective tissues surrounding skeletal muscles, bones, blood vessels and nerves in the arms and legs. * Graft-versus-host disease, an autoimmune condition that occurs as a result of bone marrow transplants in which the immune cells from the transplanted bone marrow attack the host's body. * Mycosis fungoides, a type of cutaneous T cell lymphoma, a rare cancer that causes rashes all over the body. * Nephrogenic systemic fibrosis, a condition usually caused by kidney failure that causes fibrosis (thickening) of the tissues. * Primary biliary cirrhosis, an autoimmune disease of the liver. * Primary pulmonary hypertension * Complex regional pain syndrome ### Classification[edit] Scleroderma is characterised by the appearance of circumscribed or diffuse, hard, smooth, ivory-colored areas that are immobile and which give the appearance of hidebound skin, a disease occurring in both localised and systemic forms:[28] * Localised scleroderma * Localised morphea * Morphea-lichen sclerosus et atrophicus overlap * Generalised morphea * Atrophoderma of Pasini and Pierini * Pansclerotic morphea * Morphea profunda * Linear scleroderma * Systemic scleroderma * CREST syndrome * Progressive systemic sclerosis ## Treatment[edit] There is no cure for scleroderma, although relief of symptoms is often achieved. These include the following:[11][29] * Raynaud's phenomenon with vasodilators such as calcium channel blockers, alpha blockers, serotonin receptor antagonists, angiotensin II receptor inhibitors, statins, local nitrates or iloprost * Digital ulcers with phosphodiesterase 5 inhibitors (e.g., sildenafil) or iloprost * Prevention of new digital ulcers with bosentan * Malnutrition, secondary to intestinal flora overgrowth with tetracycline antibiotics like tetracycline * Interstitial lung disease with cyclophosphamide, azathioprine with or without corticosteroids * Pulmonary arterial hypertension with endothelin receptor antagonists, phosphodiesterase 5 inhibitors and prostanoids * Gastrooesophageal reflux disease with antacids or prokinetics * Kidney crises with angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists Systemic disease-modifying treatment with immunosuppressants is often used.[14][30][31][32][33][34] Immunosuppressants used in its treatment include azathioprine, methotrexate, cyclophosphamide, mycophenolate, intravenous immunoglobulin, rituximab, sirolimus, alefacept and the tyrosine kinase inhibitors, imatinib, nilotinib and dasatinib.[14][29][30][31][32][33][34][35] Experimental therapies under investigation include endothelin receptor antagonists, tyrosine kinase inhibitors, beta-glycan peptides, halofuginone, basiliximab, alemtuzumab, abatacept and haematopoietic stem cell transplantation.[36][37] Immunomodulatory agents in the treatment of scleroderma INN Mechanism of action[38][39] Route of administration[38] Pregnancy category[38][40] Major toxicities[38] Alefacept Monoclonal antibody to inhibit T lymphocyte activation by binding to CD2 portion of human leukocyte function antigen-3. IM B (US) Malignancies, injection site reactions, blood clots, lymphopenia, hepatotoxicity and infections. Azathioprine Purine analogue that inhibits lymphocyte proliferation via conversion to mercaptopurine PO, IV D (Au) Myelosuppression and rarely malignancy, hepatitis, infection, hepatic sinusoidal obstruction syndrome and hypersensitivity reactions. Cyclophosphamide Nitrogen mustard that cross-links DNA base pairs, leading to breakages and triggering apoptosis in haematopoietic cells. PO, IV D (Au) Vomiting, myelosuppression, haemorrhagic cystitis and rarely heart failure, pulmonary fibrosis, hepatic sinusoidal obstruction syndrome, malignancy and SIADH. Dasatinib Tyrosine kinase inhibitor against various pro-angiogenic growth factors (including PDGF and VEGF). PO D (Au) Fluid retention, myelosuppression, haemorrhage, infections, pulmonary hypertension, electrolyte anomalies and uncommonly hepatotoxicity, heart dysfunction/failure, myocardial infarction, QT interval prolongation, renal failure and hypersensitivity. Imatinib As above. PO D (Au) As above and rarely: GI perforation, avascaular necrosis and rhabdomyolysis. Immunoglobulin Immunoglobulin, modulates the immune system. IV N/A Varies. Methotrexate Antifolate; inhibits dihydrofolate reductase. PO, IV, IM, SC, IT D (Au) Myeosuppression, pulmonary toxicity, hepatotoxicity, neurotoxicity and rarely kidney failure, hypersensitivity reactions, skin and bone necrosis and osteoporosis. Mycophenolate Inosine monophosphate dehydrogenase inhibitor, leading to reduced purine biosynthesis in lymphocytes. PO, IV D (Au) Myelosuppression, blood clots, less commonly GI perforation/haemorrhage and rarely pancreatitis, hepatitis, aplastic anaemia and pure red cell aplasia. Nilotinib As per dasatinib. PO D (Au) As per imatinib. Rituximab Monoclonal antibody against CD20 which is expressed on B lymphocytes. IV C (Au) Infusion-related reactions, infection, neutropenia, reduced immunoglobulin levels, arrhythmias, less commonly anaemia, thrombocytopenia, angina, myocardial infarction, heart failure and rarely haemolytic anaemia, aplastic anaemia, serum sickness, severe skin conditions, pulmonary infiltrates, pneumonitis, cranial neuropathy (vision or hearing loss) and progressive multifocal leucoencephalopathy. Sirolimus mTOR inhibitor, thereby reducing cytokine-induced lymphocyte proliferation. PO C (Au) Neutropenia, hypokalaemia, interstitial lung disease, pericardial effusion, pleural effusion, less commonly pulmonary haemorrhage, nephrotic syndrome and rarely hepatotoxicity and lymphoedema. PO = Oral. IV = Intravenous. IM = Intramuscular. SC = Subcutaneous. IT = Intrathecal. The preferred pregnancy category, above, is Australian, if available. If unavailable an American one is substituted. ## Prognosis[edit] The five-year survival rate for systemic scleroderma is about 85%, whereas the 10-year survival rate is just under 70%.[41] This varies according to the subtype; while localized scleroderma rarely results in death, the systemic form can, and the diffuse systemic form carries a worse prognosis than the limited form. The major scleroderma-related causes of death are: pulmonary hypertension, pulmonary fibrosis, and scleroderma renal crisis.[26] People with scleroderma are also at a heightened risk for contracting cancers (especially liver, lung, haematologic and bladder cancers) and, perhaps, cardiovascular disease.[42][43][44][45][46][47][excessive citations] According to a study of an Australian cohort, between 1985 and 2015, the average life expectancy of a person with scleroderma increased from 66 years to 74 years (around 8 years less than the average Australian life expectancy of 82 years).[48] ## Epidemiology[edit] Scleroderma most commonly first presents between the ages of 20 and 50 years, although any age group can be affected.[11][26] Women are four to nine times more likely to develop scleroderma than men.[26] This disease is found worldwide.[26] In the United States, prevalence is estimated at 240 per million and the annual incidence of scleroderma is 19 per million people.[26] Likewise in the United States, it is slightly more common in African Americans than in their white counterparts. Choctaw Native Americans are more likely than Americans of European descent to develop the type of scleroderma that affects internal organs.[26] In Germany, the prevalence is between 10 and 150 per million people, and the annual incidence is between 3 and 28 per million people.[41] In South Australia, the annual incidence is 23 per million people, and the prevalence 233 per million people.[49] Scleroderma is less common in the Asian population.[50] ## Pregnancy[edit] Scleroderma in pregnancy is a complex situation; it increases the risk to both mother and child.[51] Overall scleroderma is associated with reduced fetal weight for gestational age.[51] The treatment for scleroderma often includes known teratogens such as cyclophosphamide, methotrexate, mycophenolate, etc. and hence careful avoidance of such drugs during pregnancy is advised.[51] In these cases hydroxychloroquine and low-dose corticosteroids might be used for disease control.[51] ## See also[edit] * Congenital fascial dystrophy ## References[edit] 1. ^ a b c d e f g "Scleroderma". 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PMID 22155199. ## External links[edit] * Handout on Health: Scleroderma—US National Institute of Arthritis and Musculoskeletal and Skin Diseases Classification D * ICD-10: L94.0–L94.1, M34 * ICD-9-CM: 701.0 710.1 * SNOMED CT: 201441006 External resources * MedlinePlus: 000429 * Orphanet: 801 * v * t * e Diseases of the skin and appendages by morphology Growths Epidermal * Wart * Callus * Seborrheic keratosis * Acrochordon * Molluscum contagiosum * Actinic keratosis * Squamous-cell carcinoma * Basal-cell carcinoma * Merkel-cell carcinoma * Nevus sebaceous * Trichoepithelioma Pigmented * Freckles * Lentigo * Melasma * Nevus * Melanoma Dermal and subcutaneous * Epidermal inclusion cyst * Hemangioma * Dermatofibroma (benign fibrous histiocytoma) * Keloid * Lipoma * Neurofibroma * Xanthoma * Kaposi's sarcoma * Infantile digital fibromatosis * Granular cell tumor * Leiomyoma * Lymphangioma circumscriptum * Myxoid cyst Rashes With epidermal involvement Eczematous * Contact dermatitis * Atopic dermatitis * Seborrheic dermatitis * Stasis dermatitis * Lichen simplex chronicus * Darier's disease * Glucagonoma syndrome * Langerhans cell histiocytosis * Lichen sclerosus * Pemphigus foliaceus * Wiskott–Aldrich syndrome * Zinc deficiency Scaling * Psoriasis * Tinea (Corporis * Cruris * Pedis * Manuum * Faciei) * Pityriasis rosea * Secondary syphilis * Mycosis fungoides * Systemic lupus erythematosus * Pityriasis rubra pilaris * Parapsoriasis * Ichthyosis Blistering * Herpes simplex * Herpes zoster * Varicella * Bullous impetigo * Acute contact dermatitis * Pemphigus vulgaris * Bullous pemphigoid * Dermatitis herpetiformis * Porphyria cutanea tarda * Epidermolysis bullosa simplex Papular * Scabies * Insect bite reactions * Lichen planus * Miliaria * Keratosis pilaris * Lichen spinulosus * Transient acantholytic dermatosis * Lichen nitidus * Pityriasis lichenoides et varioliformis acuta Pustular * Acne vulgaris * Acne rosacea * Folliculitis * Impetigo * Candidiasis * Gonococcemia * Dermatophyte * Coccidioidomycosis * Subcorneal pustular dermatosis Hypopigmented * Tinea versicolor * Vitiligo * Pityriasis alba * Postinflammatory hyperpigmentation * Tuberous sclerosis * Idiopathic guttate hypomelanosis * Leprosy * Hypopigmented mycosis fungoides Without epidermal involvement Red Blanchable Erythema Generalized * Drug eruptions * Viral exanthems * Toxic erythema * Systemic lupus erythematosus Localized * Cellulitis * Abscess * Boil * Erythema nodosum * Carcinoid syndrome * Fixed drug eruption Specialized * Urticaria * Erythema (Multiforme * Migrans * Gyratum repens * Annulare centrifugum * Ab igne) Nonblanchable Purpura Macular * Thrombocytopenic purpura * Actinic/solar purpura Papular * Disseminated intravascular coagulation * Vasculitis Indurated * Scleroderma/morphea * Granuloma annulare * Lichen sclerosis et atrophicus * Necrobiosis lipoidica Miscellaneous disorders Ulcers * Hair * Telogen effluvium * Androgenic alopecia * Alopecia areata * Systemic lupus erythematosus * Tinea capitis * Loose anagen syndrome * Lichen planopilaris * Folliculitis decalvans * Acne keloidalis nuchae Nail * Onychomycosis * Psoriasis * Paronychia * Ingrown nail Mucous membrane * Aphthous stomatitis * Oral candidiasis * Lichen planus * Leukoplakia * Pemphigus vulgaris * Mucous membrane pemphigoid * Cicatricial pemphigoid * Herpesvirus * Coxsackievirus * Syphilis * Systemic histoplasmosis * Squamous-cell carcinoma * v * t * e Cutaneous keratosis, ulcer, atrophy, and necrobiosis Epidermal thickening * keratoderma: Keratoderma climactericum * Paraneoplastic keratoderma * Acrokeratosis paraneoplastica of Bazex * Aquagenic keratoderma * Drug-induced keratoderma * psoriasis * Keratoderma blennorrhagicum * keratosis: Seborrheic keratosis * Clonal seborrheic keratosis * Common seborrheic keratosis * Irritated seborrheic keratosis * Seborrheic keratosis with squamous atypia * Reticulated seborrheic keratosis * Dermatosis papulosa nigra * Keratosis punctata of the palmar creases * other hyperkeratosis: Acanthosis nigricans * Confluent and reticulated papillomatosis * Callus * Ichthyosis acquisita * Arsenical keratosis * Chronic scar keratosis * Hyperkeratosis lenticularis perstans * Hydrocarbon keratosis * Hyperkeratosis of the nipple and areola * Inverted follicular keratosis * Lichenoid keratosis * Multiple minute digitate hyperkeratosis * PUVA keratosis * Reactional keratosis * Stucco keratosis * Thermal keratosis * Viral keratosis * Warty dyskeratoma * Waxy keratosis of childhood * other hypertrophy: Keloid * Hypertrophic scar * Cutis verticis gyrata Necrobiosis/granuloma Necrobiotic/palisading * Granuloma annulare * Perforating * Generalized * Subcutaneous * Granuloma annulare in HIV disease * Localized granuloma annulare * Patch-type granuloma annulare * Necrobiosis lipoidica * Annular elastolytic giant-cell granuloma * Granuloma multiforme * Necrobiotic xanthogranuloma * Palisaded neutrophilic and granulomatous dermatitis * Rheumatoid nodulosis * Interstitial granulomatous dermatitis/Interstitial granulomatous drug reaction Foreign body granuloma * Beryllium granuloma * Mercury granuloma * Silica granuloma * Silicone granuloma * Zirconium granuloma * Soot tattoo * Tattoo * Carbon stain Other/ungrouped * eosinophilic dermatosis * Granuloma faciale Dermis/ localized CTD Cutaneous lupus erythematosus * chronic: Discoid * Panniculitis * subacute: Neonatal * ungrouped: Chilblain * Lupus erythematosus–lichen planus overlap syndrome * Tumid * Verrucous * Rowell's syndrome Scleroderma/ Morphea * Localized scleroderma * Localized morphea * Morphea–lichen sclerosus et atrophicus overlap * Generalized morphea * Atrophoderma of Pasini and Pierini * Pansclerotic morphea * Morphea profunda * Linear scleroderma Atrophic/ atrophoderma * Lichen sclerosus * Anetoderma * Schweninger–Buzzi anetoderma * Jadassohn–Pellizzari anetoderma * Atrophoderma of Pasini and Pierini * Acrodermatitis chronica atrophicans * Semicircular lipoatrophy * Follicular atrophoderma * Linear atrophoderma of Moulin Perforating * Kyrle disease * Reactive perforating collagenosis * Elastosis perforans serpiginosa * Perforating folliculitis * Acquired perforating dermatosis Skin ulcer * Pyoderma gangrenosum Other * Calcinosis cutis * Sclerodactyly * Poikiloderma vasculare atrophicans * Ainhum/Pseudo-ainhum * v * t * e Systemic connective tissue disorders General Systemic lupus erythematosus * Drug-induced SLE * Libman–Sacks endocarditis Inflammatory myopathy * Myositis * Dermatopolymyositis * Dermatomyositis/Juvenile dermatomyositis * Polymyositis* Inclusion body myositis Scleroderma * Systemic scleroderma * Progressive systemic sclerosis * CREST syndrome * Overlap syndrome / Mixed connective tissue disease Other hypersensitivity/autoimmune * Sjögren syndrome Other * Behçet's disease * Polymyalgia rheumatica * Eosinophilic fasciitis * Eosinophilia–myalgia syndrome * fibrillin * Marfan syndrome * Congenital contractural arachnodactyly Authority control * NDL: 00567132 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Scleroderma	c0011644	29,135	wikipedia	https://en.wikipedia.org/wiki/Scleroderma	2021-01-18T18:43:06	{"gard": ["10308"], "mesh": ["D012594"], "umls": ["C0011644"], "icd-9": ["710.1", "701.0"], "icd-10": ["L94.0", "L94.1", "M34"], "orphanet": ["801"], "wikidata": ["Q958797"]}
Hypotrichosis simplex (HS) or hereditary hypotrichosis simplex (HHS) is characterized by reduced pilosity over the scalp and body (with sparse, thin, and short hair) in the absence of other anomalies. ## Epidemiology Prevalence is unknown but numerous large pedigrees with several affected members have been described. Both men and women are equally affected. ## Clinical description Hair loss is diffuse and progressive and usually begins during early childhood. Body hair may also be sparse with variable involvement of the eyebrows, eyelashes, and pubic and axillary hair. There are no anomalies of the skin, nails or teeth. A scalp-limited form, hypotrichosis simplex of the scalp (see this term) has also been reported with mutations in the corneodesmosin (CDSN) gene. ## Etiology Both autosomal dominant and recessive modes of transmission have been reported for HHS.Autosomal dominant HHS affecting both scalp and body hair has been reported in one Italian and two Pakistani families as due to mutations in the APCDD1 gene mapped to 18p11.22. Three clinically similar forms of localized autosomal recessive hypotrichosis (LAH1, LAH2 and LAH3) have been identified within the last years. The locus for LAH1 (involving mainly the hair of the scalp, chest, arms and legs) has been mapped to 18q12.1 and mutations in the desmoglein-4 (DSG4) gene have been identified. The locus for LAH2 (characterized by sparse or absent scalp, axillary and body hair, and sparse eyebrows and eyelashes) has been mapped to 3q27.3 and mutations in the lipase-H (LIPH) gene have been identified. The locus for LAH3 (characterized by progressive loss of scalp hair, sparse body hair, and normal eyebrows, eyelashes, and pubic and axillary hair) has been mapped to 13q14.11-q21.32 and mutations have been identified in a G protein-coupled receptor gene (P2RY5). These receptors belong to the group of lipophosphatidic acid (LPA) receptors and are therefore designated as LPAR6. ## Management and treatment There is no treatment for hypotrichosis simplex available to date. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Hypotrichosis simplex	c1854310	29,136	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=55654	2021-01-23T17:57:44	{"gard": ["9170"], "mesh": ["C537160"], "omim": ["278150", "604379", "605389", "607903", "614237", "614238", "615059", "615885", "618275"], "umls": ["C1854310"], "icd-10": ["L65.8"], "synonyms": ["Hereditary hypotrichosis simplex"]}
## Description The Richieri-Costa/Guion-Almeida syndrome is characterized by mild mental retardation, short stature, microbrachycephaly, ptosis, esotropia, cleft lip/palate (Richieri-Costa and Guion-Almeida, 1992). Clinical Features Richieri-Costa and Guion-Almeida (1992) described 3 Brazilian brothers with short stature, microbrachycephaly, mental retardation, prominent supraorbital ridges, asymmetric palpebral fissures, palpebral ptosis, deep-set eyes, coloboma of iris and retina, nystagmus, strabismus, malar hypoplasia, and cleft lip/palate. Richieri-Costa et al. (1992) described 2 Brazilian sisters with a combination of clinical signs interpreted as representing a 'new' autosomal recessive multiple congenital anomalies/mental retardation (MCA/MR) syndrome. Features included short stature, mental retardation, microbrachycephaly, temporal narrowness, thin/long face, hypotelorism, palpebral ptosis, strabismus, abnormal ears, marked hypoplasia of the midface, cleft lip, obtuse angle of the mandible, large and prominent chin, pectus excavatum, minor acral anomalies, wrinkled skin of hands and feet, lymphedema, abnormally modeled lumbosacral and pelvic bones, and lumbar lordosis. Natacci et al. (1999) described a boy with short stature, mental retardation, microbrachycephaly, palpebral ptosis, asymmetric and downslanted palpebral fissures, deep-set eyes, strabismus, coloboma of the iris, malar hypoplasia, cleft lip/palate, prominent mandible, and deafness. Natacci et al. (1999) suggested that this phenotype was the same as that described by Richieri-Costa and Guion-Almeida (1992) in 3 Brazilian brothers. Nystagmus and retinal coloboma were the only minor signs shared by the Brazilian brothers but not observed in this boy, and the boy had deafness, which was not reported in the brothers. Castori et al. (2011) described a 17-year-old man with mental retardation, microcephaly, prominent supraorbital ridges, deep-set eyes, ptosis, esotropia, asymmetric palpebral fissures, nystagmus, cleft eyelid, malar hypoplasia, cleft lip/palate, and spina bifida occulta. Audiometric exam, standard peripheral karyotype, 22q11.2 rearrangement investigation, and a 200-kb CGH array were all normal. Brain MRI was unremarkable with normal anterior-posterior diameter on both eyes. Castori et al. (2011) suggested classifying the patients described by Richieri-Costa and Guion-Almeida (1992) and Natacci et al. (1999) as Richieri-Costa/Guion-Almeida syndrome type 1 (RCGAS1) and the patients described by Richieri-Costa et al. (1992) as Richieri-Costa/Guion-Almeida syndrome type 2 (RCGAS2). Castori et al. (2011) noted that mental retardation, short stature, microbrachycephaly, ptosis, and esotropia are present in both RCGAS1 and RCGAS2, but suggested that the overall facial dysmorphism in each is distinct. In RCGAS1, eyelid ptosis is strikingly asymmetrical and is combined with prominent supraorbital ridges/deep-set eyes and a highly penetrant cleft lip/palate. RCGAS2 shows more severe shortness of the anterior-posterior diameter of the cranial vault as well as hypoplastic supraorbital ridges, a long, thin face, pointed chin, and obtuse mandibular angle; in addition, ptosis is symmetrical, cleft lip is not consistent feature, the palate is normal, and there are mild anomalies of the limbs and axial skeleton. Castori et al. (2011) also noted that their patient had features of both RCGAS1 and RCGAS2, but most closely resembled RCGAS1, and had some different features such as spina bifida occulta and absence of short stature. Castori et al. (2011) stated that it was unclear whether the phenotypes they discussed in their report represent separate entities or variability of a single entity. Inheritance Richieri-Costa and Guion-Almeida (1992) described 3 Brazilian brothers with short stature, mental retardation, eye anomalies, and cleft lip/palate. The parents were not affected. The authors suggested either autosomal recessive or X-linked recessive inheritance of the disorder. Richieri-Costa et al. (1992) suggested autosomal recessive inheritance of an MCA/MR syndrome in 2 Brazilian sisters whose parents were unaffected. INHERITANCE \- ?Autosomal recessive HEAD & NECK Face \- Malar hypoplasia Ears \- Deafness Eyes \- Prominent supraorbital ridges \- Asymmetric palpebral fissure \- Deep-set eyes \- Nystagmus \- Coloboma of the iris \- Coloboma of the retina \- Downslanting palpebral fissures \- Hypoplastic supraorbital ridges \- Esotropia \- Cleft eyelid Mouth \- Cleft palate \- Prominent mandible SKELETAL Spine \- Lumbosacral anomalies \- Spina bifida occulta Pelvis \- Pelvic anomalies Hands \- Digital anomalies Feet \- Digital anomalies SKIN, NAILS, & HAIR Skin \- Wrinkling of skin on limbs NEUROLOGIC Central Nervous System \- Hypotonia \- Ataxic gait Behavioral Psychiatric Manifestations \- Autism MISCELLANEOUS \- Possibly X-linked recessive inheritance ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	RICHIERI-COSTA/GUION-ALMEIDA SYNDROME	c0796142	29,137	omim	https://www.omim.org/entry/268850	2019-09-22T16:22:30	{"mesh": ["C563119"], "omim": ["268850"], "orphanet": ["2511"], "synonyms": ["Alternative titles", "Richieri Costa-Guion Almeida-Ramos syndrome", "SHORT STATURE, MENTAL RETARDATION, EYE ANOMALIES, AND CLEFT LIP/PALATE", "SAO PAULO MCA/MR SYNDROME"]}
## Description Total anomalous pulmonary venous return (TAPVR) is a cyanotic form of congenital heart defect in which the pulmonary veins fail to enter the left atrium and instead drain into the right atrium or one of the venous tributaries (summary by Bleyl et al., 1994). Clinical Features Neill et al. (1960) described father and daughter with hypoplastic right lung with systemic arterial supply and venous drainage. They referred to the disorder as the 'scimitar syndrome' because of the radiographic appearance created by the anomalous vein draining the right lower lung and connecting with the inferior vena cava. The father was asymptomatic but had been rejected for military service because his heart was said to be on the right side. The daughter had severe pulmonary hypertension, frequent respiratory infections, and marked hypoplasia of the right lung with dextroposition of the heart. Vinh et al. (1968) described a brother and sister, offspring of nonconsanguineous parents, with total infradiaphragmatic pulmonary venous return. In 2 brothers and a male paternal first cousin, Paz and Castilla (1971) observed total anomalous pulmonary venous return. Kaufman et al. (1972) described total anomalous pulmonary venous return of the figure-of-eight type in 2 sisters and a daughter of their maternal uncle. Chelius et al. (1962) described partial anomalous pulmonary venous return in 2 brothers whose maternal grandmother died at age 42 of congenital heart disease. Solymar et al. (1987) reported 3 pairs of sibs with total anomalous pulmonary venous connection. Four of the affected persons were male. Even in the same family, the connection was supracardial in one and infracardial in the other, indicating that genetic regulation deals with the left atrial connection to the intrapulmonary veins. Having failed to establish this connection, the intrapulmonary veins attach themselves to any adjacent venous structure; hence, the variety of connections found at birth. Raisher et al. (1991) reported total anomalous pulmonary venous connections in a father and his son and daughter. There was no known consanguinity in the family. Bleyl et al. (1993) and Bleyl et al. (1994) reported a large Utah-Idaho family of Scottish origin in which nonsyndromic TAPVR appeared to be inherited as an autosomal dominant with incomplete penetrance and variable expression. The family contained 14 affected individuals. Mapping By linkage mapping with polymorphic microsatellite markers in a large Utah-Idaho family of Scottish origin segregating TAPVR, Bleyl et al. (1994, 1995) localized the TAPVR1 locus to a 30-cM interval on 4p13-q12; maximum lod = 6.51 at theta = 0.0. A vascular epithelial growth factor receptor, thought to have a role in vasculogenesis, also mapped near the centromere and therefore was considered a candidate for the TAPVR gene. Kinase insert domain receptor (KDR; 191306) and its mouse homolog, fetal liver kinase-1, bind vascular endothelial growth factor with high affinity in vitro and are expressed early in development by endothelial cell precursors. The mouse homolog has been implicated in the development of blood and blood vessels. KDR maps to 4q12. Ward (1996) observed 10 families with multiple cases of TAPVR in Utah; 4 families failed to show linkage to 4q12-q13. The original family and others that derived from Scotland had the same haplotype. The region of mapping was one in which very low recombination occurs. Bleyl et al. (2006) identified a second Utah family of Scottish origin in which 2 members had TAPVR. Extensive genealogic analysis could not identify a common ancestor with the first large Utah family of Scottish origin reported by Bleyl et al. (1994). However, haplotype analysis demonstrated identity by descent in these 2 families, suggesting a remote Scottish founder. Haplotype analysis and recombination events refined the TAPVR1 locus to a 4.16-cM (2.48-Mb) region on chromosome 4q12 between D4S1630 and D4S3019. The haplotype was not identified in 238 control chromosomes. Penetrance of the anomaly was estimated to be 40%. Population Genetics Bleyl et al. (2010) stated that TAPVR affects 1 in 15,000 live births. Animal Model In gene expression studies in mouse and chick embryos for both the Pdgfra receptor (PDGFRA; 173490) and its ligand, Pdgfa, Bleyl et al. (2010) showed temporal and spatial patterns consistent with a role in pulmonary vein development. Loss of PDGFRA function in both chick and mouse embryos caused TAPVR with low penetrance (approximately 7%), reminiscent of that observed in human TAPVR kindreds. Intermediate inflow tract anomalies occurred in a higher percentage of embryos (approximately 30%), suggesting that TAPVR may occur at one end of a spectrum of defects. INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Cardiac dextroposition Vascular \- Scimitar appearance of anomalous right lower pulmonary vein Pulmonary hypertension RESPIRATORY Lung \- Hypoplastic right lung \- Frequent respiratory infections ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	TOTAL ANOMALOUS PULMONARY VENOUS RETURN 1	c4551904	29,138	omim	https://www.omim.org/entry/106700	2019-09-22T16:44:59	{"doid": ["4297"], "mesh": ["D012587"], "omim": ["106700"], "icd-10": ["Q26.2"], "orphanet": ["99125"], "synonyms": ["Alternative titles", "SCIMITAR ANOMALY", "ANOMALOUS PULMONARY VENOUS RETURN", "SCIMITAR SYNDROME"]}
## Clinical Features Auerbach et al. (1981) described recurrent peripheral facial palsy in a brother and sister whose maternal grandfather had had 5 or 6 episodes of unilateral facial weakness, including 3 episodes in 1 year. Inheritance Auerbach et al. (1981) reviewed 3 surveys of cases of facial palsy that reported familial incidences of 2.4, 6.0, and 28.6%. Previous detailed reports of 9 families were reviewed. Danforth (1964) observed 29 cases in 1 kindred; De Santo and Schubert (1969) observed 10 affected in 1 family. Yanagihara et al. (1989) found that of 625 patients with Bell palsy, 26 from 25 families (4%) had a positive family history of same. Family studies suggested autosomal dominant inheritance with low penetrance. The prognosis was generally favorable. There may be heterogeneity in the group of Bell palsy patients, and it is not certain that this is the same disorder as that discussed by Auerbach et al. (1981). Neuro \- Recurrent facial nerve palsy \- Cranial nerve VII palsy Inheritance \- Autosomal dominant ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	FACIAL PALSY, FAMILIAL RECURRENT PERIPHERAL	c1851399	29,139	omim	https://www.omim.org/entry/134200	2019-09-22T16:41:16	{"mesh": ["C565028"], "omim": ["134200"], "orphanet": ["2809"]}
Hereditary condition characterized by muscle wasting This article is about a genetic disorder associated with a defect in the TRPV4 gene. For a list of other conditions with a broadly similar name, see Spinal muscular atrophies. Congenital distal spinal muscular atrophy Other namescongenital dSMA Radiograph showing dysplasia in lower limbs SpecialtyPediatrics, medical genetics Congenital distal spinal muscular atrophy is a hereditary condition characterized by muscle wasting (atrophy), particularly of distal muscles in legs and hands, and by early-onset contractures (permanent shortening of a muscle or joint) of the hip, knee, and ankle. Affected individuals often have shorter lower limbs relative to the trunk and upper limbs. The condition is a result of a loss of anterior horn cells localized to lumbar and cervical regions of the spinal cord early in infancy, which in turn is caused by a mutation of the TRPV4 gene. The disorder is inherited in an autosomal dominant manner.[1] Arm muscle and function, as well as cardiac and respiratory functions are typically well preserved.[2] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Pathophysiology * 3.1 Mechanism * 4 Diagnosis * 5 Management * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (December 2013) (Learn how and when to remove this template message) Lack of muscle, high arch, and hammer toes are indicators of genetic disease * Neurogenic muscle weakness * Atrophy (of lower and upper limbs) * Club foot * Arthrogryposis * Scoliosis * Platyspondyly * Pes cavus * Vocal cord paralysis ## Causes[edit] Congenital distal spinal muscular atrophy is caused by a mutation of the TRPV4 gene found on the 12q23-12q24.1.[3] The mutation causes an affected individual to have lower levels of TRPV4 expression. This deficiency can lead to abnormal osmotic regulation. Congenital dSMA is genetically heterogeneous, meaning a mutation on this gene can cause a plethora of other phenotypically related or phenotypically unrelated diseases depending on the region that is mutated. ## Pathophysiology[edit] The TRPV4 (transient receptor potential vanilloid 4) gene, located on chromosome 12, encodes for a protein that serves as an ion channel, typically found in the plasma membrane and is permeable to Ca2+. Abnormal regulation of Ca2+ can lead to inefficient muscle contraction.[4] TRPV4 plays a major role in mechanosensation, as well as osmosensory functions in nerve endings, endothoelia, and alveoli.[5] The TRPV4 protein consists of 871 amino acids with its N- and C- terminals facing intracellularly. The protein also contains six alpha helices that pass through the plasma membrane. Mutations in TRPV4 can result in the loss of its normal function, or a toxic gain of function. In the latter case, intracellular Ca2+ levels are increased, which results in abnormal regulation.[6] ### Mechanism[edit] The ankyrin repeat domain (ARD) is a region located near the intracellular N-terminal of the TRPV4 protein and consists of six ankyrin repeats. Four missense mutations have been identified at three specific positions all located within the ARD. All of these mutations are due to the swapping out of arginine with a different amino acid.[7] Arginine is highly polar and positively charged, while its replacements are less polar or nonpolar. Some of these identified amino acid substitutions are:[medical citation needed] * R296H, arginine to histidine substitution * R315W, arginine to tryptophan substitution * R316C, arginine to cysteine substitution * R594H, arginine to histidine substitution ## Diagnosis[edit] Denervation atrophy Electrophysiological evidence of denervation with intact motor and sensory nerve conduction findings must be made by using nerve conduction studies, usually in conjunction with EMG. The presence of polyphasic potentials and fibrillation at rest are characteristic of congenital dSMA.[6] The following are useful in diagnosis:[medical citation needed] * Nerve conduction studies (NCS), to test for denervation * Electromyography (EMG), also to detect denervation * X-ray, to look for bone abnormalities * Magnetic resonance imaging (MRI) * Skeletal muscle biopsy examination * Serum creatine kinase (CK) level in blood, usually elevated in affected individuals * Pulmonary function test ## Management[edit] Congenital dSMA has a relatively stable disease course, with disability mainly attributed to increased contractures rather than loss of muscle strength. Individuals frequently use crutches, knee, ankle, and/or foot orthoses, or wheelchairs.[2] Orthopaedic surgery can be an option for some patients with severely impaired movement. Physical therapy and occupational therapy can help prevent further contractures from occurring, though they do not reverse the effects of preexisting ones. Some literature suggests the use of electrical stimulation or botulinum toxin to halt the progression of contractures.[8] ## See also[edit] * Spinal muscular atrophies ## References[edit] 1. ^ Oates EC, Reddel S, Rodriguez ML, et al. (June 2012). "Autosomal dominant congenital spinal muscular atrophy: a true form of spinal muscular atrophy caused by early loss of anterior horn cells". Brain. 135 (Pt 6): 1714–23. doi:10.1093/brain/aws108. PMID 22628388. 2. ^ a b Mercuri E, Messina S, Kinali M, et al. (February 2004). "Congenital form of spinal muscular atrophy predominantly affecting the lower limbs: a clinical and muscle MRI study". Neuromuscul. Disord. 14 (2): 125–9. doi:10.1016/j.nmd.2003.09.005. PMID 14733958. 3. ^ Everaerts W, Nilius B, Owsianik G (September 2010). "The vanilloid transient receptor potential channel TRPV4': from structure to disease". Prog. Biophys. Mol. Biol. 103 (1): 2–17. doi:10.1016/j.pbiomolbio.2009.10.002. PMID 19835908. 4. ^ Menezes MP, North KN (June 2012). "Inherited neuromuscular disorders: pathway to diagnosis". J Paediatr Child Health. 48 (6): 458–65. doi:10.1111/j.1440-1754.2011.02210.x. PMID 22050238. 5. ^ Auer-Grumbach M, Olschewski A, Papić L, et al. (February 2010). "Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C". Nat. Genet. 42 (2): 160–4. doi:10.1038/ng.508. PMC 3272392. PMID 20037588. 6. ^ a b Fiorillo C, Moro F, Brisca G, et al. (August 2012). "TRPV4 mutations in children with congenital distal spinal muscular atrophy". Neurogenetics. 13 (3): 195–203. doi:10.1007/s10048-012-0328-7. PMID 22526352. 7. ^ Dai J, Cho TJ, Unger S, et al. (July 2010). "TRPV4'-pathy, a novel channelopathy affecting diverse systems". J. Hum. Genet. 55 (7): 400–2. doi:10.1038/jhg.2010.37. PMID 20505684. 8. ^ Farmer SE, James M (September 2001). "Contractures in orthopaedic and neurological conditions: a review of causes and treatment". Disabil Rehabil. 23 (13): 549–58. doi:10.1080/09638280010029930. PMID 11451189. ## External links[edit] Classification D * OMIM: 600175 * Connective Tissue Gene Tests (CTGT) * 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Congenital distal spinal muscular atrophy	c1838492	29,140	wikipedia	https://en.wikipedia.org/wiki/Congenital_distal_spinal_muscular_atrophy	2021-01-18T18:59:08	{"mesh": ["C563981"], "omim": ["600175"], "icd-10": ["G12.2"], "orphanet": ["1216"], "synonyms": ["Autosomal dominant benign distal spinal muscular atrophy", "Congenital benign spinal muscular atrophy with contractures", "Congenital nonprogressive spinal muscular atrophy"], "wikidata": ["Q5160420"]}
A number sign (#) is used with this entry because combined oxidative phosphorylation deficiency-3 (COXPD3) is caused by homozygous or compound heterozygous mutation in the TSFM gene (604723) on chromosome 12q14. For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060). Clinical Features Smeitink et al. (2006) reported 2 unrelated patients with COXPD3. The first proband was the child of consanguineous Turkish parents. Muscular hypotonia, sucking weakness, and severe lactic acidosis were the initial clinical signs and symptoms, followed by rhabdomyolysis with elevated creatine kinase values. Generalized convulsions began on the third day of life. Despite intensive treatment, the patient died of progressive encephalomyopathy and respiratory failure at age 7 weeks. The second proband was the offspring of consanguineous Kurdish Jewish parents. The mother reported a paucity of fetal movements throughout pregnancy. At age 36 hours, apathy, irregular breathing, and severe muscular hypotonia were noted. Laboratory investigations revealed severe metabolic acidosis with increased serum lactate level, blood ketone levels, and serum ammonia levels. Echocardiographic examination disclosed severe concentric hypertrophic cardiomyopathy with normal contractility. Death occurred at age 7 weeks. Smits et al. (2011) reported a patient with COXPD3 characterized by onset of lactic acidosis and muscular hypotonia within 3 days after birth and death within the first few months of life. The patient had encephalomyopathy and hypertrophic cardiomyopathy, as well as hepatomegaly. Fibroblasts and muscle tissue showed combined complex I, III, and IV deficiencies. Shamseldin et al. (2012) reported a 2-month-old girl from Chile with intrauterine growth retardation and neonatal hypotonia. She had poor reflexes, poor feeding, and lactic acidosis. Muscle biopsy showed ragged-red fibers, COX deficiency, and decreased activity of mitochondrial complexes I and IV. She died at age 2 months. A previous sib had died of lactic acidosis. Ahola et al. (2014) reported 2 Finnish sisters, born of unrelated parents, with COXPD3. One presented with dilated cardiomyopathy at 10 months of age, and the other with hypertrophic cardiomyopathy at 16 months of age. The cardiac dysfunction resolved over time, and both had stable cardiac function on medication. One patient showed a decline in cognitive function during the school-age years, and brain MRI showed signal intensities in the basal ganglia consistent with Leigh syndrome (LS; 256000). The other patient had mild learning difficulties and normal brain imaging. Both developed optic atrophy with visual impairment as teenagers. At ages 21 and 15 years, respectively, the girls had mild muscle weakness and evidence of a mild axonal sensorimotor neuropathy. The more severely affected girl had frequent dystonic movements. Her muscle biopsy showed combined mitochondrial respiratory defects, with decreased activities of complex I+III (32% of normal) and complex IV (45% of normal). Muscle biopsy of the less severely affected girl showed complex IV deficiency (18% of normal). An unrelated Finnish boy presented at age 15 years with optic neuropathy; brain MRI was normal. He had mild tremor in the trunk and limbs and difficulties with balance, and electrophysiologic studies showed a peripheral axonal neuropathy associated with loss of myelinated axons on sural nerve biopsy. He had no cardiac symptoms and normal cognitive function. Muscle biopsy showed some COX-deficient fibers, but respiratory chain enzyme activities were normal. Ahola et al. (2014) emphasized the phenotypic variability of this disorder and noted that cardiac dysfunction in infancy may improve with time. Molecular Genetics In 2 unrelated patients with COXPD3, Smeitink et al. (2006) identified a homozygous mutation in the TSFM gene (R333W; 604723.0001). The fact that the same mutation was associated with distinct clinical phenotypes suggested that genetic modifiers of the mitochondrial translation apparatus may have been operative. Smits et al. (2011) identified a homozygous R333W mutation in in TSFM in a patient with COXPD3 who was part of a cohort of 27 patients with combined OXPHOS deficiencies. Shamseldin et al. (2012) identified a homozygous R333W mutation in TSFM in a Chilean infant with lethal COXPD3. The mutation was identified by exome sequencing. In 3 Finnish patients from 2 unrelated families with variable clinical manifestations of COXPD3, Ahola et al. (2014) identified compound heterozygous mutations in the TSFM gene (604723.0002-604723.0004). INHERITANCE \- Autosomal recessive GROWTH Other \- Intrauterine growth retardation HEAD & NECK Eyes \- Optic neuropathy \- Optic atrophy \- Visual impairment CARDIOVASCULAR Heart \- Dilated cardiomyopathy (in some patients) \- Concentric hypertrophic cardiomyopathy (in some patients) \- Patent foramen ovale (in some patients) Vascular \- Patent ductus arteriosus (in some patients) RESPIRATORY \- Respiratory failure ABDOMEN Liver \- Hepatomegaly (in some patients) Gastrointestinal \- Poor feeding MUSCLE, SOFT TISSUES \- Hypotonia \- Muscle weakness \- Rhabdomyolysis \- Ragged red fibers seen on muscle biopsy \- COX-deficient fibers NEUROLOGIC Central Nervous System \- Global developmental delay \- Encephalopathy \- Seizures \- Dystonia \- Cognitive impairment \- Tremor \- Ataxia \- Hypotonia, neonatal \- Reduced brain gyri \- Enlarged ventricles \- Abnormal signals in the thalami seen on MRI Peripheral Nervous System \- Axonal sensorimotor neuropathy (in some patients) METABOLIC FEATURES \- Lactic acidosis PRENATAL MANIFESTATIONS Movement \- Decreased fetal movements LABORATORY ABNORMALITIES \- Increased serum lactate \- Increased serum creatine kinase \- Increased serum ketones \- Increased serum ammonia \- Decreased activity of mitochondrial respiratory complexes I, III, and IV MISCELLANEOUS \- Highly variable phenotype MOLECULAR BASIS \- Caused by mutation in the mitochondrial Ts translation elongation factor gene (TSFM, 604723.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 3	c1864840	29,141	omim	https://www.omim.org/entry/610505	2019-09-22T16:04:26	{"doid": ["0060286"], "mesh": ["C566467"], "omim": ["610505"], "orphanet": ["168566"], "synonyms": ["Alternative titles", "ENCEPHALOMYOPATHY, RESPIRATORY FAILURE, AND LACTIC ACIDOSIS", "CONCENTRIC CARDIOMYOPATHY, HYPOTONIA, AND LACTIC ACIDOSIS"]}
The thermal stability of human plasma dopamine-beta-hydroxylase (DBH) shows wide variability. Individuals can be classified into those with thermolabile DBH and those with thermostable DBH. Of 362 unrelated children, 8.01% had thermolabile plasma DBH; of 238 unrelated adults, 5.46% had thermolabile plasma DBH. No correlation with age and sex was noted. Subjects with thermolabile DBH had basal enzyme levels about 55% of those in subjects with stable enzyme. No direct relationship was found between DBH thermolability and the DBH(L) allele, which results in very low basal enzyme activity. The trait of DBH thermolability showed significant familial aggregation, raising the possibility of autosomal recessive inheritance; however, in 3 families in which both parents had thermolabile enzyme, at least 1 offspring with thermostable enzyme was observed. Each of these 'exceptions' had very low basal plasma DBH, due presumably to homozygosity for the DBH(L) allele. The authors suggested that DBH thermolability may be inherited and that there is interaction between the locus for thermostability and that for DBH. Lab \- THermolabile plasma dopamine-beta-hydroxylase (DBH) Inheritance \- Autosomal recessive ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	DOPAMINE BETA-HYDROXYLASE, PLASMA, THERMOLABILITY OF	c1857198	29,142	omim	https://www.omim.org/entry/223380	2019-09-22T16:28:36	{"omim": ["223380"]}
Renpenning syndrome is an X-linked intellectual disability syndrome (XLMR, see this term) characterized by intellectual deficiency, microcephaly, leanness and mild short stature. ## Epidemiology Prevalence is unknown. ## Clinical description The main clinical manifestations of Renpenning syndrome are usually moderate intellectual deficiency, leanness, microcephaly and short stature (relative to familial target measurements) and sometimes small testes (testicular volumes below 15 ml), that are noticed at puberty. Manifestations are expressed only in males, and female carriers show normal facial features, growth development and intelligence. Small head and brain sizes are noted at birth. Characteristic craniofacial features include long triangular faces with upslanting palpebral fissures, half-depilated eyebrows, large ridged or bulbous nose with overhanging columella, short philtrum, and cupped and laterally protruding ears. Patients are thin and show failure to thrive. Delayed motor and language development is noticed in children from an early age. Moderate to severe intellectual deficiency is seen in two thirds of cases. Muscular atrophy is also observed affecting mostly the spine and back muscles resulting in fall of head, upper back curve loss and an appearance of scapula alata. Metacarpophalangeal ankylosis of the thumb and muscular atrophy of the intrinsic muscles of the hand can occur in some cases. Although uncommon, cardiac malformations (atrial septal defect), cleft palate, ocular colobomas and imperforate anus have been noted in a few patients. Phenotypic variants grouped under Renpenning syndrome include Golabi-Ito-Hall syndrome, Hamel cerebro-palato-cardiac syndrome (see these terms), Porteous syndrome, Sutherland-Haan syndrome, MRX55 and three other XLMR families. Hamel cerebro-palato-cardiac syndrome usually has the most severe manifestations. ## Etiology Renpenning syndrome is an X-linked condition caused by mutations in the polyglutamine tract-binding protein 1 (PQBP1) gene, encoding a nuclear protein that regulates pre-mRNA splicing and transcription. Six of the seven mutations discovered in the PQBP1 gene result in a truncated protein whereas a missense mutation that does not affect the length of the mutated protein is seen in Golabi-Ito-Hall syndrome. ## Diagnostic methods Diagnosis is based on inheritance of clinical manifestations of Renpenning syndrome. It is often difficult if there is only one male with intellectual deficiency in a family, but it must be suggested even in sporadic cases. Brain magnetic resonance imaging (MRI) shows no obvious gyral reduction, which contrasts with frank microcephaly. PQBP1 gene screening for a mutation can confirm diagnosis. ## Differential diagnosis Fragile X syndrome is a differential diagnosis but microcephaly is not a feature. Other causes of microcephaly such as fetal CMV infection, fetal alcohol syndrome, maternal phenylketonuria, autosomal recessive microcephalies and Smith-Lemli-Opitz syndrome (see this term) should be considered. ## Antenatal diagnosis If a mutation is identified, prenatal diagnosis may be proposed to parents for further pregnancies. In sporadic cases, germinal mosaicism should be ruled out on prenatal setting. ## Genetic counseling Renpenning syndrome follows an X-linked recessive pattern of inheritance. Genetic testing is possible to identify carrier females and to inform them of the risk of passing on the gene to their offspring. ## Management and treatment Management for Renpenning syndrome involves early education and intervention by trained therapists and treatment of any associated symptoms (cardiac defect, hypospadias, conductive deafness, strabismus). Children need to attend special education courses at school due to learning disabilities. ## Prognosis There is no cure for Renpenning syndrome but in most cases there is no decrease in life expectancy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Renpenning syndrome	c0796135	29,143	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3242	2021-01-23T17:15:50	{"gard": ["9509"], "mesh": ["C537761"], "omim": ["309500"], "icd-10": ["Q87.5"], "synonyms": ["X-linked intellectual disability due to PQBP1 mutations", "X-linked intellectual disability, Renpenning type"]}
Esophageal candidiasis Endoscopic image of esophageal candidiasis in a patient after chemotherapy. Brushings confirmed the presence of hyphae SpecialtyInfectious disease Esophageal candidiasis is an opportunistic infection of the esophagus by Candida albicans. The disease usually occurs in patients in immunocompromised states, including post-chemotherapy and in AIDS. However, it can also occur in patients with no predisposing risk factors, and is more likely to be asymptomatic in those patients.[1] It is also known as candidal esophagitis or monilial esophagitis. ## Contents * 1 Signs and symptoms * 2 Diagnosis * 3 Treatment * 4 References * 5 External links ## Signs and symptoms[edit] People with esophageal candidiasis typically present with difficult or painful swallowing. Longstanding esophageal candidiasis can result in weight loss. There is often concomitant thrush in the mouth. Some patients present with esophageal candidiasis as a first presentation of systemic candidiasis. ## Diagnosis[edit] In most cases, the diagnosis is established based on response to therapy. Patients in whom esophageal candidiasis is suspected should receive a brief course of antifungal therapy with fluconazole. If the infection resolves after treatment with fluconazole, then the diagnosis of esophageal candidiasis is made and no further investigation is needed. However, if the infection persists or if there are other factors involved which may warrant further investigation, then patient will undergo an esophagogastroduodenoscopy if it is safe to do so. Endoscopy often reveals classic diffuse raised plaques that characteristically can be removed from the mucosa by the endoscope. Brushing or biopsy of the plaques shows yeast and pseudohyphae by histology that are characteristic of Candida species. * * * A severe case of candidiasis * H&E stain of esophagus showing Candida hyphae within the lamina propria ## Treatment[edit] The current first-line treatment is fluconazole, 200 mg. on the first day, followed by daily dosing of 100 mg. for at least 21 days total. Treatment should continue for 14 days after relief of symptoms. Other therapy options include: * Nystatin is an effective treatment for mild esophageal candidiasis.[2] It can be used as (swish, do not swallow) treatment for oral candidiasis that occurs with the use of asthma pumps. * Oral fluconazole can be used for moderate to severe esophageal candidiasis (and oropharyngeal candidiasis).[3] * Other oral triazoles, such as itraconazole * Caspofungin, used in refractory or systemic cases * Amphotericin, used in refractory or systemic cases Mimidis, K; Papadopoulos, V; Margaritis, V; Thomopoulos, K; Gatopoulou, A; Nikolopoulou, V; Kartalis, G (February 2005). "Predisposing factors and clinical symptoms in HIV-negative patients with Candida oesophagitis: are they always present?". International Journal of Clinical Practice. 59 (2): 210–3. doi:10.1111/j.1742-1241.2004.00249.x. PMID 15854199. ## References[edit] 1. ^ Mimidis, K; Papadopoulos, V; Margaritis, V; Thomopoulos, K; Gatopoulou, A; Nikolopoulou, V; Kartalis, G (February 2005). "Predisposing factors and clinical symptoms in HIV-negative patients with Candida oesophagitis: are they always present?". International Journal of Clinical Practice. 59 (2): 210–3. doi:10.1111/j.1742-1241.2004.00249.x. PMID 15854199. 2. ^ Gary W. Falk, David A. Katzka, in Goldman's Cecil Medicine (Twenty Fourth Edition), 2012, Diseases of the Esophagus 3. ^ 2 ## External links[edit] Classification D * ICD-9-CM: 112.84 * v * t * e Fungal infection and mesomycetozoea Superficial and cutaneous (dermatomycosis): Tinea = skin; Piedra (exothrix/ endothrix) = hair Ascomycota Dermatophyte (Dermatophytosis) By location * Tinea barbae/tinea capitis * Kerion * Tinea corporis * Ringworm * Dermatophytids * Tinea cruris * Tinea manuum * Tinea pedis (athlete's foot) * Tinea unguium/onychomycosis * White superficial onychomycosis * Distal subungual onychomycosis * Proximal subungual onychomycosis * Tinea corporis gladiatorum * Tinea faciei * Tinea imbricata * Tinea incognito * Favus By organism * Epidermophyton floccosum * Microsporum canis * Microsporum audouinii * Trichophyton interdigitale/mentagrophytes * Trichophyton tonsurans * Trichophyton schoenleini * Trichophyton rubrum * Trichophyton verrucosum Other * Hortaea werneckii * Tinea nigra * Piedraia hortae * Black piedra Basidiomycota * Malassezia furfur * Tinea versicolor * Pityrosporum folliculitis * Trichosporon * White piedra Subcutaneous, systemic, and opportunistic Ascomycota Dimorphic (yeast+mold) Onygenales * Coccidioides immitis/Coccidioides posadasii * Coccidioidomycosis * Disseminated coccidioidomycosis * Primary cutaneous coccidioidomycosis. Primary pulmonary coccidioidomycosis * Histoplasma capsulatum * Histoplasmosis * Primary cutaneous histoplasmosis * Primary pulmonary histoplasmosis * Progressive disseminated histoplasmosis * Histoplasma duboisii * African histoplasmosis * Lacazia loboi * Lobomycosis * Paracoccidioides brasiliensis * Paracoccidioidomycosis Other * Blastomyces dermatitidis * Blastomycosis * North American blastomycosis * South American blastomycosis * Sporothrix schenckii * Sporotrichosis * Talaromyces marneffei * Talaromycosis Yeast-like * Candida albicans * Candidiasis * Oral * Esophageal * Vulvovaginal * Chronic mucocutaneous * Antibiotic candidiasis * Candidal intertrigo * Candidal onychomycosis * Candidal paronychia * Candidid * Diaper candidiasis * Congenital cutaneous candidiasis * Perianal candidiasis * Systemic candidiasis * Erosio interdigitalis blastomycetica * C. auris * C. glabrata * C. lusitaniae * C. tropicalis * Pneumocystis jirovecii * Pneumocystosis * Pneumocystis pneumonia Mold-like * Aspergillus * Aspergillosis * Aspergilloma * Allergic bronchopulmonary aspergillosis * Primary cutaneous aspergillosis * Exophiala jeanselmei * Eumycetoma * Fonsecaea pedrosoi/Fonsecaea compacta/Phialophora verrucosa * Chromoblastomycosis * Geotrichum candidum * Geotrichosis * Pseudallescheria boydii * Allescheriasis Basidiomycota * Cryptococcus neoformans * Cryptococcosis * Trichosporon spp * Trichosporonosis Zygomycota (Zygomycosis) Mucorales (Mucormycosis) * Rhizopus oryzae * Mucor indicus * Lichtheimia corymbifera * Syncephalastrum racemosum * Apophysomyces variabilis Entomophthorales (Entomophthoramycosis) * Basidiobolus ranarum * Basidiobolomycosis * Conidiobolus coronatus/Conidiobolus incongruus * Conidiobolomycosis Microsporidia (Microsporidiosis) * Enterocytozoon bieneusi/Encephalitozoon intestinalis Mesomycetozoea * Rhinosporidium seeberi * Rhinosporidiosis Ungrouped * Alternariosis * Fungal folliculitis * Fusarium * Fusariosis * Granuloma gluteale infantum * Hyalohyphomycosis * Otomycosis * Phaeohyphomycosis * v * t * e Diseases of the digestive system Upper GI tract Esophagus * Esophagitis * Candidal * Eosinophilic * Herpetiform * Rupture * Boerhaave syndrome * Mallory–Weiss syndrome * UES * Zenker's diverticulum * LES * Barrett's esophagus * Esophageal motility disorder * Nutcracker esophagus * Achalasia * Diffuse esophageal spasm * Gastroesophageal reflux disease (GERD) * Laryngopharyngeal reflux (LPR) * Esophageal stricture * Megaesophagus * Esophageal intramural pseudodiverticulosis Stomach * Gastritis * Atrophic * Ménétrier's disease * Gastroenteritis * Peptic (gastric) ulcer * Cushing ulcer * Dieulafoy's lesion * Dyspepsia * Pyloric stenosis * Achlorhydria * Gastroparesis * Gastroptosis * Portal hypertensive gastropathy * Gastric antral vascular ectasia * Gastric dumping syndrome * Gastric volvulus * Buried bumper syndrome * Gastrinoma * Zollinger–Ellison syndrome Lower GI tract Enteropathy Small intestine (Duodenum/Jejunum/Ileum) * Enteritis * Duodenitis * Jejunitis * Ileitis * Peptic (duodenal) ulcer * Curling's ulcer * Malabsorption: Coeliac * Tropical sprue * Blind loop syndrome * Small bowel bacterial overgrowth syndrome * Whipple's * Short bowel syndrome * Steatorrhea * Milroy disease * Bile acid malabsorption Large intestine (Appendix/Colon) * Appendicitis * Colitis * Pseudomembranous * Ulcerative * Ischemic * Microscopic * Collagenous * Lymphocytic * Functional colonic disease * IBS * Intestinal pseudoobstruction / Ogilvie syndrome * Megacolon / Toxic megacolon * Diverticulitis/Diverticulosis/SCAD Large and/or small * Enterocolitis * Necrotizing * Gastroenterocolitis * IBD * Crohn's disease * Vascular: Abdominal angina * Mesenteric ischemia * Angiodysplasia * Bowel obstruction: Ileus * Intussusception * Volvulus * Fecal impaction * Constipation * Diarrhea * Infectious * Intestinal adhesions Rectum * Proctitis * Radiation proctitis * Proctalgia fugax * Rectal prolapse * Anismus Anal canal * Anal fissure/Anal fistula * Anal abscess * Hemorrhoid * Anal dysplasia * Pruritus ani GI bleeding * Blood in stool * Upper * Hematemesis * Melena * Lower * Hematochezia Accessory Liver * Hepatitis * Viral hepatitis * Autoimmune hepatitis * Alcoholic hepatitis * Cirrhosis * PBC * Fatty liver * NASH * Vascular * Budd–Chiari syndrome * Hepatic veno-occlusive disease * Portal hypertension * Nutmeg liver * Alcoholic liver disease * Liver failure * Hepatic encephalopathy * Acute liver failure * Liver abscess * Pyogenic * Amoebic * Hepatorenal syndrome * Peliosis hepatis * Metabolic disorders * Wilson's disease * Hemochromatosis Gallbladder * Cholecystitis * Gallstone / Cholelithiasis * Cholesterolosis * Adenomyomatosis * Postcholecystectomy syndrome * Porcelain gallbladder Bile duct/ Other biliary tree * Cholangitis * Primary sclerosing cholangitis * Secondary sclerosing cholangitis * Ascending * Cholestasis/Mirizzi's syndrome * Biliary fistula * Haemobilia * Common bile duct * Choledocholithiasis * Biliary dyskinesia * Sphincter of Oddi dysfunction Pancreatic * Pancreatitis * Acute * Chronic * Hereditary * Pancreatic abscess * Pancreatic pseudocyst * Exocrine pancreatic insufficiency * Pancreatic fistula Other Hernia * Diaphragmatic * Congenital * Hiatus * Inguinal * Indirect * Direct * Umbilical * Femoral * Obturator * Spigelian * Lumbar * Petit's * Grynfeltt-Lesshaft * Undefined location * Incisional * Internal hernia * Richter's Peritoneal * Peritonitis * Spontaneous bacterial peritonitis * Hemoperitoneum * Pneumoperitoneum [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Esophageal candidiasis	c0239295	29,144	wikipedia	https://en.wikipedia.org/wiki/Esophageal_candidiasis	2021-01-18T18:51:51	{"umls": ["C0239295"], "wikidata": ["Q5398631"]}
A number sign (#) is used with this entry because of evidence that essential fructosuria is caused by compound heterozygous mutation in the KHK gene (614058) on chromosome 2p23. Description Essential fructosuria is a benign, asymptomatic defect of intermediary metabolism characterized by the intermittent appearance of fructose in the urine (summary by Bonthron et al., 1994). Clinical Features In individuals with essential fructosuria, ingestion of dietary fructose, sucrose, or sorbitol is followed by an abnormally large and persistent rise in blood fructose concentration and by excretion of 10 to 20% of the ingested load in the urine (Gitzelmann et al., 1989). Essential fructosuria was first described independently by Czapek (1876) and Zimmer (1876) in a man who also suffered from diabetes mellitus. Laron (1961) counted 50 published cases, of which 18 were in Jews. The enzyme deficiency was demonstrated in liver by Schapira et al. (1961). Khachadurian (1963) described nonalimentary fructosuria in an 18-month-old Arab boy who suffered from sickle-cell thalassemia. The fructose tolerance test was normal and fructosuria persisted after fructose was entirely excluded from the diet, but had decreased markedly when the patient was seen 2 years later. Both the spleen and the liver were enlarged. The patient's parents were first cousins. Urine samples from both parents were negative for a reducing substance. Urine samples from the brother and 2 sisters showed intermittent fructosuria. Small amounts of fructose occur in the urine of normal individuals ingesting a regular diet but amounts sufficient to give a positive test for reducing sugar in the routine examination occur only in essential fructosuria, familial fructose intolerance, and advanced liver disease. Using (31)P magnetic resonance spectroscopy to measure changes in liver metabolite concentrations in adults with fructosuria, Boesiger et al. (1994) found that concentrations of fructose-1-phosphate, ATP, and inorganic phosphate remained unchanged, confirming that fructokinase was indeed inactive. Inheritance Lasker (1941) documented autosomal recessive inheritance of essential fructosuria. Molecular Genetics In a well-characterized family in which 3 of 8 sibs had fructosuria (Steinmann and Gitzelmann, 1981; Gitzelmann et al., 1989; Boesiger et al., 1994), Bonthron et al. (1994) found that all affected individuals were compound heterozygous for 2 mutations in the KHK gene: gly40-to-arg (614058.0001) and ala43-to-thr (614058.0002). Both mutations resulted from a G-to-A transition, and each altered the same conserved region of the KHK protein. Neither mutation was seen in a sample of 52 unrelated control individuals. INHERITANCE \- Autosomal recessive LABORATORY ABNORMALITIES \- Fructosuria MISCELLANEOUS \- Benign, asymptomatic defect MOLECULAR BASIS \- Caused by mutation in the ketohexokinase gene (KHK, 614058.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	FRUCTOSURIA, ESSENTIAL	c0268160	29,145	omim	https://www.omim.org/entry/229800	2019-09-22T16:27:42	{"mesh": ["C538068"], "omim": ["229800"], "icd-10": ["E74.11"], "orphanet": ["2056"], "synonyms": ["Alternative titles", "HEPATIC FRUCTOKINASE DEFICIENCY", "KETOHEXOKINASE DEFICIENCY"]}
Urinary incontinence Other namesInvoluntary urination SpecialtyUrology, gynecology Urinary incontinence (UI), also known as involuntary urination, is any uncontrolled leakage of urine. It is a common and distressing problem, which may have a large impact on quality of life.[1] It has been identified as an important issue in geriatric health care.[2] The term enuresis is often used to refer to urinary incontinence primarily in children, such as nocturnal enuresis (bed wetting).[3] Pelvic surgery, pregnancy, childbirth, and menopause are major risk factors.[4] Urinary incontinence is often a result of an underlying medical condition but is under-reported to medical practitioners.[5] There are four main types of incontinence:[6] * Urge incontinence due to an overactive bladder * Stress incontinence due "a poorly functioning urethral sphincter muscle (intrinsic sphincter deficiency) or to hypermobility of the bladder neck or urethra"[7] * Overflow incontinence due to either poor bladder contraction or blockage of the urethra * Mixed incontinence involve features of different other types Treatments include pelvic floor muscle training, bladder training, surgery, and electrical stimulation.[8] Behavioral therapy generally works better than medication for stress and urge incontinence.[9] The benefit of medications is small and long term safety is unclear.[8] Urinary incontinence is more common in older women.[10] ## Contents * 1 Causes * 1.1 Women * 1.2 Men * 1.3 Both * 2 Mechanism * 2.1 Adults * 2.2 Children * 3 Diagnosis * 3.1 Main types * 3.2 Other types * 3.3 Screening * 4 Management * 4.1 Behavioral therapy * 4.1.1 Lifestyle changes * 4.1.2 Exercises * 4.2 Devices * 4.3 Medications * 4.4 Surgery * 4.5 Injectable treatment * 5 Epidemiology * 5.1 Women * 5.2 Men * 5.3 Children * 6 History * 7 Research * 8 References * 9 External links ## Causes[edit] Urinary incontinence can result from both urologic and non-urologic causes. Urologic causes can be classified as either bladder dysfunction or urethral sphincter incompetence and may include detrusor overactivity, poor bladder compliance, urethral hypermobility, or intrinsic sphincter deficiency. Non-urologic causes may include infection, medication or drugs, psychological factors, polyuria, stool impaction, and restricted mobility.[11] The causes leading to urinary incontinence are usually specific to each sex, however, some causes are common to both men and women. ### Women[edit] Pelvic floor muscles in women The most common types of urinary incontinence in women are stress urinary incontinence and urge urinary incontinence. Women that have symptoms from both types are said to have "mixed" urinary incontinence. After menopause, estrogen production decreases and, in some women, urethral tissue will demonstrate atrophy, becoming weaker and thinner, possibly playing a role in the development of urinary incontinence.[4] Stress urinary incontinence in women is most commonly caused by loss of support of the urethra, which is usually a consequence of damage to pelvic support structures as a result of pregnancy, childbirth, obesity, age, among others.[12] About 33% of all women experience urinary incontinence after giving birth, and women who deliver vaginally are about twice as likely to have urinary incontinence as women who give birth via a Caesarean section.[13] Stress incontinence is characterized by leaking of small amounts of urine with activities that increase abdominal pressure such as coughing, sneezing, laughing and lifting. This happens when the urethral sphincter cannot close completely due to the damage in the sphincter itself, or the surrounding tissue. Additionally, frequent exercise in high-impact activities can cause athletic incontinence to develop. Urge urinary incontinence, is caused by uninhibited contractions of the detrusor muscle, a condition known as overactive bladder syndrome. It is characterized by leaking of large amounts of urine in association with insufficient warning to get to the bathroom in time. ### Men[edit] The prostate with the urethra passing through it (prostatic urethra) Urge incontinence is the most common type of incontinence in men.[14] Similar to women, urine leakage happens following a very intense feeling of urination, not allowing enough time to reach the bathroom, a condition called overactive bladder syndrome. In men, the condition is commonly associated with benign prostatic hyperplasia (an enlarged prostate), which causes bladder outlet obstruction, a dysfunction of the detrusor muscle (muscle of the bladder), eventually causing overactive bladder syndrome, and the associated incontinence.[14] Stress urinary incontinence is the other common type of incontinence in men, and it most commonly happens after prostate surgery.[15] Prostatectomy, transurethral resection of the prostate, prostate brachytherapy, and radiotherapy can all damage the urethral sphincter and surrounding tissue, causing it to be incompetent. An incompetent urethral sphincter cannot prevent the urine from leaking out of the urinary bladder during activities that increase the intraabdominal pressure, such as coughing, sneezing, or laughing. Continence usually improves within 6 to 12 months after prostate surgery without any specific interventions, and only 5 to 10% of people report persistent symptoms.[14] ### Both[edit] * Age is a risk factor that increases both the severity and prevalence of UI * Polyuria (excessive urine production) of which, in turn, the most frequent causes are: uncontrolled diabetes mellitus, primary polydipsia (excessive fluid drinking), central diabetes insipidus and nephrogenic diabetes insipidus.[16] Polyuria generally causes urinary urgency and frequency, but does not necessarily lead to incontinence. * Neurogenic disorders like multiple sclerosis, spina bifida, Parkinson's disease, strokes and spinal cord injury can all interfere with nerve function of the bladder.[17] This can lead to neurogenic bladder dysfunction * Overactive bladder syndrome. However, the etiology behind this is usually different between men and women, as mentioned above. * Other suggested risk factors include smoking, caffeine intake and depression ## Mechanism[edit] Anatomy of the lower urinary tract and genital system ### Adults[edit] The body stores urine — water and wastes removed by the kidneys — in the urinary bladder, a balloon-like organ. The bladder connects to the urethra, the tube through which urine leaves the body. Continence and micturition involve a balance between urethral closure and detrusor muscle activity (the muscle of the bladder). During urination, detrusor muscles in the wall of the bladder contract, forcing urine out of the bladder and into the urethra. At the same time, sphincter muscles surrounding the urethra relax, letting urine pass out of the body. The urethral sphincter is the muscular ring that closes the outlet of the urinary bladder preventing urine to pass outside the body. Urethral pressure normally exceeds bladder pressure, resulting in urine remaining in the bladder, and maintaining continence.[18] The urethra is supported by pelvic floor muscles and tissue, allowing it to close firmly. Any damage to this balance between the detrusor muscle, urethral sphincter, supportive tissue and nerves can lead to some type of incontinence . For example, stress urinary incontinence is usually a result of the incompetent closure of the urethral sphincter. This can be caused by damage to the sphincter itself, the muscles that support it, or nerves that supply it. In men, the damage usually happens after prostate surgery or radiation,[14] and in women, it's usually caused by childbirth and pregnancy.[19] The pressure inside the abdomen (from coughing and sneezing) is normally transmitted to both urethra and bladder equally, leaving the pressure difference unchanged, resulting in continence. When the sphincter is incompetent, this increase in pressure will push the urine against it, leading to incontinence. Another example is urge incontinence. This incontinence is associated with sudden forceful contractions of the detrusor muscle (bladder muscle), leading to an intense feeling of urination, and incontinence if the person does not reach the bathroom on time. The syndrome is known as overactive bladder syndrome, and it's related to dysfunction of the detrusor muscle.[20] ### Children[edit] Voiding dysfunction Main article: Enuresis Urination, or voiding, is a complex activity. The bladder is a balloon-like muscle that lies in the lowest part of the abdomen. The bladder stores urine then releases it through the urethra, the canal that carries urine to the outside of the body. Controlling this activity involves nerves, muscles, the spinal cord and the brain. The bladder is made of two types of muscles: the detrusor, a muscular sac that stores urine and squeezes to empty, and the sphincter, a circular group of muscles at the bottom or neck of the bladder that automatically stay contracted to hold the urine in and automatically relax when the detrusor contracts to let the urine into the urethra. A third group of muscles below the bladder (pelvic floor muscles) can contract to keep urine back. A baby's bladder fills to a set point, then automatically contracts and empties. As the child gets older, the nervous system develops. The child's brain begins to get messages from the filling bladder and begins to send messages to the bladder to keep it from automatically emptying until the child decides it is the time and place to void. Failures in this control mechanism result in incontinence. Reasons for this failure range from the simple to the complex. ## Diagnosis[edit] Ultrasound of the urinary bladder of an 85-year-old man. It shows a trabeculated wall, which is a sign of urinary retention. The pattern of voiding and urine leakage is important as it suggests the type of incontinence. Other points include straining and discomfort, use of drugs, recent surgery, and illness. The physical examination looks for signs of medical conditions causing incontinence, such as tumors that block the urinary tract, stool impaction, and poor reflexes or sensations, which may be evidence of a nerve-related cause. Other tests include:[21] * Stress test – the patient relaxes, then coughs vigorously as the doctor watches for loss of urine. * Urinalysis – urine is tested for evidence of infection, urinary stones, or other contributing causes. * Blood tests – blood is taken, sent to a laboratory, and examined for substances related to causes of incontinence. * Ultrasound – sound waves are used to visualize the kidneys and urinary bladder, assess the capacity of the bladder before voiding, and the remaining amount of urine after voiding. This helps know if there's a problem in emptying. * Cystoscopy – a thin tube with a tiny camera is inserted in the urethra and used to see the inside of the urethra and bladder. * Urodynamics – various techniques measure pressure in the bladder and the flow of urine. People are often asked to keep a diary for a day or more, up to a week, to record the pattern of voiding, noting times and the amounts of urine produced. Research projects that assess the efficacy of anti-incontinence therapies often quantify the extent of urinary incontinence. The methods include the 1-h pad test, measuring leakage volume; using a voiding diary, counting the number of incontinence episodes (leakage episodes) per day; and assessing of the strength of pelvic floor muscles, measuring the maximum vaginal squeeze pressure. ### Main types[edit] There are 4 main types of urinary incontinence: * Stress incontinence, also known as effort incontinence, is essentially due to incomplete closure of the urinary sphincter, due to problems in the sphincter itself or insufficient strength of the pelvic floor muscles supporting it. This type of incontinence is when urine leaks during activities that increase intra-abdominal pressure, such as coughing, sneezing, or bearing down. * Urge incontinence is an involuntary loss of urine occurring while suddenly feeling the need or urge to urinate, usually secondary to overactive bladder syndrome. * Overflow incontinence is the incontinence that happens suddenly without feeling an urge to urinate and without necessarily doing any physical activities. It is also known as under-active bladder syndrome. This usually happens with chronic obstruction of the bladder outlet or with diseases damaging the nerves supplying the urinary bladder. The urine stretches the bladder without the person feeling the pressure, and eventually, it overwhelms the ability of the urethral sphincter to hold it back.[22] * Mixed incontinence contains symptoms of multiple other types of incontinence. It is not uncommon in the elderly female population and can sometimes be complicated by urinary retention. ### Other types[edit] * Functional incontinence occurs when a person recognizes the need to urinate but cannot make it to the bathroom. The loss of urine may be large. There are several causes of functional incontinence including confusion, dementia, poor eyesight, mobility or dexterity, unwillingness to the toilet because of depression or anxiety or inebriation due to alcohol.[23] Functional incontinence can also occur in certain circumstances where no biological or medical problem is present. For example, a person may recognize the need to urinate but may be in a situation where there is no toilet nearby or access to a toilet is restricted. * Structural incontinence: Rarely, structural problems can cause incontinence, usually diagnosed in childhood (for example, an ectopic ureter). Fistulas caused by obstetric and gynecologic trauma or injury are commonly known as obstetric fistulas and can lead to incontinence. These types of vaginal fistulas include, most commonly, vesicovaginal fistula and, more rarely, ureterovaginal fistula. These may be difficult to diagnose. The use of standard techniques along with a vaginogram or radiologically viewing the vaginal vault with instillation of contrast media.[24] * Nocturnal enuresis is episodic UI while asleep. It is normal in young children. * Transient incontinence is temporary incontinence most often seen in pregnant women when it subsequently resolves after the birth of the child.[25] * Giggle incontinence is an involuntary response to laughter. It usually affects children. * Double incontinence. There is also a related condition for defecation known as fecal incontinence. Due to involvement of the same muscle group (levator ani) in bladder and bowel continence, patients with urinary incontinence are more likely to have fecal incontinence in addition.[26] This is sometimes termed "double incontinence". * Post-void dribbling is the phenomenon where urine remaining in the urethra after voiding the bladder slowly leaks out after urination. * Coital incontinence (CI) is urinary leakage that occurs during either penetration or orgasm and can occur with a sexual partner or with masturbation. It has been reported to occur in 10% to 24% of sexually active women with pelvic floor disorders.[27] * Climacturia is urinary incontinence at the moment of orgasm. It can be a result of radical prostatectomy. ### Screening[edit] Yearly screening is recommended for women by the Women's Preventive Services Initiative. Screening questions should inquire about what symptoms they have experienced, how severe the symptoms are, and if the symptoms affect their daily lives.[28] As of 2018, studies have not shown a change in outcomes with urinary incontinence screenings in women.[29] ## Management[edit] Treatment options range from conservative treatment, behavioral therapy, bladder retraining,[30] pelvic floor therapy, collecting devices (for men), fixer-occluder devices for incontinence (in men), medications and surgery.[31] A 2018 systematic review confirms that several nonsurgical treatments can improve or even stop UI in women.[32] The success of treatment depends on the correct diagnoses.[33] ### Behavioral therapy[edit] Behavioral therapy involves the use of both suppressive techniques (distraction, relaxation) and learning to avoid foods that may worsen urinary incontinence. This may involve avoiding or limiting consumption of caffeine and alcohol. Behavioral therapies, including bladder training, biofeedback, and pelvic floor muscle training, are most effective for improving urinary incontinence in women, with a low risk of adverse events.[34] Behavioral therapy is not curative for urinary incontinence, but it can improve a person's quality of life. Behavioral therapy has benefits as both a monotherapy and as an adjunct to medications for symptom reduction.[35] #### Lifestyle changes[edit] Avoiding heavy lifting and preventing constipation may help with uncontrollable urine leakage. Stopping smoking is also recommended as it is associated with improvements in urinary incontinence in men and women.[36] Weight loss is recommended in those who are obese.[37] #### Exercises[edit] Exercising the muscles of the pelvis such as with Kegel exercises are a first line treatment for women with stress incontinence.[37] Efforts to increase the time between urination, known as bladder training, is recommended in those with urge incontinence.[37] Both these may be used in those with mixed incontinence.[37] Small vaginal cones of increasing weight may be used to help with exercise.[38][39] They seem to be better than no active treatment in women with stress urinary incontinence, and have similar effects to training of pelvic floor muscles or electrostimulation.[39] Biofeedback uses measuring devices to help the patient become aware of his or her body's functioning. By using electronic devices or diaries to track when the bladder and urethral muscles contract, the patient can gain control over these muscles. Biofeedback can be used with pelvic muscle exercises and electrical stimulation to relieve stress and urge incontinence. Time voiding while urinating and bladder training are techniques that use biofeedback. In time voiding, the patient fills in a chart of voiding and leaking. From the patterns that appear in the chart, the patient can plan to empty his or her bladder before he or she would otherwise leak. Biofeedback and muscle conditioning, known as bladder training, can alter the bladder's schedule for storing and emptying urine. These techniques are effective for urge and overflow incontinence[40] A 2013 randomized controlled trial found no benefit of adding biofeedback to pelvic floor muscle exercise in stress urinary incontinence, but observing improvements in both groups.[41][non-primary source needed] In another randomized controlled trial the addition of biofeedback to the training of pelvic floor muscles for the treatment of stress incontinence, improved pelvic floor muscle function, reduced urinary symptoms, and improved the quality of life.[42][non-primary source needed] Preoperative pelvic floor muscle training (PFMT) in men undergoing radical prostatectomy was not effective in reducing urinary incontinence.[15] Alternative exercises have been studied for stress urinary incontinence in women.[43] Evidence was insufficient to support the use of Paula method, abdominal muscle training, Pilates, Tai Chi, breathing exercises, postural training, and generalized fitness.[43] ### Devices[edit] Example of a foley catheter Individuals who continue to experience urinary incontinence need to find a management solution that matches their individual situation. The use of mechanical devices has not been well studied in women, as of 2014.[44] * Collecting systems (for men) – consists of a sheath worn over the penis funneling the urine into a urine bag worn on the leg. These products come in a variety of materials and sizes for individual fit. Studies [45] show that urisheaths and urine bags are preferred over absorbent products – in particular when it comes to ‘limitations to daily activities’. Solutions exist for all levels of incontinence. Advantages with collecting systems are that they are discreet, the skin stays dry all the time, and they are convenient to use both day and night. Disadvantages are that it is necessary to get measured to ensure proper fit, and in some countries a prescription is needed. * Absorbent products (include shields, incontinence pads, undergarments, protective underwear, briefs, diapers, adult diapers and underpants) are the best-known product types to manage incontinence. They are widely available in pharmacies and supermarkets. The advantages of using these are that they barely need any fitting or introduction by a health-care specialist. The disadvantages with absorbent products are that they can be bulky, leak, have odors and can cause skin breakdown due to the constant dampness. * Intermittent catheters are single-use catheters that are inserted into the bladder to empty it, and once the bladder is empty they are removed and discarded. Intermittent catheters are primarily used for urinary retention (inability to empty the bladder), but for some people they can be used to reduce or avoid incontinence. These are prescription-only medical devices. * Different types of pessaries. These are inserted inside the vagina for support. Indwelling catheters (also known as foleys) are often used in hospital settings, or if the user is not able to handle any of the above solutions himself/herself (e.g. severe neurologic injury or neurodegenerative disease). These are also prescription-only medical devices. The indwelling catheter is typically connected to a urine bag that can be worn on the leg or hung on the side of the bed. Indwelling catheters need to be monitored and changed on a regular basis by a health-care professional. The advantage of indwelling catheters is that because the urine is funneled away from the body, the skin remains dry. However, the disadvantage is that it is very common to incur urinary-tract infections when using indwelling catheters. Bladder spasms and other problems can also occur with long-term use of indwelling catheters.[46] * Penis clamp (or penis compression device), which is applied to compress the urethra to compensate for the malfunctioning of the natural urinary sphincter, preventing leakage from the bladder.[47] This management solution is only suitable for light or moderate incontinence. * Vaginal pessaries for women are devices inserted into the vagina. This device provides support to the urethra which passes right in front of it, allowing it to close more firmly. ### Medications[edit] A number of medications exist to treat urinary incontinence including: fesoterodine, tolterodine and oxybutynin.[48] These medications work by relaxing smooth muscle in the bladder.[49][50][51] While some of these medications appear to have a small benefit, the risk of side effects are a concern.[48] Medications are effective for about one in ten people, and all medications have similar efficacy.[48] Medications are not recommended for those with stress incontinence and are only recommended in those with urge incontinence who do not improve with bladder training.[37] ### Surgery[edit] Women and men that have persistent incontinence despite optimal conservative therapy may be candidates for surgery. Surgery may be used to help stress or overflow incontinence.[6] Common surgical techniques for stress incontinence include slings, tension-free vaginal tape, bladder suspension, artificial urinary sphincters, among others.[6] The use of transvaginal mesh implants and bladder slings is controversial due to the risk of debilitating painful side effects such as vaginal erosion.[52] In 2012 transvaginal mesh implants were classified as a high risk device by the US Food and Drug Administration.[53] Urodynamic testing seems to confirm that surgical restoration of vault prolapse can cure motor urge incontinence. Traditional suburethral sling operations are probably slightly better than open abdominal retropubic colposuspension and are probably slightly less effective than mid-urethral sling operations in reducing urinary incontinence in women, but it is still uncertain if any of the different types of traditional suburethral sling operations are better than others.[54] Similarly, there is insufficient evidence to be certain about the effectiveness or safety of single-incision sling operations for urinary incontinence in women.[55] Traditional suburethal slings may have a higher risk of surgical complications than minimally invasive slings but the risk of complications compared with other types of operation is still uncertain.[54] Laparoscopic colposuspension (keyhole surgery through the abdomen) with sutures is as effective as open colposuspension for curing incontinence in women up to 18 months after surgery, but it is unclear whether there are fewer risk of complications during or after surgery.[56] There is probably a higher risk of complications with traditional suburethral slings than with open abdominal retropubic suspension.[56] AMS 800 and ZSI 375 artificial urinary sphincters The artificial urinary sphincter (AUS) is an implantable device used to treat stress incontinence, mostly in men. The device is made of 2 or 3 parts: The pump, cuff, and balloon reservoir, connected to each other by specialized tubes. The cuff wraps around the urethra and closes it. When the person wants to urinate, he presses the pump (implanted in the scrotum), to deflate the cuff, and allow the urine to pass. The cuff regains pressure within a few minutes to regain continence.[57] The European Association of Urology considers the AUS as the gold standard in surgical management of stress urinary incontinence in men after prostatectomy.[58] ### Injectable treatment[edit] Injectable bulking agents may be used to enhance urethral support, however, they are of unclear benefit.[59][60] ## Epidemiology[edit] Globally, up to 35% of the population over the age of 60 years is estimated to be incontinent.[61] In 2014, urinary leakage affected between 30% and 40% of people over 65 years of age living in their own homes or apartments in the U.S.[62] Twenty-four percent of older adults in the U.S. have moderate or severe urinary incontinence that should be treated medically.[62] Bladder control problems have been found to be associated with higher incidence of many other health problems such as obesity and diabetes. Difficulty with bladder control results in higher rates of depression and limited activity levels.[63] Incontinence is expensive both to individuals in the form of bladder control products and to the health care system and nursing home industry. Injury related to incontinence is a leading cause of admission to assisted living and nursing care facilities. In 1997 more than 50% of nursing facility admissions were related to incontinence.[64] ### Women[edit] Bladder symptoms affect women of all ages. However, bladder problems are most prevalent among older women.[65] Women over the age of 60 years are twice as likely as men to experience incontinence; one in three women over the age of 60 years are estimated to have bladder control problems.[61] One reason why women are more affected is the weakening of pelvic floor muscles by pregnancy.[66] ### Men[edit] Men tend to experience incontinence less often than women, and the structure of the male urinary tract accounts for this difference. Stress incontinence is common after prostate cancer treatments. While urinary incontinence affects older men more often than younger men, the onset of incontinence can happen at any age. Estimates in the mid-2000s suggested that 17 percent of men over age 60, an estimated 600,000 men,[where?] experienced urinary incontinence, with this percentage increasing with age.[67] ### Children[edit] Incontinence happens less often after age 5: About 10 percent of 5-year-olds, 5 percent of 10-year-olds, and 1 percent of 18-year-olds experience episodes of incontinence. It is twice as common in girls as in boys.[68] ## History[edit] The management of urinary incontinence with pads is mentioned in the earliest medical book known, the Ebers Papyrus (1500 BC).[69] Incontinence has historically been a taboo subject in Western culture. However, this situation changed some when Kimberly-Clark aggressively marketed adult diapers in the 1980s with actor June Allyson as spokeswoman. Allyson was initially reticent to participate, but her mother, who had incontinence, convinced her that it was her duty in light of her successful career. The product proved a success.[70] ## Research[edit] The effectiveness of different therapeutic approaches to treating urinary incontinence is not well studied for some medical conditions. For example, for people who experience urinary incontinence due to stroke, treatment approaches such as physical therapy, cognitive therapy, complementary medicine, and specialized interventions with experienced medical professionals are sometimes suggested, however it is not clear how effective these are at improving incontinence and there is no strong medical evidence to guide clinical practice.[17] ## References[edit] 1. ^ Ackley B (2010). Nursing diagnosis handbook : an evidence-based guide to planning care (9th ed.). Maryland Heights, Mo: Mosby. ISBN 9780323071505. 2. ^ Venes D (2013). Taber's cyclopedic medical dictionary. Philadelphia: F.A. 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Retrieved 23 August 2014. 63. ^ Nygaard I, Turvey C, Burns TL, Crischilles E, Wallace R (January 2003). "Urinary incontinence and depression in middle-aged United States women". Obstetrics and Gynecology. 101 (1): 149–56. doi:10.1016/s0029-7844(02)02519-x. PMID 12517660. 64. ^ Thom DH, Haan MN, Van Den Eeden SK (September 1997). "Medically recognized urinary incontinence and risks of hospitalization, nursing home admission and mortality". Age and Ageing. 26 (5): 367–74. doi:10.1093/ageing/26.5.367. PMID 9351481. 65. ^ Milsom I, Abrams P, Cardozo L, Roberts RG, Thüroff J, Wein AJ (June 2001). "How widespread are the symptoms of an overactive bladder and how are they managed? A population-based prevalence study". BJU International. 87 (9): 760–6. doi:10.1046/j.1464-410x.2001.02228.x. PMID 11412210. 66. ^ Graham J (July 29, 2014). "An 'Emotional Burden' Rarely Discussed". New York Times. Retrieved August 23, 2014. 67. ^ Stothers L, Thom D, Calhoun E (2007). "Chapter 6: Urinary Incontinence in Men". Urologic Diseases in America Report. National Institutes of Health. 68. ^ Franco, Israel; Austin, Paul F; Bauer, Stuart B; von Gontard, Alexander; Homsy, Yves, eds. (2015). Pediatric incontinence - Franco - 2015 - Wiley Online Books - Wiley Online Library. doi:10.1002/9781118814789. ISBN 9781118814789. 69. ^ Becker H, Stenzl A, Wallwiener D, Zittel TT (2005). Urinary and fecal incontinence : an interdisciplinary approach; with 89 tables. Berlin [u.a.]: Springer. p. 232. ISBN 978-3540222255. 70. ^ O'Reilly T (8 June 2017). "Now Splinter Free: How Marketing Broke Taboos". CBC Radio One. Pirate Radio. Retrieved 10 June 2017. ## External links[edit] Classification D * ICD-10: N39.3-N39.4, R32 * ICD-9-CM: 788.3 * MeSH: D014549 * DiseasesDB: 6764 External resources * MedlinePlus: 003142 * eMedicine: med/2781 * Patient UK: Urinary incontinence * Urinary incontinence at Curlie * Patient-centered information from the European Urological Association * v * t * e Symptoms and signs relating to the urinary system Pain * Dysuria * Renal colic * Costovertebral angle tenderness * Vesical tenesmus Control * Urinary incontinence * Enuresis * Diurnal enuresis * Giggling * Nocturnal enuresis * Post-void dribbling * Stress * Urge * Overflow * Urinary retention Volume * Oliguria * Anuria * Polyuria Other * Lower urinary tract symptoms * Nocturia * urgency * frequency * Extravasation of urine * Uremia Eponymous * Addis count * Brewer infarcts * Lloyd's sign * Mathe's sign * v * t * e Diseases of the urinary tract Ureter * Ureteritis * Ureterocele * Megaureter Bladder * Cystitis * Interstitial cystitis * Hunner's ulcer * Trigonitis * Hemorrhagic cystitis * Neurogenic bladder dysfunction * Bladder sphincter dyssynergia * Vesicointestinal fistula * Vesicoureteral reflux Urethra * Urethritis * Non-gonococcal urethritis * Urethral syndrome * Urethral stricture * Meatal stenosis * Urethral caruncle Any/all * Obstructive uropathy * Urinary tract infection * Retroperitoneal fibrosis * Urolithiasis * Bladder stone * Kidney stone * Renal colic * Malakoplakia * Urinary incontinence * Stress * Urge * Overflow [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Urinary incontinence	c0042024	29,146	wikipedia	https://en.wikipedia.org/wiki/Urinary_incontinence	2021-01-18T18:32:11	{"mesh": ["D014549"], "umls": ["C0042024"], "icd-9": ["788.3"], "icd-10": ["R32", "N39.4", "N39.3"], "wikidata": ["Q281490"]}
Cutaneous small-vessel vasculitis Other namesHypersensitivity vasculitis, allergic vasculitis Example of hypersensitivity vasculitis Cutaneous small-vessel vasculitis (CSVV), also known as hypersensitivity vasculitis, cutaneous leukocytoclastic vasculitis, hypersensitivity angiitis, cutaneous leukocytoclastic angiitis, cutaneous necrotizing vasculitis and cutaneous necrotizing venulitis,[1] is inflammation of small blood vessels (usually post-capillary venules in the dermis), characterized by palpable purpura.[2]:831[3] It is the most common vasculitis seen in clinical practice. "Leukocytoclastic" refers to the damage caused by nuclear debris from infiltrating neutrophils in and around the vessels.[4] ## Contents * 1 Signs and symptoms * 1.1 Skin lesions * 1.2 Associated symptoms * 2 Cause * 3 Diagnosis * 3.1 Classification * 4 Treatment * 5 Additional images * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] ### Skin lesions[edit] Initially red to pink, flat spots (formally, "macules") and raised bumps (formally, "papules") may be seen on the skin.[5][6] Once fully developed, the classic appearance is "non-blanching, palpable purpura".[6][5] [7]This appears as deep red to purple spots that feel raised to the touch. Purpura refers to the red-purple discolored spots, while palpable implies that these spots can be felt as raised from the surrounding skin. Additionally, when gently pressed, the color does not fade to a lighter color ("non-blanching"). The red-purple color of the lesions is due to the inflammation in the blood vessels causing red blood cells to escape into the dermis skin layer.[6] Small fluid-filled blisters (or "vesicles"), pus-filled bumps resembling a pimple (or "pustules"), or shallow ulcers may also develop but are less common.[6][5] The location of skin lesions varies but are most commonly found symmetrically below the waist, primarily on the buttocks and legs. Other distributions include localized areas on the upper body or over several areas of the body.[6][5][8] With treatment, the lesions typically resolve in weeks to months and leave behind flat spots that are darker than the surrounding skin.[5] (see "Postinflammatory hyperpigmentation" on "Hyperpigmentation") A portion of cases may be persistent or recurrent. This tends to occur when the vasculitis is associated with chronic conditions such as connective tissue diseases.[5][8] ### Associated symptoms[edit] In most cases skin lesions do not cause symptoms, however itching, burning, or pain may occur.[5] Frequently reported symptoms include mild fever, muscle pain, joint pain, or an overall feeling of discomfort.[6][8] Additional symptoms depend on the cause of the vasculitis and if other organ systems are involved. For example, if the vasculitis is a manifestation of Henoch-Schönlein purpura, individuals may also experience abdominal pain or blood in the urine.[5] ## Cause[edit] Cutaneous vasculitis can have various causes including but not limited to medications, bacterial and viral infections or allergens. It is estimated that 45-55% of cases are idiopathic, meaning the cause is unknown.[5] In cases where a cause can be determined, medications and infectious pathogens are most common in adults, while IgA vasculitis (Henoch-Schönlein purpura) frequently affects children.[6] Other etiologies include autoimmune conditions and malignancies, usually hematologic (related to the blood).[5][6] Most Common Etiologies in Adults[5][6] Cause Frequency Examples Idiopathic 45-55% Cause unknown Infection 15-20% Staphylococcus and Streptococcus spp. Autoimmune 15-20% Rheumatoid arthritis, Systemic lupus erythematosus Medications 10-15% Antibiotics, Nonsteroidal anti-inflammatory drugs (NSAIDs) The small vessels in the skin affected are located in the superficial dermis and include arterioles (small arteries carrying blood to capillaries), capillaries, and venules (small veins receiving blood from capillaries).[5] In general, immune complexes deposit in vessel walls leading to activation of the complement system. C3a and C5a, proteins produced from the complement system, attract neutrophils to the vessels.[9] Once activated, neutrophils then release preformed substances, including enzymes causing damage to vessel tissue.[9] Evidence of this process can be seen with a sample of removed skin tissue, or biopsy, viewed under a microscope. Neutrophils are seen surrounding blood vessels and their debris within vessel walls, causing fibrinoid necrosis. This finding on histological examination is termed “leukocytoclastic vasculitis”.[5] Considering the wide range of potential causes leading to cutaneous small vessel vasculitis, there are subtle variations in the underlying pathophysiology for each cause. For example, medications are metabolized to smaller molecules that can attach to proteins in the blood or vessel walls.[10] The immune system senses these altered proteins as foreign and produces antibodies in efforts to eliminate them from the body. A similar process occurs with infectious agents, such as bacteria, in which antibodies target microbial components.[10] ## Diagnosis[edit] Micrograph of cutaneous small-vessel vasculitis. The section shows all features of leucocytoclastic vasculitis. A mixed inflammatory cell population surrounding the postcapillary venules of the superficial dermis. The infiltrate consists of neutrophils with nuclear dust (dashed arrows) and shows high affinity for the vessels. Features of vascular injury are shown including fibrinoid necrosis (asterisks) and erytrocyt extravasation (solid arrows).[11] The diagnostic testing for vasculitis should be guided by the patient's history and physical exam. The clinician should ask about the duration, onset, and presence any associated symptoms such as weight loss or fatigue (that would indicate a systemic cause).[12] It is important to distinguish between IgA and non-IgA vasculitis. IgA vasculitis is more likely to present with abdominal pain, bloody urine, and joint pain.[13] In the case that the cause is not obvious, a reasonable initial workup would include a complete blood count, urinalysis, basic metabolic panel, fecal occult blood testing, erythrocyte sedimentation rate (ESR), and C-reactive protein level.[13] Small vessel cutaneous vasculitis is a diagnosis of exclusion and requires ruling out systemic causes of the skin findings.[14] Skin biopsy (punch or excisional) is the most definitive diagnostic test and should be performed with 48 hours of appearance of the vasculitis.[6] A skin biopsy will be able to determine if the clinical findings are truly due to a vasculitis or due to some other cause.[15] ### Classification[edit] Subtypes of small-vessel vasculitis include:[2]:833–6 * IgA vasculitis (Henoch-Schönlein purpura)[16] * Acute hemorrhagic edema of infancy * Urticarial vasculitis * Cryoglobulinemic vasculitis * Erythema elevatum diutinum * Granuloma faciale * ANCA-associated vasculitis[13] * Arthropod bites[13] * Platelet dysfunction or deficiency[13] * Cholesterol emboli[13] * Septic emboli[13] * Livedoid vasculopathy[13] ## Treatment[edit] Treatment should be directed towards the specific underlying cause of the vasculitis. If no underlying cause is found and the vasculitis is truly limited to the skin then treatment is primarily supportive.[13] Such treatment involves measures such as leg elevation, stockings, and topical steroids to relieve itching/burning. If the vasculitis does not self-resolve within 3–4 weeks, more aggressive treatment may be warranted.[13] Oral colchicine or dapsone are often used for this purpose. If rapid control of symptoms is needed, a short course of high-dose oral steroids may be given.[12] Immunosuppressive agents such as methotrexate and azathioprine may be used in truly refractory cases not responsive to colchicine or dapsone.[17] ## Additional images[edit] * * * * ## See also[edit] * Skin lesion * List of cutaneous conditions ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 2. ^ a b 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. ^ Lotti T, Ghersetich I, Comacchi C, Jorizzo JL (November 1998). "Cutaneous small-vessel vasculitis". J. Am. Acad. Dermatol. 39 (5 Pt 1): 667–87, quiz 688–90. doi:10.1016/S0190-9622(98)70039-8. PMID 9810883. 4. ^ Harrison's Principles of Internal Medicine. 18th edition. Page 2798. 5. ^ a b c d e f g h i j k l m Bolognia, Jean L.; Schaffer, Julie V.; Duncan, Karynne O.; Ko, Christine J. (2014-02-26). Dermatology essentials. Bolognia, Jean,, Schaffer, Julie V.,, Duncan, Karynne O.,, Ko, Christine J. Oxford. ISBN 9780702055393. OCLC 877821912. 6. ^ a b c d e f g h i j Callen, Jeffrey P.; Jorizzo, Joseph L.; Zone, John J.; Piette, Warren; Rosenbach, Misha A.; Vleugels, Ruth Ann (2016-03-08). Dermatological signs of systemic disease. Callen, Jeffrey P., 1947- (Fifth ed.). Edinburgh. ISBN 9780323358316. OCLC 947111367. 7. ^ Upadhyay, AnimeshA; Kaushik, ShivaniB; Routt, Ethan; Phelps, Robert (2019). "Pustular vasculitis: Different names for same entity?". Indian Dermatology Online Journal. 0 (6): 721–723. doi:10.4103/idoj.idoj_415_18. ISSN 2229-5178. PMC 6859773. PMID 31807459. 8. ^ a b c Dermatopathology. Busam, Klaus J. (1st ed.). [Philadelphia]: Saunders/Elsevier. 2010. ISBN 9780443066542. OCLC 658000389.CS1 maint: others (link) 9. ^ a b K., Abbas, Abul (2015-11-02). Basic immunology : functions and disorders of the immune system. Lichtman, Andrew H.,, Pillai, Shiv,, Baker, David L. (Medical illustrator),, Baker, Alexandra (Fifth ed.). St. Louis, Mo. ISBN 9780323390828. OCLC 929898069. 10. ^ a b Kumar, Vinay; Abbas, Abul K.; Aster, Jon C. (2014). Robbins and Cotran pathologic basis of disease. Kumar, Vinay, 1944-, Abbas, Abul K.,, Aster, Jon C.,, Perkins, James A. (Ninth ed.). Philadelphia, PA. ISBN 9781455726134. OCLC 879416939. 11. ^ Giang, Jenny; Seelen, Marc A. J.; van Doorn, Martijn B. A.; Rissmann, Robert; Prens, Errol P.; Damman, Jeffrey (2018). "Complement Activation in Inflammatory Skin Diseases". Frontiers in Immunology. 9: 639. doi:10.3389/fimmu.2018.00639. ISSN 1664-3224. PMC 5911619. PMID 29713318. 12. ^ a b Dermatology. Bolognia, Jean., Jorizzo, Joseph L., Schaffer, Julie V. (3rd ed.). [Philadelphia]: Elsevier Saunders. 2012. ISBN 9780723435716. OCLC 802040381.CS1 maint: others (link) 13. ^ a b c d e f g h i j Small Vessel Vasculitis of the Skin, Rheumatic Disease Clinics of North America, 2015-02-01, Volume 41, Issue 1, Pages 21-32 14. ^ Emergency medicine : clinical essentials. Adams, James, 1962- (2nd ed.). Philadelphia, Pa: Elsevier/ Saunders. 2013. ISBN 9781455733941. OCLC 820203833.CS1 maint: others (link) 15. ^ L., BOLOGNIA, JEAN (2017). DERMATOLOGY. [S.l.]: ELSEVIER. ISBN 9780702062759. OCLC 981985926. 16. ^ J. C. Jennette; R. J. Falk; P. A. Bacon; et al. (January 2013). "2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides". Arthritis & Rheumatism. 65 (1): 1–11. doi:10.1002/art.37715. PMID 23045170. S2CID 20891451. 17. ^ 1950-, James, William D. (William Daniel) (2015-04-20). Andrews' diseases of the skin : clinical dermatology. Berger, Timothy G.,, Elston, Dirk M.,, Andrews, George Clinton, 1891-1978. (Twelfth ed.). Philadelphia, PA. ISBN 9780323319676. OCLC 910882314.CS1 maint: numeric names: authors list (link) ## External links[edit] Classification D * ICD-10: M31.0 External resources * Orphanet: 889 * v * t * e Cutaneous vasculitis and other vascular-related cutaneous conditions Cutaneous vasculitis * Erythema elevatum diutinum * Capillaritis * Urticarial vasculitis * Nodular vasculitis Microvascular occlusion * Calciphylaxis * Cryoglobulinemic purpura/Cryoglobulinemic vasculitis * vascular coagulopathy: Livedoid vasculitis * Livedoid dermatitis * Perinatal gangrene of the buttock * Malignant atrophic papulosis * Sneddon's syndrome Purpura * Nonthrombocytopenic purpura: Cryofibrinogenemic purpura * Drug-induced purpura * Food-induced purpura * IgA vasculitis * Obstructive purpura * Orthostatic purpura * Purpura fulminans * Purpura secondary to clotting disorders * Purpuric agave dermatitis * Pigmentary purpuric eruptions * Solar purpura * Traumatic purpura * Waldenström hyperglobulinemic purpura * Painful bruising syndrome * ungrouped: Paroxysmal hand hematoma * Postcardiotomy syndrome * Deep vein thrombosis * Superficial thrombophlebitis * Mondor's disease * Blueberry muffin baby * Fibrinolysis syndrome Systemic vasculitis * see Template:Systemic vasculitis Vascular malformations * Arteriovenous malformation * Bonnet–Dechaume–Blanc syndrome * Cobb syndrome * Parkes Weber syndrome * Sinusoidal hemangioma * lymphatic malformation * Hennekam syndrome * Aagenaes syndrome * telangiectasia: Generalized essential telangiectasia * Hereditary hemorrhagic telangiectasia * Unilateral nevoid telangiectasia Ulcer * Venous ulcer * Arterial insufficiency ulcer * Hematopoietic ulcer * Neuropathic ulcer * Acroangiodermatitis Lymphedema * see Template:Lymphatic vessel disease Ungrouped vascular-related cutaneous conditions * Raynaud's phenomenon * Thromboangiitis obliterans * Erythromelalgia * Septic thrombophlebitis * Arteriosclerosis obliterans * Bier spots/Marshall–White syndrome * Cholesterol embolus * Reactive angioendotheliomatosis * Trousseau's syndrome * v * t * e Systemic vasculitis Large vessel * Takayasu's arteritis * Giant cell arteritis Medium vessel * Polyarteritis nodosa * Kawasaki disease * Thromboangiitis obliterans Small vessel Pauci-immune * c-ANCA * Granulomatosis with polyangiitis * p-ANCA * Eosinophilic granulomatosis with polyangiitis * Microscopic polyangiitis Type III hypersensitivity * Cutaneous small-vessel vasculitis * IgA vasculitis Ungrouped * Acute hemorrhagic edema of infancy * Cryoglobulinemic vasculitis * Bullous small vessel vasculitis * Cutaneous small-vessel vasculitis Other * Goodpasture syndrome * Sneddon's 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Cutaneous small-vessel vasculitis	c0151436	29,147	wikipedia	https://en.wikipedia.org/wiki/Cutaneous_small-vessel_vasculitis	2021-01-18T19:06:19	{"gard": ["7851"], "mesh": ["D018366"], "umls": ["C4049638", "C0151436"], "orphanet": ["889"], "wikidata": ["Q1613670"]}
Wolf-Hirschhorn syndrome (WHS) is a genetic disorder that affects many parts of the body. The major features include a characteristic facial appearance, delayed growth and development, intellectual disability, low muscle tone (hypotonia), and seizures. Other features may include skeletal abnormalities, congenital heart defects, hearing loss, urinary tract malformations, and/or structural brain abnormalities. WHS is caused by a missing piece (deletion) of genetic material near the end of the short (p) arm of chromosome 4 (written as 4p-). The size of the deletion varies among people with WHS, and studies suggest larger deletions tend to result in more severe features. Most cases of WHS are not inherited, but some cases are inherited from a parent who does not have WHS. Treatment depends on the symptoms. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Wolf-Hirschhorn syndrome	c1956097	29,148	gard	https://rarediseases.info.nih.gov/diseases/7896/wolf-hirschhorn-syndrome	2021-01-18T17:57:05	{"mesh": ["D054877"], "omim": ["194190"], "umls": ["C1956097"], "orphanet": ["280"], "synonyms": ["WHS", "Wolf syndrome", "Chromosome 4p syndrome", "Microcephaly, IUGR, Hypertelorism, Ptosis, iris coloboma, hooked nose, external ear dysplasia, psychomotor retardation", "4p syndrome", "Distal deletion 4p", "4p- syndrome", "Distal monosomy 4p", "Telomeric deletion 4p", "Wittwer syndrome", "Pitt-Rogers-Danks syndrome"]}
Pediatric acute-onset neuropsychiatric syndrome (PANS) is a condition defined by sudden onset of obsessive-compulsive symptoms and/or severe eating restrictions, along with at least two other cognitive, behavioral, or neurological symptoms. Examples of other symptoms include anxiety, depression, tics, personality changes, decline in school performance, and sensory sensitivities. Symptoms typically begin during childhood but may begin at any age. Symptoms may go away for a while and then come back (referred to as a relapsing and remitting course). However, symptoms may be worse and last longer with each episode. PANS is thought to have a variety of possible causes. In more than 80% of cases, there is evidence of an abnormal autoimmune or inflammatory response in the brain following any of various infections in the body. When the associated infection is known to be strep, the condition is called PANDAS (a subtype of PANS). Other possible causes of PANS include psychological trauma and underlying autoimmune, neurological, endocrine, or metabolic disorders. There are likely non-infectious triggers that have not yet been identified. The diagnosis of PANS is made only when all other possible causes of symptoms are ruled out (this is a called a diagnosis of exclusion). Depending on the symptoms present, this process may rely on factors such as medical and psychiatric history, a physical exam, evaluation by various specialists, and a variety of tests or imaging studies such as blood tests, an electroencephalogram (EEG), sleep study (polysomnography) and/or brain MRI. Treatment depends on the symptoms and severity in each person and may involve improving symptoms with psychiatric medicines and behavioral interventions, treating underlying infections or sources of inflammation with antibiotics, and/or stabilizing the immune system with immunotherapy and/or anti-inflammatory therapies (in immune-related PANS). Treatment may be tapered down or stopped when symptoms resolve but may be needed again if symptoms return. Many people with PANS who undergo treatment show overall improvement over months to years or will recover completely. However, relapses may still occur after long periods of remission. Others will have ongoing symptoms that require continuous treatment. If not treated, PANS can lead to permanent debilitation. Unfortunately, at this time it is not possible to predict the course of the condition 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Pediatric acute-onset neuropsychiatric syndrome	None	29,149	gard	https://rarediseases.info.nih.gov/diseases/13087/pediatric-acute-onset-neuropsychiatric-syndrome	2021-01-18T17:58:24	{"synonyms": ["PANS"]}
A number sign (#) is used with this entry because of evidence that familial hypertrophic cardiomyopathy can be caused by heterozygous mutation in the NEXN gene (613121) on chromosome 1p31.1. For a phenotypic description and a discussion of genetic heterogeneity of familial hypertrophic cardiomyopathy, see CMH1 (192600). Clinical Features Wang et al. (2010) studied 2 Han Chinese families with hypertrophic cardiomyopathy (CMH). In the first family, the 37-year-old female proband had nonobstructive cardiac hypertrophy with an interventricular septal thickness of 21 mm and normal left ventricular systolic function, with T-wave changes on electrocardiogram (ECG). The proband's mother had died a sudden cardiac death at 38 years of age; the proband also had an affected brother and daughter, both of whom had asymmetric septal hypertrophy on echocardiogram, and the brother also had voltage criteria for left ventricular hypertrophy (LVH) on ECG. In the second family, the 45-year-old male proband had a left ventricular anterior wall thickness of 17 mm. His grandmother had died suddenly with suspected heart disease at 40 years of age, and his father and brother were also affected. His father had asymmetric left ventricular hypertrophy with an anterior wall thickness of 22 mm and atrial fibrillation and ST-T changes on ECG, and his younger brother had moderate asymmetric interventricular septal thickness (16 mm) and voltage criteria for LVH on ECG. Molecular Genetics Wang et al. (2010) analyzed the NEXN gene in 121 unrelated Han Chinese patients with CMH who were negative for mutations in 8 common myofilament-associated genes responsible for CMH, and they identified 2 heterozygous missense mutations in 2 probands (613121.0004 and 613121.0005, respectively) that segregated with disease in each family and were not found in 192 ethnically matched controls. INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Left ventricular hypertrophy \- Septal hypertrophy, asymmetric interventricular \- Left ventricular anterior wall hypertrophy (in some patients) \- Atrial fibrillation (in some patients) MOLECULAR BASIS \- Caused by mutation in the nexilin F-actin binding protein gene (NEXN, 613121.0004 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 20	c3151267	29,150	omim	https://www.omim.org/entry/613876	2019-09-22T15:57:14	{"omim": ["613876"], "genereviews": ["NBK1768"]}
## Clinical Features Jung et al. (1983) identified a familial immunodeficiency disease characterized by recurrent and persistent pyoderma, folliculitis, and atopic dermatitis. An affected father, aged 39 years, and his affected 11-year-old son were studied. The father's father, who had died, was alleged to have had a similar disease in childhood. Abnormalities of lymphocyte function (defective proliferative responses to phytomitogens and subnormal response in immunoglobulin production after stimulation of lymphocytes by pokeweed mitogen) and defective leukocyte chemiluminescence responses were associated with defective intracellular killing of microbial organisms. Chemotaxis was normal. The clinical manifestations and abnormalities of lymphocyte and leukocyte function responded dramatically to treatment with the histamine-1 antagonist, chlorpheniramine, suggesting to the authors a defect in histamine metabolism or abnormality of histamine receptors on lymphocytes and leukocytes. The son had corneal ulcerations; the father had had corneal transplants several times for scarring due to herpetic lesions. Jung et al. (1983) pointed out similarities to families reported by Van Scoy et al. (1975), Jacobs and Norman (1977), and Robinson et al. (1982). Jung et al. (1983) also noted that Mawhinney et al. (1980) had described a patient with hyper-IgE syndrome (147060), recurrent abscesses, and a chemotactic abnormality whose chemotactic defect and clinical disorder improved with treatment with cimetidine, an H2 blocker. Eyes \- Corneal ulcerations \- Corneal scarring Inheritance \- Autosomal dominant Immunology \- Immunodeficiency Lab \- Defective lymphocyte proliferative responses to phytomitogens \- Subnormal immunoglobulin production after stimulation of lymphocytes by pokeweed mitogen \- Defective leukocyte chemiluminescence responses \- Defective intracellular killing of microbial organisms \- Normal chemotaxis Skin \- Pyoderma \- Folliculitis \- Atopic dermatitis ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	IMMUNODEFICIENCY WITH DEFECTIVE LEUKOCYTE AND LYMPHOCYTE FUNCTION AND WITH RESPONSE TO HISTAMINE-1 ANTAGONIST	c1840265	29,151	omim	https://www.omim.org/entry/146840	2019-09-22T16:39:36	{"mesh": ["C564135"], "omim": ["146840"]}
Pontine tegmental cap dysplasia (PTCD) is a non-progressive neurological disorder characterized by significant developmental delay, cranial nerve dysfunction, and malformation of the hindbrain. Individuals with PTCD may have a collection of medical and developmental problems including: hearing impairment, ataxia, language and speech disorders, feeding and swallowing difficulties, heart malformations and facial paralysis. The severity of the medical problems varies among patients. Some patients have a good long-term prognosis with normal intelligence and partial speech. The cause of PTCD has not been identified. Treatment is focused on managing the underlying symptoms and may include interventions such as cochlear implantation. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Pontine tegmental cap dysplasia	c3541340	29,152	gard	https://rarediseases.info.nih.gov/diseases/10919/pontine-tegmental-cap-dysplasia	2021-01-18T17:58:15	{"omim": ["614688"], "orphanet": ["269229"], "synonyms": ["PTCD"]}
Abnormal state of wakefulness or altered state of consciousness For other uses, see Trance (disambiguation). This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Trance" – news · newspapers · books · scholar · JSTOR (August 2010) (Learn how and when to remove this template message) Dissociative trance The Oracle at Delphi was famous for her divinatory trances throughout the ancient Mediterranean world. Oil painting, John Collier, 1891 SpecialtyPsychiatry Trance is an abnormal state of wakefulness in which a person is not self-aware and is either altogether unresponsive to external stimuli (but nevertheless capable of pursuing and realizing an aim) or is selectively responsive in following the directions of the person (if any) who has induced the trance. Trance states may occur involuntarily and unbidden. The term trance may be associated[by whom?] with hypnosis, meditation, magic, flow, prayer, altered states of consciousness. ## Contents * 1 Etymology * 2 Working models * 3 Working definitions * 4 History * 4.1 Temple of Epidaurus: healing sleep * 4.2 Oracle at Delphi * 4.3 Oral lore and storytelling * 4.4 Military * 4.5 Mystics * 4.6 Christian mystics * 4.7 Mesmer and the origin of hypnotherapy * 4.8 Trance in American Christianity * 4.9 Trance and Anglo-American Protestants * 5 Trance induction and sensory modality * 5.1 Auditory driving and auditory art * 5.2 Visual driving and visual art * 5.3 Kinesthetic driving and somatic art * 6 Types and varieties * 7 Divination * 7.1 Nechung Oracle * 8 Scientific disciplines * 9 Brainwaves and brain rhythms * 10 See also * 11 Notes * 12 Further reading * 13 External links ## Etymology[edit] Trance in its modern meaning comes from an earlier meaning of "a dazed, half-conscious or insensible condition or state of fear", via the Old French transe "fear of evil", from the Latin transīre "to cross", "pass over".[1] ## Working models[edit] Wier, in his 1995 book, Trance: from magic to technology, defines a simple trance (p. 58) as a state of mind being caused by cognitive loops where a cognitive object (a thought, an image, a sound, an intentional action) repeats long enough to result in various sets of disabled cognitive functions. Wier represents all trances (which include sleep and watching television) as taking place on a dissociated trance plane where at least some cognitive functions such as volition are disabled; as is seen in what is typically termed a 'hypnotic trance'.[2] With this definition, meditation, hypnosis, addictions and charisma are seen as being trance states. In Wier's 2007 book, The Way of Trance, he elaborates on these forms, adds ecstasy as an additional form and discusses the ethical implications of his model, including magic and government use which he terms "trance abuse". John Horgan in Rational Mysticism (2003) explores the neurological mechanisms and psychological implications of trances and other mystical manifestations. Horgan incorporates literature and case-studies from a number of disciplines in this work: chemistry, physics, psychology, radiology and theology. ## Working definitions[edit] The following are some examples of trance states: * Enchantment: a psychological state induced by (or as if induced by) a magical incantation * A state of mind in which consciousness is fragile and voluntary action is poor or missing * A state resembling deep sleep * Capture: attract; cause to be enamored; "She/he captured all the men's hearts"; in the sense of entranced * A condition of apparent sleep or unconsciousness, with marked physiological characteristics, in which the body of the subject is thought by certain people to be liable to possession * An out-of-body experience in which one feels they have passed out of the body into another state of being, a rapture, an ecstasy. In a general way, the entranced conditions thus defined are divided into varying degrees of a negative, unconscious state, and into progressive gradations of a positive, conscious, illumining condition. * A state of hyper or enhanced suggestibility. * An induced or spontaneous sleep-like condition of an altered state of consciousness, which is thought by certain people to permit the subject's physical body to be utilized by disembodied spirits or entities as a means of expression * An altered state of awareness induced via hypnosis in which unconscious or dissociated responses to suggestion are enhanced in quality and increased in degree * A state induced by the use of hypnosis; the person accepts the suggestions of the hypnotist * A state of consciousness characterized by extreme dissociation often to the point of appearing unconscious. Trance conditions include all the different states of mind, emotions, moods and daydreams that human beings experience. All activities which engage a human involve the filtering of information coming into sense modalities, and this influences brain functioning and consciousness. Therefore, trance may be understood as a way for the mind to change the way it filters information in order to provide more efficient use of the mind's resources. Trance states may also be accessed or induced by various modalities and may be a way of accessing the unconscious mind for the purposes of relaxation, healing, intuition and inspiration. There is an extensive documented history of trance as evidenced by the case-studies of anthropologists and ethnologists and associated and derivative disciplines. Hence trance may be perceived as endemic to the human condition and a Human Universal. Principles of trance are being explored and documented as are methods of trance induction. Benefits of trance states are being explored by medical and scientific inquiry. Many traditions and rituals employ trance. Trance also has a function in religion and mystical experience. Castillo (1995) states that: "Trance phenomena result from the behavior of intense focusing of attention, which is the key psychological mechanism of trance induction. Adaptive responses, including institutionalized forms of trance, are 'tuned' into neural networks in the brain and depend to a large extent on the characteristics of culture. Culture-specific organizations exist in the structure of individual neurons and in the organizational formation of neural networks."[3] Hoffman (1998: p. 9) states that: "Trance is still conventionally defined as a state of reduced consciousness, or a somnolent state. However, the more recent anthropological definition, linking it to 'altered states of consciousness' (Charles Tart), is becoming increasingly accepted."[4] Hoffman (1998, p. 9) asserts that: "...the trance state should be discussed in the plural, because there is more than one altered state of consciousness significantly different from everyday consciousness."[4] ## History[edit] ### Temple of Epidaurus: healing sleep[edit] According to Hoffman (1998: p. 10), pilgrims visited the Temple of Epidaurus, an asclepeion, in Greece for healing sleep. Seekers of healing would make pilgrimage and be received by a priest who would welcome and bless them. This temple housed an ancient religious ritual promoting dreams in the seeker that endeavored to promote healing and the solutions to problems, as did the oracles. This temple was built in honor of Asclepios, the Greek god of medicine. The Greek treatment was referred to as incubation, and focused on prayers to Asclepios for healing. The asclepion at Epidaurus is both extensive and well-preserved, and is traditionally regarded as the birthplace of Asclepius. (For a comparable modern tool see Dreamwork.) ### Oracle at Delphi[edit] The Oracle at Delphi was also famous for trances in the ancient Greek world; priestesses there would make predictions about the future in exchange for gold.[5] ### Oral lore and storytelling[edit] Stories of the saints in the Middle Ages, myths, parables, fairy tales, oral lore and storytelling from different cultures are themselves potentially inducers of trance. Often literary devices such as repetition are employed which is evident in many forms of trance induction. Milton Erickson used stories to induce trance as do many NLP practitioners. ### Military[edit] From at least the 16th century it was held that march music may induce soldiers marching in unison into trance states where according to apologists, they bond together as a unit engendered by the rigors of training, the ties of comradeship and the chain of command. This had the effect of making the soldiers become automated, an effect which was widely evident in the 16th, 17th and 18th century due to the increasing prevalence of firearms employed in warcraft. Military instruments, especially the snare drum and other drums were used to entone a monotonous ostinato at the pace of march and heartbeat. High-pitched fifes, flutes and bagpipes were used for their "piercing" effect to play the melody. This would assist the morale and solidarity of soldiers as they marched to battle. Joseph Jordania recently proposed a term battle trance for this mental state, when combatants do not feel fear and pain, and when they lose their individual identity and acquire a collective identity.[6] The Norse Berserkers induced a trance-like state before battle, called Berserkergang. It is said to have given the warriors superhuman strength and made them impervious to pain during battle. This form of trance could have been induced partly due to ingestion of hallucinogenic mushrooms. ### Mystics[edit] As the mystical experience of mystics generally entails direct connection, communication and communion with Deity, Godhead and/or god; trance and cognate experience are endemic. (see Yoga, Sufism, Shaman, Umbanda, Crazy Horse, etc.) As shown by Jonathan Garb,[7] trance techniques also played a role in Lurianic Kabbalah, the mystical life of the circle of Moshe Hayyim Luzzatto and Hasidism. ### Christian mystics[edit] Many Christian mystics are documented as having experiences that may be considered as cognate with trance, such as: Hildegard of Bingen, John of the Cross, Meister Eckhart, Saint Theresa (as seen in the Bernini sculpture) and Francis of Assisi. ### Mesmer and the origin of hypnotherapy[edit] * Mesmer, an influential but discredited promoter of trance states and their curative powers. * Milton Erickson, the founder of hypnotherapy who died in 1980, introduced trance and hypnosis to orthodox medicine and psychotherapy—hypnosis here is something different from traditional clinical hypnosis. ### Trance in American Christianity[edit] Taves (1999) charts the synonymic language of trance in the American Christian traditions: power or presence or indwelling of God, or Christ, or the Spirit, or spirits. Typical expressions include "the indwelling of the Spirit" (Jonathan Edwards), "the witness of the Spirit" (John Wesley), "the power of God" (early American Methodists), being "filled with the Spirit of the Lord" (early Adventists; see charismatic Adventism), "communing with spirits" (Spiritualists), "the Christ within" (New Thought), "streams of holy fire and power" (Methodist holiness), "a religion of the Spirit and Power" (the Emmanuel Movement), and "the baptism of the Holy Spirit" (early Pentecostals). (Taves, 1999: 3) ### Trance and Anglo-American Protestants[edit] Taves (1999) well-referenced book on trance charts the experience of Anglo-American Protestants and those who left the Protestant movement beginning with the transatlantic awakening in the early 18th century and ending with the rise of the psychology of religion and the birth of Pentecostalism in the early 20th century. This book focuses on a class of seemingly involuntary acts alternately explained in religious and secular terminology. These involuntary experiences include uncontrolled bodily movements (fits, bodily exercises, falling as dead, catalepsy, convulsions); spontaneous vocalizations (crying out, shouting, speaking in tongues); unusual sensory experiences (trances, visions, voices, clairvoyance, out-of-body experiences); and alterations of consciousness and/or memory (dreams, somnium, somnambulism, mesmeric trance, mediumistic trance, hypnosis, possession, alternating personality) (Taves, 1999: 3). ## Trance induction and sensory modality[edit] Trance-like states are often interpreted as religious ecstasy or visions and can be deliberately induced using a variety of techniques, including prayer, religious rituals, meditation, pranayama (breathwork or breathing exercises), physical exercise, sexual intercourse, music, dancing, sweating (e.g. sweat lodge), fasting, thirsting, and the consumption of psychotropic drugs such as cannabis. Sensory modality is the channel or conduit for the induction of the trance. Sometimes an ecstatic experience takes place in occasion of contact with something or somebody perceived as extremely beautiful or holy. It may also happen without any known reason. The particular technique that an individual uses to induce ecstasy is usually one that is associated with that individual's particular religious and cultural traditions. As a result, an ecstatic experience is usually interpreted within the context of a particular individual's religious and cultural traditions. These interpretations often include statements about contact with supernatural or spiritual beings, about receiving new information as a revelation, also religion-related explanations of subsequent change of values, attitudes and behavior (e.g. in case of religious conversion). Benevolent, neutral and malevolent trances may be induced (intentionally, spontaneously and/or accidentally) by different methods: * Auditory: driving through the sense of hearing by chanting, auditory story telling, mantra, overtone singing, drumming, music, etc.;, * Kinesthetic: driving through the sense of feeling and movement through the kinesphere by ecstatic dance, story telling by movement, mudra, embodying rituals, yoga, breathwork, oxygen deprivation, sexual stimulation etc.; * Visual: driving through the sense of sight by yantra, visual story telling, mandala, cinema, theater, art, architecture, beauty, strobe lights, form constants, symmetry; * Olfactory: driving via scent through the sense of smell by perfume, pheromones, incense, flowers, pollen, indeed any scent for which we have an association or memory, etc.; * Gustatory: driving through the sense of taste and indigestion; including: starvation, herbs, hallucinogens and drugs. As the intake of food and beverage entails intra-bodily chemical reactions through digestion, some infer that all food may be considered medicine or drugs and therefore contribute to the induction of discernible psycho-physical states (see Ancient Medicine). Trance states can be attained through the ingestion of psychoactive drugs, particularly psychedelics, such as cannabis, ketamine, LSD, peyote, psilocybin mushrooms, DMT, and MDMA. * Disciplines: Yoga, Sufism, Surat Shabd Yoga; meditation; * Miscellaneously: traumatic accident, sleep deprivation, nitrogen narcosis (deep diving), fever, by the use of a sensory deprivation tank or mind-control techniques, hypnosis, meditation, prayer; * Naturally occurring: dreams, lucid dreams, euphoria, ecstasy, psychosis as well as purported premonitions, out-of-body experiences, and channeling. ### Auditory driving and auditory art[edit] Charles Tart provides a useful working definition of auditory driving. It is the induction of trance through the sense of hearing. Auditory driving works through a process known as entrainment.[citation needed] The usage of repetitive rhythms to induce trance states is an ancient phenomenon. Throughout the world, shamanistic practitioners have been employing this method for millennia. Anthropologists and other researchers have documented the similarity of shamanistic auditory driving rituals among different cultures. Said simply, entrainment is the synchronization of different rhythmic cycles. Breathing and heart rate have been shown to be affected by auditory stimulus, along with brainwave activity. The ability of rhythmic sound to affect human brainwave activity, especially theta brainwaves, is the essence of auditory driving, and is the cause of the altered states of consciousness that it can induce.[citation needed] ### Visual driving and visual art[edit] Nowack and Feltman have recently published an article entitled "Eliciting the Photic Driving Response" which states that the EEG photic driving response is a sensitive neurophysiological measure which has been employed to assess chemical and drug effects, forms of epilepsy, neurological status of Alzheimer's patients, and physiological arousal. Photic driving also impacts upon the psychological climate of a person by producing increased visual imagery and decreased physiological and subjective arousal. In this research by Nowack and Feltman, all participants reported increased visual imagery during photic driving, as measured by their responses to an imagery questionnaire. Dennis Wier (https://web.archive.org/web/20060915232957/http://www.trance.edu/papers/theory.htm Accessed: 6 December 2006) states that over two millennia ago Ptolemy and Apuleius found that differing rates of flickering lights affected states of awareness and sometimes induced epilepsy. Wier also asserts that it was discovered in the late 1920s that when light was shined on closed eyelids it resulted in an echoing production of brainwave frequencies. Wier also opined that in 1965 Grey employed a stroboscope to project rhythmic light flashes into the eyes at a rate of 10–25 Hz (cycles per second). Grey discovered that this stimulated similar brainwave activity. Research by Thomas Budzynski, Oestrander et al., in the use of brain machines suggest that photic driving via the suprachiasmatic nucleus and direct electrical stimulation and driving via other mechanisms and modalities, may entrain processes of the brain facilitating rapid and enhanced learning, produce deep relaxation, euphoria, an increase in creativity, problem solving propensity and may be associated with enhanced concentration and accelerated learning. The theta range and the border area between alpha and theta has generated considerable research interest. ### Kinesthetic driving and somatic art[edit] Charles Tart provides a useful working definition of kinesthetic driving. It is the induction of trance through the sense of touch, feeling or emotions. Kinesthetic driving works through a process known as entrainment. The rituals practiced by some athletes in preparing for contests are dismissed as superstition, but this is a device of sport psychologists to help them to attain an ecstasy-like state. Joseph Campbell had a peak experience whilst running. Roger Bannister on breaking the four-minute mile (Cameron, 1993: 185): "No longer conscious of my movement, I discovered a new unity with nature. I had found a new source of power and beauty, a source I never dreamt existed." Roger Bannister later became a distinguished neurologist. Mechanisms and disciplines that include kinesthetic driving may include: dancing, walking meditation, yoga and asana, mudra, juggling, poi (juggling), etc. Sufism (the mystical branch of Islam) has theoretical and metaphoric texts regarding ecstasy as a state of connection with Allah. Sufi practice rituals (dhikr, sema) use body movement and music to achieve the state. ## Types and varieties[edit] * Maenads and Bacchae: in Greek mythology, Maenads were female worshippers of Dionysus, the Greek god of mystery, wine and intoxication, and the Roman god Bacchus. The word literally translates as "raving ones". They were known as wild, insane women who could not be reasoned with. The mysteries of Dionysus inspired the women to ecstatic frenzy; they indulged in copious amounts of violence, bloodletting, sexual activity, self-intoxication, and mutilation. They were usually pictured as crowned with vine leaves, clothed in fawnskins and carrying the thyrsus, and dancing with wild abandon. They were also characterized as entranced women, wandering through the forests and hills.[8] The Maenads were also known as Bassarids (or Bacchae or Bacchantes) in Roman mythology, after the penchant of the equivalent Roman god, Bacchus, to wear a fox-skin, a bassaris. * Norse berserkers were said to have often entered battle entrenched in a state of primal rage, biting their shields and howling like wolves. This fanaticism was so powerful that they were known to continue fighting even after having lost limbs or being otherwise deeply wounded. * Samādhi: yoga provides techniques to attain a state of ecstasy called samādhi. According to practitioners, there are various stages of ecstasy, the highest of which is called Nirvikalpa samādhi. Different traditions have different understanding of Samādhi.[9] * Bhakti: (Devanāgarī: भक्ति) is a word of Sanskrit origin meaning "devotion" and also "the path of devotion" itself, as in Bhakti-yoga. Within Hinduism the word is used exclusively to denote devotion to a particular deity or form of God. Within Vaishnavism bhakti is only used in conjunction with Vishnu or one of his associated incarnations, it is likewise used towards Shiva by followers of Shaivism. Saints in these traditions exhibit different trance states or ecstasy. * Agape or "Divine Love": the term agape appears in the Odyssey twice, where the word describes something that creates contentedness within the speaker. * Communion: In the monotheistic tradition, religious ecstasy is usually associated with communion and oneness with God. Indeed, ecstasy is the primary vehicle for the type of prophetic visions and revelations found in the Bible. However, such experiences can also be personal mystical experiences with no significance to anyone but the person experiencing them. * Rapture or religious ecstasy: is an altered state of consciousness characterized by greatly reduced external awareness and expanded interior mental and spiritual awareness which is frequently accompanied by visions and emotional/intuitive (and sometimes physical) euphoria. Although the experience is usually brief in physical time, there are records of such experiences lasting several days or even more, and of recurring experiences of ecstasy during one's lifetime. Subjective perception of time, space and/or self may strongly change or disappear during ecstasy. * Peak experiences: is a term developed by Abraham Maslow and used to describe certain extra-personal and ecstatic states, particularly ones tinged with themes of unification, harmonization and interconnectedness. Participants characterize these experiences, and the revelations imparted therein, as possessing an ineffably mystical (or overtly religious) quality or essence. * In Christianity, the ecstatic experiences of the Apostles Peter and Paul are recorded in Acts 10:10, 11:5 and 22:17. * Some charismatic Christians practice ecstatic states (called, e.g., "being slain in the Spirit") and interpret these as given by the Holy Spirit. * In hagiography (writings on the subject of Christian saints) many instances are recorded in which saints are granted ecstasies. According to the Catholic Encyclopedia,[10] religious ecstasy (called supernatural ecstasy) includes two elements: one, interior and invisible, in which the mind rivets its attention on a religious subject, and another, corporeal and visible, in which the activity of the senses is suspended, reducing the effect of external sensations upon the subject and rendering him or her resistant to awakening. * Trance states have also long been used by shamans, mystics, and fakirs in healing rituals, being particularly cultivated in some religions, such as Tibetan Buddhism. Australian shamanism has been observed[11][12] ## Divination[edit] Divination is a cultural universal which anthropologists have observed as being present in many religions and cultures in all ages up to the present day (see sibyl).[citation needed] Divination may be defined as a mechanism for fortune-telling by ascertaining information by interpretation of omens or an alleged supernatural agency. Divination often entails ritual, and is often facilitated by trance. ### Nechung Oracle[edit] In Tibet, oracles have played, and continue to play, an important part in religion and government. The word oracle is used by Tibetans to refer to the spirit, deity or entity that enters those men and women who act as media between the natural and the spiritual realms. The media are, therefore, known as kuten, which literally means, "the physical basis". The Dalai Lama, who lives in exile in northern India, still consults an oracle known as the Nechung Oracle, which is considered the official state oracle of the government of Tibet. He gives a complete description of the process of trance and possession in his book Freedom in Exile.[13] ## Scientific disciplines[edit] Convergent disciplines of neuroanthropology, ethnomusicology, electroencephalography (EEG), neurotheology and cognitive neuroscience, amongst others, are conducting research into the trance induction of altered states of consciousness resulting from neuron entrainment with the driving of sensory modalities, for example polyharmonics, multiphonics, and percussive polyrhythms through the channel of the auditory and kinesthetic modality. Neuroanthropology and cognitive neuroscience are conducting research into the trance induction of altered states of consciousness (possibly engendering higher consciousness) resulting from neuron firing entrainment with these polyharmonics and multiphonics. Related research has been conducted into neural entraining with percussive polyrhythms. The timbre of traditional singing bowls and their polyrhythms and multiphonics are considered meditative and calming, and the harmony inducing effects of this tool to potentially alter consciousness are being explored by scientists, medical professionals and therapists. ## Brainwaves and brain rhythms[edit] See also: Neural oscillation Scientific advancement and new technologies such as computerized EEG, positron emission tomography, regional cerebral blood flow, and nuclear magnetic resonance imaging, are providing measurable tools to assist in understanding trance phenomena. There are four principal brainwave states that range from high-amplitude, low-frequency delta to low-amplitude, high-frequency beta. These states range from deep dreamless sleep to a state of high arousal. These four brainwave states are common throughout humans. All levels of brainwaves exist in everyone at all times, even though one is foregrounded depending on the activity level. When a person is in an aroused state and exhibiting a beta brainwave pattern, their brain also exhibits a component of alpha, theta and delta, even though only a trace may be present.[14] The University of Philadelphia study on some Christians at the Freedom Valley Worship Center in Gettysburg, Pennsylvania, revealed that glossolalia-speaking (vocalizing or praying in unrecognizable form of language which is seen in members of certain Christian sects) activates areas of the brain out of voluntary control. In addition, the frontal lobe of the brain, which monitors speech, significantly diminished in activity as the study participants spoke glossolalia.[15] Dr. Andrew B. Newberg, in analysis of his earlier studies as opposed to the MRI scans of the test subjects, stated that Buddhist monks in meditation[16] and Franciscan nuns in prayer[17] exhibited increased activity in the frontal lobe, and subsequently their behaviors, very much under voluntary control. The investigation found this particular beyond-body-control characteristic only in tongue-speakers (also see xenoglossia). ## See also[edit] * Autohypnosis * Candomblé * Contemplative education * Ecstasy (emotion) * Ecstasy (philosophy) * Edgar Cayce * Entheogen * Etat second * Gavari * Hallucinations in the sane * Henri Bergson * Hesychasm * Highway hypnosis * Huston Smith * Hypnagogia * Hypnosis * Immanence * Jesus Prayer * Mysticism * Nirvana * Ramakrishna * Religious experience * Rigpa * Satchitananda * Shamanism * Tangki * Temporal lobe epilepsy * Transcendence (philosophy) * Transcendence (religion) * Transpersonal psychology * Unio Mystica * Wajad ## Notes[edit] 1. ^ "Online Etymology Dictionary". Etymonline.com. Retrieved 7 November 2012. 2. ^ "Archived copy". Archived from the original on 8 December 2009. Retrieved 24 July 2009.CS1 maint: archived copy as title (link) 3. ^ Castillo, Richard J. (1995). Culture, Trance, and the Mind-Brain. In Anthropology of Consciousness. Volume 6, Number 1, March 1995, pp. 17–34. 4. ^ a b Hoffman, Kay (1998). The Trance Workbook: understanding & using the power of altered states. Translated by Elfie Homann, Clive Williams, and Dr Christliebe El Mogharbel. Translation edited by Laurel Ornitz. ISBN 0-8069-1765-2 p. 9 5. ^ Diodorus Siculus 16.26.1–4. 6. ^ Joseph Jordania, Why do People Sing? Music in Human Evolution. Logos, 2011 7. ^ (Shamanic Trance in Modern Kabbalah, 2011) 8. ^ Wiles, David (2000). Greek Theatre Performance: An Introduction. Cambridge University Press. Source: [1] 9. ^ Sarbacker, Stuart Ray (2012). Samadhi: The Numinous and Cessative in Indo-Tibetan Yoga. SUNY Press. p. 13. 10. ^ "CATHOLIC ENCYCLOPEDIA: Ecstasy". newadvent.org. 11. ^ Lawlor (1991: p. 374) states that: "The supernormal, super sensory powers of Aboriginal wise woman and men of high degree, by their own accounts, comes directly from initiations administered by the ancestral sky heroes themselves and by the totemic spirits. Those who have gone through these initiations alone, in a deep trance that makes them lose their personal identities and confront manifestations of the ancestral powers, are held in the highest regard." 12. ^ Lawlor (1991: p. 303) states that: "One such animal dance ceremony was observed and photographed by Gillen and Spencer. More than 30 naked men gathered in a large circle. One by one, each man performed the dance of the animal to be hunted while the others sang and slapped their buttocks to create a percussive beat for the dancer. The slapping sound was so loud that it could be heard for miles across the surrounding desert. The dance continued for hours, with each man dancing frenetically until he dropped from exhaustion. The eyes of the onlookers soon became glazed with entrancement; their penises were erect in a state of ecstatic arousal. Finally, after the last man had performed the animal dance and collapsed in exhaustion, the entire group leaped on him, emitting a loud abandoned cry. The next day the hunt began." 13. ^ "Archived copy". Archived from the original on 5 December 2006. Retrieved 23 January 2007.CS1 maint: archived copy as title (link) 14. ^ "What is the function of the various brainwaves?". Scientific American. Retrieved 4 April 2019. 15. ^ Newberg A, Wintering NA, Morgan D, Waldman MR. The measurement of regional cerebral blood flow during glossolalia: A preliminary SPECT study. Psychiatry Research: Neuroimaging 148(1):67–71, 2006. 16. ^ Newberg AB, Alavi A, Baime M, Pourdehnad M, Santanna J, d'Aquili EG. The measurement of regional cerebral blood flow during the complex cognitive task of meditation: A preliminary SPECT study. Psychiatry Research: Neuroimaging 106: 113–122, 2001. 17. ^ Newberg A, Pourdehnad M, Alavi A, d’Aquili E. Cerebral blood flow during meditative prayer: Preliminary findings and methodological issues. Perceptual and Motor Skills 97: 625–630, 2003. ## Further reading[edit] * Cameron, Julia (1993). The Artist's Way. Oxford, London: Pan Books. ISBN 0-330-34358-0 * Castillo, Richard J. (1995). Culture, Trance, and the Mind-Brain. In Anthropology of Consciousness. Volume 6, Number 1, March 1995, pp. 17–34.* Horgan, John (2003). Rational Mysticism: Dispatches from the Border Between Science and Spirituality. New York: Houghton Mifflin. * Goodman, Felicitas D. (1999). Ritual Body Postures, Channeling, and the Ecstatic Body Trance. In Anthropology of Consciousness. Volume 10, Number 1 (March 1999). * Heinze, Ruth-Inge (1994). Applications of Altered States of Consciousness in Daily Life. In Anthropology of Consciousness. Volume 5, Number 3, September 1994, pp. 8–12. * Hoffman, Kay (1998). The Trance Workbook: understanding & using the power of altered states. Translated by Elfie Homann, Clive Williams, and Dr Christliebe El Mogharbel. Translation edited by Laurel Ornitz. ISBN 0-8069-1765-2 * Hubbard, Timothy L. (2003). Some Correspondences and Similarities of Shamanism and Cognitive Science: Interconnectedness, Extension of Meaning, and Attribution of Mental States. In Anthropology of Consciousness. Volume 14, Number 1, March–June 2003, pp. 26–45 * Inglis, Brian (1990). Trance: A Natural History of Altered States of Mind. London, Paladin. ISBN 0-586-08933-0 * James, William The varieties of religious experience (1902) ISBN 0-14-039034-0 * Lawlor, Robert (1991). Voices of the First Day: Awakening in the Aboriginal dreamtime. Rochester, Vermont: Inner Traditions International, Ltd. ISBN 0-89281-355-5 * Lewis, I.M. (2003). Trance, Possession, Shamanism and Sex. In Anthropology of Consciousness. Volume 14, Number 1, March–June 2003, pp. 20–39. * McDaniel, June (1989). The Madness of the Saints: Ecstatic Religion in Bengal. University of Chicago Press. ISBN 0-226-55723-5 (Paper); 0-226-55722-7 (Cloth) & ISBN 978-0-226-55723-6 (Paper); 978-0-226-55722-9 (Cloth). * Michaelson, Jay (1997). "Paths to the Divine: Ecstatics and Theology in R. Dov Baer of Lubavitch" (6 December 2006) * Narr. Maybrey, Vicki. "Speaking in Tongues Medical Study proves Holy Spirit praying." Nightline. ABC. Gettysburg, Philadelphia, 17 July. 2008. * Neophytou, Charles (1996). The Encyclopedia of Mind Body and Spirit. Millennium Edition. Yanchep, Western Australia: Lindlahr Book Publishing. ISBN 0-646-26789-2 * Nowack, William J & Feltman, Mary L. (date?) "Eliciting the Photic Driving Response". American Journal of Electroneurodiagnostic Technology. Vol. 38, No. 1, pp. 43–45. * Rich, Grant Jewell (2001). Domestic Paths to Altered States and Transformations of Consciousness. Volume 12, Number 2 (September–December 2001). * Smith, Huston (2000). Cleansing the Doors of Perception: The Religious Significance of Entheogenic Plants and Chemicals. Tarcher/Putnam, ISBN 1-58542-034-4, Council on Spiritual Practices, ISBN 1-889725-03-X * Tart, Charles T., editor. Altered States of Consciousness (1969) ISBN 0-471-84560-4 * Tart, Charles T. States of Consciousness (2001) ISBN 0-595-15196-5 * Taves, Ann (1999). Fits, Trances, & Visions: Experiencing Religion and Explaining Experience from Wesley to James. Princeton, New Jersey: Princeton University Press. * Vitebsky, Piers, The Shaman: Voyages of the Soul – Trance, Ecstasy and Healing from Siberia to the Amazon, Duncan Baird, 2001. ISBN 1-903296-18-8 * Von Gizycki, H., Jean-Louis, G., Snyder, M., Zizi, F., Green, H., Giuliano, V., Spielman, A., Taub, H. (1998). "The effects of photic driving on mood states" in Journal of Psychosomatic Research. Vol. 44, N. 5, pp. 599–604. New York, NY: Elsevier. ISSN 0022-3999 * Vyner, Henry M. (2002). The Descriptive Mind Science of Tibetan Buddhist Psychology and the Nature of the Healthy Human Mind. In Anthropology of Consciousness. Volume 13, Number 2, September–December 2002, pp. 1–25. * Wallis, Robert (1999). Altered States, Conflicting Cultures: Shamans, Neo-Shamans and Academics. In Anthropology of Consciousness. Volume 10, Numbers 2–3 (June–September 1999). * Warren, Jeff (2007). "The Trance". The Head Trip: Adventures on the Wheel of Consciousness. Toronto: Random House Canada. ISBN 978-0-679-31408-0.* Wier, Dennis R. Trance: from magic to technology (1995) ISBN 1-888428-38-4 * Wier, Dennis R. (2007). The Way of Trance Laytonville, California: Trance Research Foundation. ISBN 978-1-888428-10-0. * Wilde, Stuart. (1996). The Art of Meditation. Carlsbad: Hay House. ISBN 978-1-56170-530-6 ## External links[edit] Classification D * ICD-10: F44.89 * ICD-9-CM: 300.15 Look up trance in Wiktionary, the free dictionary. Wikisource has the text of the 1911 Encyclopædia Britannica article Trance. Wikimedia Commons has media related to Trance. * HypnosisAndSuggestion.org Exploring the science behind hypnosis and suggestion * InduceTrance.com Induce Hypnotic Trance Naturally * "Trance State Meditation" Khris Krepcik, The Hooded Sage * The Emergence of Novel Information during Trance Authority control * BNE: XX5188793 * BNF: cb11933620g (data) * GND: 4130086-5 * LCCN: sh85136857 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Trance	c0855240	29,153	wikipedia	https://en.wikipedia.org/wiki/Trance	2021-01-18T18:49:17	{"umls": ["C0855240"], "icd-9": ["780.09"], "icd-10": ["F44.3"], "wikidata": ["Q466475"]}
A number sign (#) is used with this entry because chylomicron retention disease (CMRD), also referred to as Anderson disease, is caused by homozygous or compound heterozygous mutation in the SAR1B gene (607690) on chromosome 5q31. Description Chylomicron retention disease is an autosomal recessive disorder of severe fat malabsorption associated with failure to thrive in infancy (Dannoura et al., 1999). Clinical Features Anderson et al. (1961), Lamy et al. (1967) and Silverberg et al. (1968) described infants with severe steatorrhea. An intestinal defect in lipid transport and a failure of chylomicron formation was suggested, similar to that observed in abetalipoproteinemia (200100). However, neither acanthocytosis nor neuroocular symptoms occurred in Anderson disease. Bouma et al. (1986) described 7 cases (3 young adults and 4 children) in 5 kindreds with Anderson disease. Several of the patients were of Algerian descent. All presented with severe diarrhea in childhood and had a varying degree of growth retardation. The diagnosis was established by the finding of fat-laden enterocytes in small bowel biopsies. The transmission pattern was consistent with autosomal recessive inheritance. Enterocytes isolated from intestinal biopsies of patients after an overnight fast show numerous fat droplets, as in abetalipoproteinemia. Immunoenzymatic staining of enterocytes showed large amounts of material that reacted with a polyclonal antiserum to apolipoprotein B (107730) and a monoclonal antibody to B48. Roy et al. (1987) and Kane and Havel (1989) described chylomicron retention disease. Roy et al. (1987) reported 8 affected infants and distinguished the disorder from abetalipoproteinemia. One of the patients had mild acanthocytosis and 3 patients in their teens had mild peripheral neuropathy with diminished or absent deep tendon reflexes and diminished vibratory sense, and definite or borderline mental retardation. All showed severe growth retardation, steatorrhea, and malnutrition with hypoalbuminemia in 3 and undetectably low plasma vitamin E levels in 5. Although none had retinitis pigmentosa, some showed mild defects in color vision. Nemeth et al. (1995) described 2 sibs with fat malabsorption and jejunal chylomicron retention. Plasma lipoproteins were studied in the patients and their first-degree Relatives. The patients were a 14-year-old girl and her 8-year-old brother. Compared to healthy controls, they both had low fasting plasma concentrations of plasma total, HDL, and LDL cholesterol, as well as of apolipoproteins A-I (107680) and B. No increase in plasma lipoprotein levels or detectable apo B-48 was observed following an oral fat load. Histologic studies of jejunal biopsy specimens obtained during fasting and 1 hour postprandially showed severe steatosis, and an apparent block of chylomicron secretion from the endoplasmic reticulum into the Golgi apparatus was observed by electron microscopy. Liver biopsy specimens showed moderate steatosis and ultrastructural changes similar to those in the enterocytes. One healthy sister had a normal plasma lipoprotein pattern, and showed increased plasma triglyceride levels as well as the presence of apo B-48 following an oral fat load. Both parents had normal plasma total cholesterol levels, but clearly reduced fasting concentrations of HDL cholesterol and apo A-I. Nemeth et al. (1995) suggested that at least in this family, determination of plasma apo A-I levels might thus prove useful in the identification of heterozygotes. ### Clinical Variability Aguglia et al. (2000) described 2 Italian brothers, aged 19 and 12 years, who presented with a clinical diagnosis of Marinesco-Sjogren syndrome (MSS; 248800). They also had very low serum vitamin E concentrations and an absence of postprandial chylomicrons. Ataxia with isolated vitamin E deficiency (277460), abetalipoproteinemia, and hypobetalipoproteinemia (605019) were ruled out. Findings on electron microscopy of the intestinal mucosa were consistent with chylomicron retention disease. Aguglia et al. (2000) postulated that both CMRD and MSS were related to defects in a gene crucial for the assembly or secretion of chylomicron particles. In the brothers reported by Aguglia et al. (2000), Jones et al. (2003) identified a mutation in the SAR1B gene (607690.0006), responsible for CMRD, and Annesi et al. (2007) identified a mutation in the SIL1 gene (608005.0004), responsible for MSS. The findings indicated that the patients had 2 distinct diseases due to mutations in 2 different genes, rather than defects in a single gene leading to both disorders. Other Features Silvain et al. (2008) reported increased serum creatine kinase in 8 CMRD patients between the ages of 13 and 39 years. Two patients had mild clinical symptoms suggestive of mechanical muscle irritability, but none had frank muscle weakness. A 38-year-old woman had increased CK-MB, but no evidence of cardiac dysfunction. A 35-year-old woman had normal serum CK-MB, but decreased cardiac ejection fraction. Inheritance Lamy et al. (1967) reported 2 affected brothers, and Silverberg et al. (1968) noted parental consanguinity, both suggesting autosomal recessive inheritance. Pathogenesis By in vitro studies of small intestinal explants from CMRD patients, Levy et al. (1987) found normal apoB-48 protein synthesis, but deficient glycosylation. The authors postulated a defect in the formation and secretion of chylomicrons resulting from a defect in glycosylation. Dannoura et al. (1999) studied 8 patients with Anderson disease from 7 unrelated families of North African origin after treatment with a low-fat diet. Lipid loading of intestinal biopsies persisted, but the pattern and the extent of loading varied among the patients. Electron microscopy showed lipoprotein-like particles in membrane-bound compartments, the densities and mean diameters of which were, in general, significantly larger than in normal-fed subjects. There were also large lipid particles with diameters up to 7,043 nm that were not surrounded by a membrane. Rarely, lipoprotein-like particles were observed in the intercellular spaces. All of these changes could be seen in all patients. Intestinal organ cultures showed that apolipoprotein B and apolipoprotein A-IV (APOA4; 107690) were synthesized with apparently normal molecular masses and that small amounts were secreted in lipid-bound forms. Normal microsomal triglyceride transfer protein (MTP; 157147) and activity were also detected in intestinal biopsies. Segregation analyses of 4 families excluded involvement of significant regions of the genome surrounding the genes encoding the apolipoproteins expressed in the intestine, as well as the genes encoding 3 intracellular lipid transport proteins, MTP, FABP1 (134650), and FABPZ (134640). The results suggested that factors other than apolipoproteins and MTP are important for human intestinal chylomicron assembly and secretion. Duden (2003) noted that although endoplasmic reticulum-to-Golgi trafficking has been well characterized by both genetic and biochemical methods, few human disorders have been attributed to defects in its individual components. It is likely that the functional redundancy of the COPII pathway leads to nonlethal phenotypes that have escaped classification. Three disorders due to defects in this system are CMRD disease, X-linked spondyloepiphyseal dysplasia tarda (313400), and combined deficiency of clotting factors V and VIII (277300). Molecular Genetics ### Mutations in the SAR1B Gene Jones et al. (2003) identified a region of apparent homozygosity on chromosome 5q31.1 that segregated with affected status in 4 families with CMRD. In 10 affected individuals from 7 families with chylomicron retention disease, Jones et al. (2003) identified homozygous or compound heterozygous mutations in the SAR1B gene (see, e.g., 607690.0001-607690.0005). Several of the patients had previously been reported (Bouma et al., 1986), Roy et al. (1987), Nemeth et al. (1995), and Dannoura et al. (1999). ### Exclusion Studies Pessah et al. (1991) provided clear genetic evidence that Anderson disease is not due to a defect in the APOB gene: RFLP studies in 2 families indicated that affected children inherited different APOB alleles from at least 1 parent. Strich et al. (1993) arrived at the same conclusion from study of a family in which 3 of 7 children with consanguineous parents were affected. All 3 suffered from diarrhea, failure to thrive, and recurrent infections during infancy. Although the symptoms disappeared later in life, biochemical disorders (e.g., low plasma levels of apolipoproteins A1 (107680) and B as well as cholesterol, resulting in avitaminosis E, plus failure to secrete chylomicrons after a fat meal) persisted. Electron microscopy of enterocytes in 1 of the patients showed accumulation of lipid vacuoles. A VNTR polymorphism linked to the APOB locus excluded that gene as the site of the mutation. INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive \- Growth retardation ABDOMEN Gastrointestinal \- Fat malabsorption \- Severe diarrhea \- Steatorrhea \- Malnutrition \- Vomiting \- Jejunal endoscopy shows white epithelium \- Small bowel enterocytes accumulate lipid droplets in membrane-bound compartments or in the cytoplasm NEUROLOGIC Peripheral Nervous System \- Neurologic deficits may occur secondarily to malabsorption \- Peripheral neuropathy \- Diminished or absent deep tendon reflexes \- Diminished vibratory sense LABORATORY ABNORMALITIES \- Hypocholesterolemia \- Deficiency of fat-soluble vitamins \- Normal serum triglycerides \- Absence of chylomicrons in lymph and plasma \- Defect in chylomicron secretion \- Hypobetalipoproteinemia MISCELLANEOUS \- Onset in infancy MOLECULAR BASIS \- Caused by mutation in the SAR1, S. cerevisiae, homolog B gene (SAR1B, 607690.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	CHYLOMICRON RETENTION DISEASE	c0795956	29,154	omim	https://www.omim.org/entry/246700	2019-09-22T16:25:47	{"doid": ["0060357"], "mesh": ["C535460"], "omim": ["246700"], "icd-10": ["E78.3"], "orphanet": ["71"], "synonyms": ["Alternative titles", "ANDERSON DISEASE", "LIPID TRANSPORT DEFECT OF INTESTINE", "HYPOBETALIPOPROTEINEMIA WITH ACCUMULATION OF APOLIPOPROTEIN B-LIKE PROTEIN IN INTESTINAL CELLS"]}
## Description Ectrodactyly (split-hand/foot malformation) associated with fibular hypoplasia/aplasia is a rare disorder that appears to be inherited in an autosomal dominant fashion with reduced penetrance and variable expression (Evans et al., 2002). A form of fibular hypoplasia/aplasia associated with oligosyndactyly and tibial campomelia has been reported (FATCO syndrome; 246570). Split-hand/foot malformation associated with tibial hypoplasia/aplasia has also been described (see SHFLD1, 119100). Clinical Features Graham and Badgley (1955) described a large Michigan family with split-hand malformation occurring in 6 individuals over 2 generations, 2 of whom also had ulnar and fibular anomalies. One was a 3-month-old girl, born of a mother with right split-hand malformation and hypoplasia of the first ray of her right foot; the infant had severe deformities of both upper extremities, with right monodactyly and left split-hand, as well as bilateral ulnar aplasia and failure of ossification of the distal portion of the right clavicle. The other was a 19-month-old boy, born of a father with right split-hand; the infant had right split-hand and severe bilateral deformities of the lower extremities, including bowing and shortening of the right femur with congenital dislocation and acetabular changes, bilateral fibular aplasia, oligodactyly of both feet, and clubfeet. Deragna et al. (1966) reported a large pedigree in which aplasia of the fibula and ectrodactyly segregated over 4 generations. The proband was a male infant born with bilateral ectrodactyly ('lobster claw' deformity) of the hands, bilateral total aplasia of the fibulae with shortening and bowing of the tibiae and severe deformity of the tibio-talar joint, with almost complete rotation of the feet. There were no femoral abnormalities, and examination revealed no dysmorphic features or abnormalities of other organ systems. His sister had only fibular aplasia, whereas their father had only right-sided split-hand/foot malformation. Reconstruction of the pedigree with the help of family members showed that there were 4 family members who had only fibular aplasia, 1 who had only ectrodactyly, and 2 who had both. Deragna et al. (1966) suggested that this family might represent recessive inheritance. Lewin and Opitz (1986) reviewed fibular development and noted that fibular aplasia/hypoplasia is the most common malformation of the long bones. Commenting on the pedigree reported by Deragna et al. (1966), they stated that the fact that an individual with only ectrodactyly, whose transmitting mother was unaffected, had a son with ectrodactyly and fibular agenesis and a daughter with only fibular agenesis argued against the 2 traits segregating independently. Lewin and Opitz (1986) concluded that the phenotype represented a pleiotropic autosomal dominant trait of variable expressivity with reduced penetrance of approximately 50%. In a 25-year-old woman, Genuardi et al. (1990) observed hypoplasia of the phalanges of both hands, ectrodactyly in both feet, and nearly complete absence of the fibulae bilaterally. The middle phalanx was particularly small in the right index finger, and in the left hand, the second and third fingers had only rudimentary phalanges. The craniofacial and axial skeleton was normal, as were the femora. In a male second cousin, very mild defects of the hands and feet were observed, with normal ulnae, femora, and fibulae. Genuardi et al. (1990) noted that such milder manifestations were not seen in any of the cases of Deragna et al. (1966). Halal (1991) reported monozygotic male twins in which one had right fibular aplasia and the other had ectrodactyly of the right hand. The first twin had right-sided absence of the fibula, bowed tibia, absent talus and calcaneus, and 1 absent metatarsal and corresponding toe; his upper extremities and left lower extremity were normal. The second twin had anomalies of the right hand, including absence of 1 metacarpal, absence or hypoplasia of phalanges of the second and fourth digits, and fusion of proximal phalanges 2 and 3 and fusion of distal phalanges 4 and 5; his left upper extremity and both lower extremities were uninvolved. Renal ultrasound was normal in both boys. The parents and 2 older sibs were unaffected. Halal (1991) noted that the ectrodactyly in the second twin, which included acral anomalies, might represent 'hypodactyly;' or, if the missing metacarpal was a central ray, it might be considered a mild split-hand anomaly. Evans et al. (2002) described male infant twins, reportedly monozygotic, 1 of whom had a short, angulated left tibia with fibular aplasia, slightly shortened right tibia and fibula, absence of the second digital ray bilaterally and also of the third ray on the left. Radiologic examination of his hands at 10 months of age showed that carpal ossification on the right was not as well advanced as on the left, and that the right third and fourth metacarpals were slightly hypoplastic, measuring 1 mm narrower than those on the left. His twin brother had no congenital abnormalities, and there was no family history of limb deficiencies or other congenital malformations. Gieruszczak-Bialek et al. (2006) reported an infant girl with severe ectrodactyly and fibular aplasia who also had ulnar hypoplasia. There were no femoral defects and the craniofacial and axial skeleton appeared normal. The authors noted that using the scale developed by Evans et al. (2002) to determine severity of the syndrome, the score for this patient would be 11, in contrast to the average severity score of 5.4 for reported cases. Menke et al. (2008) reported a Dutch male infant with normal upper limbs but bilateral hypoplastic femora, fibular aplasia, and short, bowed tibiae, with ectrodactyly of the feet. An unrelated Dutch male infant also had normal upper extremities and normal left leg and foot; however, he had fibular aplasia on the right with a short, bowed tibia and a 3-toed foot with a hypoplastic second ray. Both infants had normal abdominal organs by ultrasonography. Inheritance Evans et al. (2002) published a tabular listing of 48 reported cases of fibular aplasia with ectrodactyly, including 23 sporadic and 25 familial cases from 8 pedigrees. The sex ratio was biased toward males, especially in apparently sporadic cases, and was attributed largely to a lower penetrance rate in females. Both affected males and females had affected children, but the risk to offspring was higher when the mother carried the gene, consistent with a mixed model for genetic susceptibility, i.e., the penetrance of the major predisposing gene is acting against a multifactorially determined level of liability. Evans et al. (2002) concluded that the penetrance of this disorder is significantly reduced, especially in females. They stated that although there seemed to be good evidence for a major autosomal predisposing gene, the precise pattern of inheritance is complex. The increased risk to the offspring of affected mothers was consistent with a multifactorial threshold model, and the normalization of the sex ratio in familial cases, i.e., those who would presumably have higher liability on the basis of several affected individuals, was also compatible with such a model (Fraser, 1998). Males and right-sided limbs appeared to be less well buffered against the deleterious effect of the mutation(s) involved. The authors postulated that stochastic factors might stress the developing embryo, increasing the likelihood that a predisposed infant would fail to develop normal limbs. The finding of 4 monozygous twins (2 discordant and 1 concordant) and another discordant dizygous twin among the small number of cases identified with fibular aplasia-ectrodactyly may not be unusual. Menke et al. (2008) reviewed the 8 family pedigrees previously tabulated by Evans et al. (2002) and concluded that only 2, the families originally reported by Graham and Badgley (1955) and Deragna et al. (1966), convincingly represented familial ectrodactyly with fibular aplasia. The 2 families demonstrated typical split-hand/foot malformation (SHFM) combined with fibular aplasia present in at least 1 patient, multiple affected limbs, and multiple family members affected in at least 2 generations. Menke et al. (2008) suggested, however, that the 2 families may have had typical autosomal dominant SHFM (see SHFM1, 183600) with occasional expression of ulnar and/or fibular aplasia, thus representing an allelic variant of an SHFM subtype. INHERITANCE \- Autosomal dominant SKELETAL Limbs \- Fibular aplasia/hypoplasia \- Ulnar aplasia/hypoplasia Hands \- Hypoplastic phalanges of hands \- Split-hand malformation Feet \- Ectrodactyly of feet MISCELLANEOUS \- Incomplete penetrance \- Variable expressivity ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	BRACHYDACTYLY-ECTRODACTYLY WITH FIBULAR APLASIA OR HYPOPLASIA	c1862100	29,155	omim	https://www.omim.org/entry/113310	2019-09-22T16:44:04	{"mesh": ["C537930"], "omim": ["113310"], "orphanet": ["1118"]}
Plasma cell granuloma is a lesional pattern of inflammatory pseudotumour, different from the "inflammatory myofibroblastic tumor" pattern. It is linked to IgG4-related disease.[1] ## Contents * 1 Pathology * 2 Localization * 3 See also * 4 References ## Pathology[edit] Histologically, the lesions consisted of a proliferation of mature plasma cells and reticulo-endothelial cells supported by a stroma of granulation tissue, with varying degrees of myxoid change or collagenization. Angioinvasion within the lesion is observed in 50% of cases.[2] Immunohistochemical staining reveals the IgG-predominant polyclonal nature of the plasma cells, indicating a reactive inflammatory process rather than a neoplastic one. Electron microscopy confirms the benign nature of the plasma cells with fibroblast and myofibroblast proliferation admixed with that of other inflammatory cells. ## Localization[edit] * Lung[3][4] ## See also[edit] * Pulmonary hyalinizing granuloma ## References[edit] 1. ^ Dias, O. M.; Kawassaki Ade, M; Haga, H; Cukier, A; Carvalho, C. R. (2011). "Immunoglobulin G4-related systemic sclerosing disease in a patient with sclerosing cholangitis, inflammatory pseudotumors of the lung and multiple radiological patterns: A case report". Clinics (Sao Paulo, Brazil). 66 (11): 1983–6. doi:10.1590/s1807-59322011001100021. PMC 3203974. PMID 22086532. 2. ^ Nonomura, A; Mizukami, Y; Matsubara, F; Shimizu, J; Oda, M; Watanabe, Y; Kamimura, R; Takashima, T; Kitagawa, M (1992). "Seven patients with plasma cell granuloma (inflammatory pseudotumor) of the lung, including two with intrabronchial growth: An immunohistochemical and electron microscopic study". Internal Medicine (Tokyo, Japan). 31 (6): 756–65. doi:10.2169/internalmedicine.31.756. PMID 1392177. 3. ^ Nonomura, A; Mizukami, Y; Matsubara, F; Shimizu, J; Oda, M; Watanabe, Y; Kamimura, R; Takashima, T; Kitagawa, M (1992). "Seven patients with plasma cell granuloma (inflammatory pseudotumor) of the lung, including two with intrabronchial growth: An immunohistochemical and electron microscopic study". Internal Medicine (Tokyo, Japan). 31 (6): 756–65. doi:10.2169/internalmedicine.31.756. PMID 1392177. 4. ^ Balachandran, A; Shivbalan, S (2004). "Plasma cell granuloma of the lung". Indian Pediatrics. 41 (3): 292–3. PMID 15064526. This medical sign article is a stub. You can help Wikipedia by expanding it. * v * t * e This oncology article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Plasma cell granuloma	c0018199	29,156	wikipedia	https://en.wikipedia.org/wiki/Plasma_cell_granuloma	2021-01-18T18:41:00	{"mesh": ["D006104"], "wikidata": ["Q99440225"]}
A number sign (#) is used with this entry because aminoglycoside-induced deafness is associated with mutations in at least 2 mitochondrial-encoded genes, including MTRNR1 (561000) and MTCO1 (516030). Description The mechanism of ototoxicity of aminoglycosides is thought to be interference with the production of ATP in the mitochondria of hair cells in the cochlea (Akiyoshoi et al., 1976). The aminoglycosides include kanamycin, gentamicin, tobramycin, and neomycin in addition to streptomycin. Inheritance Familial occurrence of streptomycin hearing loss, often with seemingly modest dosage of the antibiotic, was reported by Johnsonbaugh et al. (1974), Podvinec and Stefanovic (1966), Prazic and Salaj (1975), and Tsuiki and Murai (1971). The cases of Johnsonbaugh et al. (1974) involved mother and son. Viljoen et al. (1983) described 8 persons with streptomycin ototoxicity in a large kindred of mixed ancestry from a remote rural area of South Africa. In each, severe permanent perceptive hearing loss developed during antituberculous therapy with streptomycin sulfate in conventional doses. The authors favored autosomal dominant inheritance. Higashi (1989) reviewed published pedigrees in which 2 or more members had streptomycin-induced hearing loss and concluded that ordinary mendelian inheritance could not account for the findings. The disorder seemed to be transmitted almost exclusively through females. In only 2 of 28 families were there instances of affected father and children. Higashi (1989) favored mitochondrial inheritance. Hu et al. (1991) analyzed 36 pedigrees in 1 district in Shanghai and showed that susceptibility to antibiotic ototoxicity was transmitted by females exclusively. An analysis of 18 other published pedigrees confirmed this conclusion, indicating that this disorder is mitochondrially determined. This situation is comparable to that in familial chloramphenicol toxicity (515000). Molecular Genetics The mitochondrial ribosome in the cochlea is the most likely target of aminoglycoside ototoxicity, since the 'natural target' of aminoglycosides is the evolutionarily related bacterial ribosome. In bacterial studies, regions of the small ribosomal RNA appear to be important in translational fidelity. Thus, the mitochondrial rRNA genes, and especially the 12S rRNA gene (MTRNR1; 561000), were prime candidates for the site of the mtDNA mutation in maternally inherited aminoglycoside-induced deafness. In affected members of 3 families with maternally inherited aminoglycoside-induced deafness and in a large Israeli-Arab pedigree with possible combined autosomal and mitochondrial inheritance (see 221745), Prezant et al. (1993) identified a mutation in the 12S rRNA gene (1555A-G; 561000.0001). Yuan et al. (2005) identified cosegregation of a mutation in the MTCO1 gene (7444G-A; 516030.0001) and a 1555A-G mutation in the MTRNR1 gene in 9 affected members of a 3-generation Chinese family with aminoglycoside-induced sensorineural hearing loss. One additional family member with both mutations, who had a history of exposure to noise but not to aminoglycoside, exhibited mild hearing impairment. The dose and age at the time of drug administration seemed to be correlated with the severity of the hearing loss. Animal Model Kalinec et al. (2005) demonstrated that supplementation of pregnant guinea pigs with L-carnitine prevented neonatal mortality and gentamicin-induced sensorineural hearing loss in their offspring. Experiments with auditory cell lines showed that gentamicin-induced toxicity was mediated by activation of the MAPK (176948) signaling pathway through upregulation of harakiri (HRK; 603447). L-carnitine prevented gentamicin-induced upregulation of Hrk and apoptosis via JNK1 (MAPK8; 601158). Studies with small interfering RNA (siRNA) showed that Hrk upregulation was necessary for gentamicin-induced apoptosis. INHERITANCE \- Mitochondrial HEAD & NECK Ears \- Hearing loss, aminoglycoside-induced METABOLIC FEATURES \- Streptomycin ototoxicity MOLECULAR BASIS \- Caused by mutation in the mitochondrial 12S rRNA gene (MTRNR1, 561000.0001 ) \- Caused by mutation in the mitochondrial cytochrome c oxidase I gene (MTCO1, 516030.0001 ) \- Caused by mutation in the mitochondrial tRNA-ser 1 gene (MTTS1, 590080.0002 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	DEAFNESS, AMINOGLYCOSIDE-INDUCED	c1838854	29,157	omim	https://www.omim.org/entry/580000	2019-09-22T16:16:46	{"mesh": ["C564013"], "omim": ["580000"], "orphanet": ["168609"], "synonyms": ["Mitochondrial isolated sensorineural deafness with susceptibility to aminoglycoside exposure", "STREPTOMYCIN OTOTOXICITY", "Mitochondrial non-syndromic neurosensory hearing loss with susceptibility to aminoglycoside exposure", "Mitochondrial isolated neurosensory hearing loss with susceptibility to aminoglycoside exposure", "Mitochondrial non-syndromic neurosensory deafness with susceptibility to aminoglycoside exposure", "Mitochondrial isolated neurosensory deafness with susceptibility to aminoglycoside exposure", "DEAFNESS, STREPTOMYCIN-INDUCED", "Alternative titles", "Mitochondrial non-syndromic sensorineural hearing loss with susceptibility to aminoglycoside exposure", "Mitochondrial isolated sensorineural hearing loss with susceptibility to aminoglycoside exposure"], "genereviews": ["NBK1434", "NBK1422"]}
Phocomelia-ectrodactyly-deafness-sinus arrhythmia syndrome is characterised by phocomelia (involving arms more severely), ectrodactyly, ear anomalies (bilateral anomalies of the pinnae), conductive deafness, dysmorphism (long and prominent philtrum, mild maxillary hypoplasia) and sinus arrhythmia. It has been described in four patients (a father and his son and a mother and her daughter) from two unrelated families. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Phocomelia-ectrodactyly-deafness-sinus arrhythmia syndrome	c1868390	29,158	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2878	2021-01-23T17:10:11	{"gard": ["4323"], "mesh": ["C537498"], "omim": ["171480"], "umls": ["C1868390"], "icd-10": ["Q87.2"], "synonyms": ["Phocomelia-ectrodactyly-hearing loss-sinus arrhythmia syndrome", "Stoll-Lévy-Francfort syndrome"]}
Hermansky-Pudlak syndrome (HPS) affects multiple body systems and includes bleeding and visual problems, and abnormally light coloring of the skin, hair, and eyes (oculocutaneous albinism). Other symptoms may include immune problems, lung scarring (pulmonary fibrosis), and colitis. Symptoms of pulmonary fibrosis may get worse over time, and people with HPS are at increased risk for skin cancer. There are ten types of HPS each caused by a different non-working gene. This condition is inherited in an autosomal recessive fashion. HPS is diagnosed based on the symptoms and confirmed by genetic testing. Treatment is based on managing the symptoms. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Hermansky-Pudlak syndrome	c0079504	29,159	gard	https://rarediseases.info.nih.gov/diseases/6643/hermansky-pudlak-syndrome	2021-01-18T18:00:02	{"mesh": ["D022861"], "omim": ["203300"], "orphanet": ["79430"], "synonyms": ["HPS", "Albinism with hemorrhagic diathesis and pigmented reticuloendothelial cells", "Hermansky Pudlak syndrome"]}
Nausea due to pregnancy Not to be confused with mourning sickness. Morning sickness Other namesNausea and vomiting of pregnancy, nausea gravidarum, emesis gravidarum, pregnancy sickness SpecialtyObstetrics SymptomsNausea, vomiting[1] ComplicationsWernicke encephalopathy, esophageal rupture[1] Usual onset4th week of pregnancy[2] DurationUntil 16th week of pregnancy[2] CausesUnknown[2] Diagnostic methodBased on symptoms after other causes have been ruled out[3] Differential diagnosisHyperemesis gravidarum[1] PreventionPrenatal vitamins[3] TreatmentDoxylamine and pyridoxine[3][4] Frequency~75% of pregnancies[4][5] Morning sickness, also called nausea and vomiting of pregnancy (NVP), is a symptom of pregnancy that involves nausea or vomiting.[1] Despite the name, nausea or vomiting can occur at any time during the day.[2] Typically the symptoms occur between the 4th and 16th week of pregnancy.[2] About 10% of women still have symptoms after the 20th week of pregnancy.[2] A severe form of the condition is known as hyperemesis gravidarum and results in weight loss.[1][6] The cause of morning sickness is unknown but may relate to changing levels of the hormone human chorionic gonadotrophin.[2] Some have proposed that morning sickness may be useful from an evolutionary point of view.[1] Diagnosis should only occur after other possible causes have been ruled out.[3] Abdominal pain, fever, or headaches are typically not present in morning sickness.[1] Taking prenatal vitamins before pregnancy may decrease the risk.[3] Specific treatment other than a bland diet may not be required for mild cases.[2][6][3] If treatment is used the combination of doxylamine and pyridoxine is recommended initially.[3][4] There is limited evidence that ginger may be useful.[3][7] For severe cases that have not improved with other measures methylprednisolone may be tried.[3] Tube feeding may be required in women who are losing weight.[3] Morning sickness affects about 70–80% of all pregnant women to some extent.[4][5] About 60% of women experience vomiting.[2] Hyperemesis gravidarum occurs in about 1.6% of pregnancies.[1] Morning sickness can negatively affect quality of life, result in decreased ability to work while pregnant, and result in health-care expenses.[3] Generally, mild to moderate cases have no effect on the baby.[1] Most severe cases also have normal outcomes.[1] Some women choose to have an abortion due to the severity of symptoms.[1] Complications such as Wernicke encephalopathy or esophageal rupture may occur, but very rarely.[1] ## Contents * 1 Signs and symptoms * 2 Cause * 3 Pathophysiology * 3.1 Hormone changes * 3.2 Defense mechanism * 4 Treatments * 4.1 Medications * 4.2 Alternative medicine * 5 History * 5.1 Thalidomide * 6 References ## Signs and symptoms[edit] About 66% of women have both nausea and vomiting while 33% have just nausea.[1] ## Cause[edit] The cause of morning sickness is unknown but may relate to changing levels of estrogen and the hormone human chorionic gonadotrophin.[2][8] Some have proposed that morning sickness may be useful from an evolutionary point of view, arguing that morning sickness may protect both the pregnant woman and the developing embryo just when the fetus is most vulnerable.[1] Diagnosis should only occur after other possible causes have been ruled out.[3] Abdominal pain, fever, or headaches are typically not present in morning sickness.[1] Nausea and vomiting may also occur with molar pregnancy.[9] Morning sickness is related to diets low in cereals and high in sugars, oilcrops, alcohol and meat.[10] ## Pathophysiology[edit] ### Hormone changes[edit] Pathophysiology of vomiting in pregnancy * An increase in the circulating level of the hormone estrogen.[11] However, there is no consistent evidence of differences in estrogen levels and levels of bilirubin between women that experience sickness and those that do not.[12] Related to increased estrogen levels, a similar form of nausea is also seen in some women who use hormonal contraception or hormone replacement therapy. * An increase in progesterone relaxes the muscles in the uterus, which prevents early childbirth, but may also relax the stomach and intestines, leading to excess stomach acids and gastroesophageal reflux disease (GERD). * An increase in human chorionic gonadotropin. It is probably not the HCG itself that causes the nausea. More likely, it is the HCG stimulating the maternal ovaries to secrete estrogen, which in turn causes the nausea.[13] ### Defense mechanism[edit] Morning sickness may be an evolved trait that protects the baby against toxins ingested by the mother. Evidence in support of this theory includes:[14][15] * Morning sickness is very common among pregnant women, which argues in favor of its being a functional adaptation and against the idea that it is a pathology. * Fetal vulnerability to toxins peaks at around 3 months, which is also the time of peak susceptibility to morning sickness. * There is a good correlation between toxin concentrations in foods, and the tastes and odors that cause revulsion. Women who have no morning sickness are more likely to miscarry.[16] This may be because such women are more likely to ingest substances that are harmful to the fetus.[17] In addition to protecting the fetus, morning sickness may also protect the mother. A pregnant woman's immune system is suppressed during pregnancy, presumably to reduce the chances of rejecting tissues of her own offspring.[18] Because of this, animal products containing parasites and harmful bacteria can be especially dangerous to pregnant women. There is evidence that morning sickness is often triggered by animal products including meat and fish.[19] If morning sickness is a defense mechanism against the ingestion of toxins, the prescribing of anti-nausea medication to pregnant women may have the undesired side effect of causing birth defects or miscarriages by encouraging harmful dietary choices.[14] ## Treatments[edit] There is a lack of good evidence to support the use of any particular intervention for morning sickness.[20] ### Medications[edit] A number of antiemetics are effective and safe in pregnancy including: pyridoxine/doxylamine, antihistamines (such as diphenhydramine), metoclopramide, and phenothiazines (such as promethazine).[21][22] With respect to effectiveness it is unknown if one is superior to another.[21] In the United States and Canada, the doxylamine-pyridoxine combination (as Diclegis in US and Diclectin in Canada) is the only approved pregnancy category "A" prescription treatment for nausea and vomiting of pregnancy.[22] Ondansetron may be beneficial, but there are some concerns regarding an association with cleft palate,[23] and there is little high quality data.[21] Metoclopramide is also used and relatively well tolerated.[24] Evidence for the use of corticosteroids is weak.[25] ### Alternative medicine[edit] Some studies support the use of ginger, but overall the evidence is limited and inconsistent.[3][7][20][26][8] Safety concerns have been raised regarding its anticoagulant properties.[27][28][8][29] ## History[edit] ### Thalidomide[edit] Thalidomide was originally developed and prescribed as a cure for morning sickness in West Germany, but its use was discontinued when it was found to cause birth defects.[30] The United States Food and Drug Administration never approved thalidomide for use as a cure for morning sickness.[31] ## References[edit] 1. ^ a b c d e f g h i j k l m n o "Practice Bulletin No. 153: Nausea and Vomiting of Pregnancy". Obstetrics and Gynecology. 126 (3): e12–24. September 2015. doi:10.1097/AOG.0000000000001048. PMID 26287788. 2. ^ a b c d e f g h i j Festin, M (3 June 2009). "Nausea and vomiting in early pregnancy". BMJ Clinical Evidence. 2009. PMC 2907767. PMID 21726485. 3. ^ a b c d e f g h i j k l m "Practice Bulletin Summary No. 153: Nausea and Vomiting of Pregnancy". Obstetrics and Gynecology. 126 (3): 687–8. September 2015. doi:10.1097/01.aog.0000471177.80067.19. PMID 26287781. 4. ^ a b c d Koren, G (December 2014). "Treating morning sickness in the United States--changes in prescribing are needed". American Journal of Obstetrics and Gynecology. 211 (6): 602–6. doi:10.1016/j.ajog.2014.08.017. PMID 25151184. 5. ^ a b Einarson, Thomas R.; Piwko, Charles; Koren, Gideon (2013-01-01). "Prevalence of nausea and vomiting of pregnancy in the USA: a meta analysis". Journal of Population Therapeutics and Clinical Pharmacology. 20 (2): e163–170. ISSN 1710-6222. PMID 23863545. 6. ^ a b "Pregnancy". Office on Women's Health. September 27, 2010. Archived from the original on 10 December 2015. Retrieved 5 December 2015. 7. ^ a b Matthews, A; Haas, DM; O'Mathúna, DP; Dowswell, T (8 September 2015). "Interventions for nausea and vomiting in early pregnancy". The Cochrane Database of Systematic Reviews (9): CD007575. doi:10.1002/14651858.CD007575.pub4. PMC 4004939. PMID 26348534. 8. ^ a b c Viljoen, Estelle; Visser, Janicke; Koen, Nelene; Musekiwa, Alfred (2014-03-19). "A systematic review and meta-analysis of the effect and safety of ginger in the treatment of pregnancy-associated nausea and vomiting". Nutrition Journal. 13: 20. doi:10.1186/1475-2891-13-20. ISSN 1475-2891. PMC 3995184. PMID 24642205. 9. ^ Verberg, MF; Gillott, DJ; Al-Fardan, N; Grudzinskas, JG (2005). "Hyperemesis gravidarum, a literature review". Human Reproduction Update. 11 (5): 527–39. doi:10.1093/humupd/dmi021. PMID 16006438. 10. ^ Pepper, GV; Craig Roberts, S (2006). "Rates of nausea and vomiting in pregnancy and dietary characteristics across populations". Proceedings of the Royal Society B. 273 (1601): 2675–2679. doi:10.1098/rspb.2006.3633. PMC 1635459. PMID 17002954. 11. ^ Lagiou, P; Tamimi, R; Mucci, LA; Trichopoulos, D; Adami, HO; Hsieh, CC (April 2003). "Nausea and vomiting in pregnancy in relation to prolactin, estrogens, and progesterone: a prospective study". Obstetrics and Gynecology. 101 (4): 639–44. doi:10.1016/s0029-7844(02)02730-8. PMID 12681864. S2CID 13103469. 12. ^ Elizabeth Bauchner; Wendy Marquez. "Morning Sickness: Coping With The Worst". NY Metro Parents Magazine. Archived from the original on 2008-12-04. Retrieved 2008-07-06. 13. ^ Niebyl, Jennifer R. (2010). "Nausea and Vomiting in Pregnancy". New England Journal of Medicine. 363 (16): 1544–1550. doi:10.1056/NEJMcp1003896. PMID 20942670. 14. ^ a b Nesse, Randolphe M; Williams, George C (1996). Why We Get Sick (1st ed.). New York: Vintage Books. p. 290. 15. ^ Pepper GV, Craig Roberts S (October 2006). "Rates of nausea and vomiting in pregnancy and dietary characteristics across populations". Proceedings of the Royal Society B. 273 (1601): 2675–2679. doi:10.1098/rspb.2006.3633. PMC 1635459. PMID 17002954. 16. ^ Chan, Ronna L.; Olshan, A. F.; Savitz, D. A.; Herring, A. H.; Daniels, J. L.; Peterson, H. B.; Martin, S. L.; et al. (Sep 22, 2010). "Severity and duration of nausea and vomiting symptoms in pregnancy and spontaneous abortion". Human Reproduction. 25 (11): 2907–12. doi:10.1093/humrep/deq260. PMC 3140259. PMID 20861299. Archived from the original on 2011-12-13. 17. ^ Sherman, Paul W.; Flaxman, Samuel M. (2002). "Nausea and vomiting of pregnancy in an evolutionary perspective". Am J Obstet Gynecol. 186 (5): S190–S197. CiteSeerX 10.1.1.611.7889. doi:10.1067/mob.2002.122593. PMID 12011885. 18. ^ Haig, David (October 1993). "Genetic conflicts in human pregnancy". Quarterly Review of Biology. 68 (4): 495–532. doi:10.1086/418300. PMID 8115596. S2CID 38641716. 19. ^ Flaxman, Samuel M.; Sherman, Paul W. (June 2000). "Morning sickness: a mechanism for protecting mother and embryo". Quarterly Review of Biology. 75 (2): 113–148. doi:10.1086/393377. PMID 10858967. S2CID 28668687. 20. ^ a b Matthews, A; Haas, DM; O'Mathúna, DP; Dowswell, T (8 September 2015). "Interventions for nausea and vomiting in early pregnancy". The Cochrane Database of Systematic Reviews (9): CD007575. doi:10.1002/14651858.CD007575.pub4. PMC 4004939. PMID 26348534. 21. ^ a b c Jarvis, S; Nelson-Piercy, C (Jun 17, 2011). "Management of nausea and vomiting in pregnancy". BMJ (Clinical Research Ed.). 342: d3606. doi:10.1136/bmj.d3606. PMID 21685438. S2CID 32242306. 22. ^ a b Clark SM, Dutta E, Hankins GD (September 2014). "The outpatient management and special considerations of nausea and vomiting in pregnancy". Semin Perinatol. 38 (14): 496–502. doi:10.1053/j.semperi.2014.08.014. PMID 25267280. 23. ^ Koren, G (October 2012). "Motherisk update. Is ondansetron safe for use during pregnancy?". Canadian Family Physician. 58 (10): 1092–3. PMC 3470505. PMID 23064917. 24. ^ Tan, PC; Omar, SZ (April 2011). "Contemporary approaches to hyperemesis during pregnancy". Current Opinion in Obstetrics and Gynecology. 23 (2): 87–93. doi:10.1097/GCO.0b013e328342d208. PMID 21297474. S2CID 11743580. 25. ^ Poon, SL (October 2011). "Towards evidence-based emergency medicine: Best BETs from the Manchester Royal Infirmary. BET 2: Steroid therapy in the treatment of intractable hyperemesis gravidarum". Emergency Medicine Journal. 28 (10): 898–900. doi:10.1136/emermed-2011-200636. PMID 21918097. S2CID 6667779. 26. ^ Thomson, M.; Corbin, R.; Leung, L. (2014). "Effects of Ginger for Nausea and Vomiting in Early Pregnancy: A Meta-Analysis". The Journal of the American Board of Family Medicine. 27 (1): 115–122. doi:10.3122/jabfm.2014.01.130167. ISSN 1557-2625. PMID 24390893. 27. ^ Borrelli F, Capasso R, Aviello G, Pittler MH, Izzo AA (2005). "Effectiveness and safety of ginger in the treatment of pregnancy-induced nausea and vomiting". Obstetrics and Gynecology. 105 (4): 849–56. doi:10.1097/01.AOG.0000154890.47642.23. PMID 15802416. S2CID 1607109. 28. ^ Tiran, Denise (Feb 2012). "Ginger to reduce nausea and vomiting during pregnancy: Evidence of effectiveness is not the same as proof of safety". Complementary Therapies in Clinical Practice. 18 (1): 22–25. doi:10.1016/j.ctcp.2011.08.007. ISSN 1744-3881. PMID 22196569. 29. ^ Hu, Youchun; Amoah, Adwoa N.; Zhang, Han; Fu, Rong; Qiu, Yanfang; Cao, Yuan; Sun, Yafei; Chen, Huanan; Liu, Yanhua; Lyu, Quanjun (2020-01-14). "Effect of ginger in the treatment of nausea and vomiting compared with vitamin B6 and placebo during pregnancy: a meta-analysis". The Journal of Maternal-Fetal & Neonatal Medicine. 0: 1–10. doi:10.1080/14767058.2020.1712714. ISSN 1476-7058. PMID 31937153. 30. ^ Cohen, Wayne R., ed. (2000). Cherry and Merkatz's complications of pregnancy (5th ed.). Lippincott Williams & Wilkins. p. 124. ISBN 9780683016734. 31. ^ Bren L (2001-02-28). "Frances Oldham Kelsey: FDA Medical Reviewer Leaves Her Mark on History". FDA Consumer. U.S. Food and Drug Administration. Retrieved 2009-12-23. Classification D * ICD-10: O21.0 * ICD-9-CM: 643.0 * MeSH: D048968 External resources * MedlinePlus: 003119 * v * t * e Pathology of pregnancy, childbirth and the puerperium Pregnancy Pregnancy with abortive outcome * Abortion * Ectopic pregnancy * Abdominal * Cervical * Interstitial * Ovarian * Heterotopic * Embryo loss * Fetal resorption * Molar pregnancy * Miscarriage * Stillbirth Oedema, proteinuria and hypertensive disorders * Gestational hypertension * Pre-eclampsia * HELLP syndrome * Eclampsia Other, predominantly related to pregnancy Digestive system * Acute fatty liver of pregnancy * Gestational diabetes * Hepatitis E * Hyperemesis gravidarum * Intrahepatic cholestasis of pregnancy Integumentary system / dermatoses of pregnancy * Gestational pemphigoid * Impetigo herpetiformis * Intrahepatic cholestasis of pregnancy * Linea nigra * Prurigo gestationis * Pruritic folliculitis of pregnancy * Pruritic urticarial papules and plaques of pregnancy (PUPPP) * Striae gravidarum Nervous system * Chorea gravidarum Blood * Gestational thrombocytopenia * Pregnancy-induced hypercoagulability Maternal care related to the fetus and amniotic cavity * amniotic fluid * Oligohydramnios * Polyhydramnios * Braxton Hicks contractions * chorion / amnion * Amniotic band syndrome * Chorioamnionitis * Chorionic hematoma * Monoamniotic twins * Premature rupture of membranes * Obstetrical bleeding * Antepartum * placenta * Circumvallate placenta * Monochorionic twins * Placenta accreta * Placenta praevia * Placental abruption * Twin-to-twin transfusion syndrome Labor * Amniotic fluid embolism * Cephalopelvic disproportion * Dystocia * Shoulder dystocia * Fetal distress * Locked twins * Nuchal cord * Obstetrical bleeding * Postpartum * Pain management during childbirth * placenta * Placenta accreta * Preterm birth * Postmature birth * Umbilical cord prolapse * Uterine inversion * Uterine rupture * Vasa praevia Puerperal * Breastfeeding difficulties * Low milk supply * Cracked nipples * Breast engorgement * Childbirth-related posttraumatic stress disorder * Diastasis symphysis pubis * Postpartum bleeding * Peripartum cardiomyopathy * Postpartum depression * Postpartum psychosis * Postpartum thyroiditis * Puerperal fever * Puerperal mastitis Other * Concomitant conditions * Diabetes mellitus * Systemic lupus erythematosus * Thyroid disorders * Maternal death * Sexual activity during pregnancy * Category Authority control * NDL: 00568956 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Morning sickness	c0312416	29,160	wikipedia	https://en.wikipedia.org/wiki/Morning_sickness	2021-01-18T18:39:29	{"mesh": ["D048968"], "umls": ["C0312416"], "icd-9": ["643.0"], "icd-10": ["O21.0"], "wikidata": ["Q1068134"]}
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: "Urogenital neoplasm" – news · newspapers · books · scholar · JSTOR (September 2017) (Learn how and when to remove this template message) Urogenital neoplasm SpecialtyOncology, genitourinary oncology A urogenital neoplasm is a tumor of the urogenital system.[1] ## Types[edit] Types include: * Cancer of the breast and female genital organs: (Breast cancer, Vulvar cancer, Vaginal cancer, Vaginal tumors, Cervical cancer, Uterine cancer, Endometrial cancer, Ovarian cancer) * Cancer of the male genital organs (Carcinoma of the penis, Prostate cancer, Testicular cancer) * Cancer of the urinary organs (Renal cell carcinoma, Bladder cancer) ## References[edit] 1. ^ Kurman, Robert J. (2013). Blaustein's Pathology of the Female Genital Tract. Springer Science & Business Media. p. 168. ISBN 9781475738896. Retrieved 12 September 2017. ## External links[edit] Classification D * ICD-10: C50-C68 D24-D30.9 * MeSH: D014565 * v * t * e Overview of tumors, cancer and oncology Conditions Benign tumors * Hyperplasia * Cyst * Pseudocyst * Hamartoma Malignant progression * Dysplasia * Carcinoma in situ * Cancer * Metastasis * Primary tumor * Sentinel lymph node Topography * Head and neck (oral, nasopharyngeal) * Digestive system * Respiratory system * Bone * Skin * Blood * Urogenital * Nervous system * Endocrine system Histology * Carcinoma * Sarcoma * Blastoma * Papilloma * Adenoma Other * Precancerous condition * Paraneoplastic syndrome Staging/grading * TNM * Ann Arbor * Prostate cancer staging * Gleason grading system * Dukes classification Carcinogenesis * Cancer cell * Carcinogen * Tumor suppressor genes/oncogenes * Clonally transmissible cancer * Oncovirus * Carcinogenic bacteria Misc. * Research * Index of oncology articles * History * Cancer pain * Cancer and nausea * v * t * e Tumors of the female urogenital system Adnexa Ovaries Glandular and epithelial/ surface epithelial- stromal tumor CMS: * Ovarian serous cystadenoma * Mucinous cystadenoma * Cystadenocarcinoma * Papillary serous cystadenocarcinoma * Krukenberg tumor * Endometrioid tumor * Clear-cell ovarian carcinoma * Brenner tumour Sex cord–gonadal stromal * Leydig cell tumour * Sertoli cell tumour * Sertoli–Leydig cell tumour * Thecoma * Granulosa cell tumour * Luteoma * Sex cord tumour with annular tubules Germ cell * Dysgerminoma * Nongerminomatous * Embryonal carcinoma * Endodermal sinus tumor * Gonadoblastoma * Teratoma/Struma ovarii * Choriocarcinoma Fibroma * Meigs' syndrome Fallopian tube * Adenomatoid tumor Uterus Myometrium * Uterine fibroids/leiomyoma * Leiomyosarcoma * Adenomyoma Endometrium * Endometrioid tumor * Uterine papillary serous carcinoma * Endometrial intraepithelial neoplasia * Uterine clear-cell carcinoma Cervix * Cervical intraepithelial neoplasia * Clear-cell carcinoma * SCC * Glassy cell carcinoma * Villoglandular adenocarcinoma Placenta * Choriocarcinoma * Gestational trophoblastic disease General * Uterine sarcoma * Mixed Müllerian tumor Vagina * Squamous-cell carcinoma of the vagina * Botryoid rhabdomyosarcoma * Clear-cell adenocarcinoma of the vagina * Vaginal intraepithelial neoplasia * Vaginal cysts Vulva * SCC * Melanoma * Papillary hidradenoma * Extramammary Paget's disease * Vulvar intraepithelial neoplasia * Bartholin gland carcinoma * v * t * e * Tumors of the male urogenital system Testicles Sex cord– gonadal stromal * Sertoli–Leydig cell tumour * Sertoli cell tumour * Leydig cell tumour Germ cell G * Seminoma * Spermatocytic tumor * Germ cell neoplasia in situ NG * Embryonal carcinoma * Endodermal sinus tumor * Gonadoblastoma * Teratoma * Choriocarcinoma * Embryoma Prostate * Adenocarcinoma * High-grade prostatic intraepithelial neoplasia * HGPIN * Small-cell carcinoma * Transitional cell carcinoma Penis * Carcinoma * Extramammary Paget's disease * Bowen's disease * Bowenoid papulosis * Erythroplasia of Queyrat * Hirsuties coronae glandis * v * 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 This women's health related article is a stub. You can help Wikipedia by expanding it. * v * t * e This article about a neoplasm is a stub. You can help Wikipedia by expanding it. * v * t * e This article about a disease of the genitourinary system is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Urogenital neoplasm	c4020809	29,161	wikipedia	https://en.wikipedia.org/wiki/Urogenital_neoplasm	2021-01-18T19:10:31	{"mesh": ["D014565"], "umls": ["C4020809", "C0042065"], "icd-9": ["187"], "icd-10": ["C68", "C50", "D24", "D30.9"], "wikidata": ["Q7900855"]}
Crigler Najjar syndrome, type 1 is an inherited disorder in which bilirubin, a substance made by the liver, cannot be broken down. This condition occurs when the enzyme that normally converts bilirubin into a form that can easily be removed from the body does not work correctly. Without this enzyme, bilirubin can build up in the body and lead to jaundice and damage to the brain, muscles, and nerves. Crigler Najjar syndrome, type 1 is caused by mutations in the UGT1A1 gene. The condition is inherited in an autosomal recessive manner. Treatment relies on regular phototherapy throughout life. Blood transfusions and calcium compounds have also been used. Liver transplantation may be considered in some individuals. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Crigler Najjar syndrome, type 1	c0010324	29,162	gard	https://rarediseases.info.nih.gov/diseases/47/crigler-najjar-syndrome-type-1	2021-01-18T18:01:02	{"mesh": ["D003414"], "omim": ["218800"], "orphanet": ["79234"], "synonyms": ["Crigler-Najjar syndrome, type I"]}
Familial angiolipomatosis is a rare, genetic, subcutaneous tissue disorder characterized by the presence of benign, usually multiple, subcutaneous tumors composed of adipose tissue and blood vessels, typically manifesting as yellow, firm, circumscribed, 1-4 cm in diameter tumors located in the arms, legs and trunk, with deep extension of the lesions between muscles, tendons and joint capsules (without infiltration of these structures), in several members of a single family. Tumors may be tender or mildly painful when palpated and do not regress spontaneously. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Familial angiolipomatosis	c1859784	29,163	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=199279	2021-01-23T19:04:29	{"mesh": ["C565951"], "omim": ["206550"], "umls": ["C1859784"], "icd-10": ["D17.9"]}
Fibulo-ulnar hypoplasia-renal anomalies syndrome is characterized by fibuloulnar dysostosis with renal anomalies. It has been described in two sibs born to nonconsanguinous parents. The syndrome is lethal at birth (respiratory failure). Clinical manifestations include ear and facial anomalies (including micrognathia), symmetrical shortness of long bones, fibular agenesis and hypoplastic ulna, oligosyndactyly, congenital heart defects, and cystic or hypoplastic kidney. It is transmitted as an autosomal recessive trait. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Fibulo-ulnar hypoplasia-renal anomalies syndrome	c1856727	29,164	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2256	2021-01-23T18:20:49	{"gard": ["320"], "mesh": ["C537226"], "omim": ["228940"], "umls": ["C1856727"], "icd-10": ["Q87.8"], "synonyms": ["Saito-Kuba-Tsuruta syndrome"]}
## Clinical Features Ohdo et al. (1986) described the combination of mental retardation, congenital heart disease, blepharophimosis, blepharoptosis, and hypoplastic teeth in a brother and sister and in a daughter of their paternal aunt. They concluded that the disorder had not been reported before. Say and Barber (1987) and Biesecker (1991) reported cases. Maat-Kievit et al. (1993) reported 2 unrelated affected boys and compared their findings with those in 5 previously reported patients. Male patients had cryptorchidism and scrotal hypoplasia. Lopes and Guion-Almeida (1997) described a case of Ohdo syndrome with the additional features of cleft palate and bladder diverticula. Mhanni et al. (1998) reported vertical transmission of Ohdo syndrome from mother to son, suggestive of autosomal dominant inheritance. The possibility of X-linked or mitochondrial inheritance cannot be ruled out by this case. Taken together with the previously reported cases, the authors suggested that autosomal dominant inheritance with incomplete penetrance is most likely. Genetic heterogeneity is also possible. Stoll (1999) described a possible case of Ohdo syndrome. White et al. (2003) reported 2 cases of Ohdo syndrome, one with mild and the other with severe features, illustrating the phenotypic variability of the condition. The authors noted that all cases with the severe phenotype have been sporadic. Subtelomeric FISH studies of all chromosome arms on their 2 cases showed no abnormality. Verloes et al. (2006) described 11 patients from 8 families with a blepharophimosis-mental retardation syndrome (BMRS) phenotype and suggested a classification of BMRS into 5 groups: Group 1, del(3p) syndrome (613792); Group 2, BMRS, Ohdo type, limited to the original patients of Ohdo et al. (1986); Group 3, BMRS, SBBYS type (603736), with distinctive dysmorphic features and variable anomalies including heart defect, optic atrophy, deafness, hypoplastic teeth, cleft palate, joint limitations, and hypothyroidism; Group 4, BMRS, MKB type (300895), with coarse, triangular face; and Group 5, BMRS, Verloes type (604314), with severe microcephaly, hypsarrhythmia, adducted thumbs, cleft palate, and abnormal genitalia. Day et al. (2008) examined 8 unrelated patients with the Say-Barber-Biesecker-Young-Simpson type of Ohdo syndrome (SBBYSS; 603736) and reviewed the 25 previously reported patients reported with Ohdo syndrome. One family had a reported recurrence of the syndrome, resulting in pregnancy termination at 20 weeks' gestation. Day et al. (2008) stated that the most important clue to diagnosis is the facial gestalt and emphasized the severity of the psychomotor delay. Noting that 3 of their patients had thyroid abnormalities, they suggested that Ohdo and SYBBYS syndromes may be the same condition. Clayton-Smith et al. (2011) described SBBYSS as a variant of Ohdo syndrome. In patients with SBBYSS, they identified heterozygous mutations in the KAT6B gene (605880); however, they did not study patients reported by Ohdo et al. (1986), Say and Barber (1987), or Biesecker (1991). INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature HEAD & NECK Face \- Long, flat philtrum \- Micrognathia Ears \- Small ears \- Simple ears \- Deafness \- External auditory canal stenosis Eyes \- Blepharophimosis \- Ptosis \- Epicanthal folds \- Sparse eyebrows Nose \- Wide nasal bridge \- Depressed nasal bridge \- Short, upturned nose Mouth \- Small mouth \- Thin vermilion Teeth \- Widely spaced teeth ABDOMEN Gastrointestinal \- Feeding problems GENITOURINARY External Genitalia (Male) \- Scrotal hypoplasia Internal Genitalia (Male) \- Cryptorchidism SKELETAL \- Joint laxity Hands \- Fifth finger clinodactyly Feet \- Overriding 3rd toes SKIN, NAILS, & HAIR Hair \- Sparse eyebrows NEUROLOGIC Central Nervous System \- Mental retardation \- Seizures \- Hypotonia LABORATORY ABNORMALITIES \- Proteinuria MISCELLANEOUS \- Majority of cases have been sporadic ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	OHDO SYNDROME	c2931643	29,165	omim	https://www.omim.org/entry/249620	2019-09-22T16:25:27	{"doid": ["0060289"], "mesh": ["C537838"], "omim": ["249620"], "orphanet": ["2728"], "synonyms": ["Alternative titles", "OHDO BLEPHAROPHIMOSIS SYNDROME", "MENTAL RETARDATION, CONGENITAL HEART DISEASE, BLEPHAROPHIMOSIS, BLEPHAROPTOSIS, AND HYPOPLASTIC TEETH"]}
A number sign (#) is used with this entry because congenital disorder of glycosylation type Ig (CDG1G) is caused by homozygous or compound heterozygous mutation in the gene encoding dolichyl-P-mannose:Man-7-GlcNAc-2-PP-dolichyl-alpha-6-mannosyltransferase (ALG12; 607144) on chromosome 22q13. Description Congenital disorders of glycosylation (CDG), previously called carbohydrate-deficient glycoprotein syndromes (CDGSs), are a group of hereditary multisystem disorders first recognized by Jaeken et al. (1980). The characteristic biochemical abnormality of CDGs is the hypoglycosylation of glycoproteins, which is routinely determined by isoelectric focusing (IEF) of serum transferrin. Type I CDG comprises those disorders in which there is a defect in the assembly of lipid-linked oligosaccharides or their transfer onto nascent glycoproteins, whereas type II CDG comprises defects of trimming, elongation, and processing of protein-bound glycans. For a general discussion of CDGs, see CDG1A (212065) and CDG1B (602579). Clinical Features Chantret et al. (2002) reported a girl born of nonconsanguineous parents who presented with weak suckling, failure to thrive, hypotonia, psychomotor involvement, microcephaly, facial dysmorphism, and recurrent ear, nose, throat, and respiratory infections. Blood chemistries were normal, except for decreased IgG levels, and isoelectric focusing of serum transferrin revealed hypoglycosylation profiles characteristic of CDG type I. Zdebska et al. (2003) described subsequent severe psychomotor retardation in this patient at age 3 years. Thiel et al. (2002) reported an Indian girl with CDG Ig. She had delayed motor and mental development as an infant and presented with seizures at age 14 months. At 3.5 years, she had microcephaly, muscular hypotonia, prolonged partial thromboplastin time, supragluteal fat pads, and facial dysmorphism. Brain MRI showed widening of the side ventricles without hydrocephalus. Biochemical studies showed transferrin patterns consistent with CDG type I. Kranz et al. (2007) described a brother and sister with clinical findings including a unique short limb skeletal dysplasia, IgG deficiency, psychomotor retardation, blindness and deafness, male genital hypoplasia, immunodeficiency, generalized edema, and cardiac abnormalities. Both sibs died before 2 years of age, one of overwhelming sepsis and the other of cardiorespiratory failure related to cardiomyopathy. Fibroblast studies were suggestive of CDG Ig, and mutation analysis revealed compound heterozygosity for ALG12 mutations (607144.0003 and 607144.0004) in both sibs. Unique skeletal findings in these 2 patients were delayed ossification of cervical vertebrae and signs of a generalized epiphyseal dysplasia including lack of ossification at the pubic bones, knee epiphyses, and tali. Kranz et al. (2007) noted similarities between this phenotype and Roifman syndrome (300258), and suggested that some cases of Roifman syndrome may be congenital disorders of glycosylation. Biochemical Features By biochemical analysis, Chantret et al. (2002) showed that the fibroblasts of a patient with CDG I were deficient in their capacity to add the eighth mannose residue onto the lipid-linked oligosaccharide precursor (LLO). Further studies of this patient by Zdebska et al. (2003) showed red cell membrane band-3 (109270) abnormalities in the absence of anemia: moderate hypoglycosylation (27%) with normal mannose content, and severe hypoglycosylation (64%) with excess mannose and reduced N-acetylglucosamine residues, in fractions with low and high electrophoretic mobility, respectively. Zdebska et al. (2003) proposed that the incomplete biosynthesis of the N-linked glycan was caused primarily by persistence of the 3-linked mannose residue on the 6-mannose arm of the trimannosyl moiety. Molecular Genetics Chantret et al. (2002) screened the human ALG12 cDNA from a patient with CDG I and identified a homozygous point mutation that caused an amino acid substitution in a conserved region of the peptide sequence (F142V; 607144.0001). Both parents were found to be heterozygous for the mutation. The pathologic phenotype of the fibroblasts of the patient was largely normalized upon transduction of the wildtype gene, demonstrating that the F142V mutation was the underlying cause of CDG in this patient, which was designated CDG Ig. In the fibroblasts of a 2.5-year-old boy with CDG Ig, born of nonconsanguineous Danish parents, who presented with clinical and biochemical features similar to the patient described by Chantret et al. (2002), Grubenmann et al. (2002) demonstrated the biosynthetic intermediate GlcNAc-2-Man-7 oligosaccharide both on the lipid carrier dolichyl pyrophosphate and on newly synthesized glycoproteins, thus pointing to a defect in the ALG12 gene. Grubenmann et al. (2002) identified compound heterozygosity for mutations in ALG12 (T67M, 607144.0002; R146Q, 607144.0003). In a patient with CDG Ig, Thiel et al. (2002) identified compound heterozygosity for 2 mutations in the ALG12 gene (607144.0005 and 607144.0006). INHERITANCE \- Autosomal recessive GROWTH Weight \- Low birth weight Other \- Failure to thrive HEAD & NECK Head \- Microcephaly, progressive Face \- Facial dysmorphism \- Midface hypoplasia Ears \- Thick ears \- Sensorineural deafness (in 2 siblings) Eyes \- Retinal detachment, bilateral (in 1 patient) Nose \- Broad nose Mouth \- Thin upper lip CARDIOVASCULAR Heart \- Patent foramen ovale Vascular \- Patent ductus arteriosus CHEST Ribs Sternum Clavicles & Scapulae \- Short ribs with flared metaphyses Breasts \- Inverted nipples ABDOMEN Gastrointestinal \- Feeding difficulties GENITOURINARY External Genitalia (Male) \- Micropenis \- Hypospadias \- Hypoplastic scrotum Internal Genitalia (Male) \- Cryptorchidism SKELETAL Spine \- Delayed ossification of cervical vertebral bodies \- Butterfly vertebrae Pelvis \- Delayed ossification of pubic bone Limbs \- Rhizomelic limb shortening \- Short humerus \- Short femur \- Short tibia \- Short radius \- Ulnar deviation Hands \- Interphalangeal dislocations Feet \- Clubfoot \- Talipes equinovarus \- Duplication of talus, bilateral \- Sandal gap MUSCLE, SOFT TISSUES \- Edema present at birth NEUROLOGIC Central Nervous System \- Hypotonia \- Psychomotor retardation IMMUNOLOGY \- Frequent respiratory infections \- Hypogammaglobulinemia PRENATAL MANIFESTATIONS Amniotic Fluid \- Polyhydramnios LABORATORY ABNORMALITIES \- Abnormal glycosylation of transferrin, type 1 pattern MISCELLANEOUS \- Death in neonatal period or infancy \- Variable feature may be present MOLECULAR BASIS \- Caused by mutation in the alpha-1,6-mannosyltransferase gene (ALG12, 607144.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ig	c2931001	29,166	omim	https://www.omim.org/entry/607143	2019-09-22T16:09:35	{"doid": ["0080559"], "mesh": ["C535745"], "omim": ["607143"], "orphanet": ["79324"], "synonyms": ["Alternative titles", "CDG Ig"], "genereviews": ["NBK1332"]}
Glanzmann thrombasthenia is a bleeding disorder that is characterized by prolonged or spontaneous bleeding starting from birth. People with Glanzmann thrombasthenia tend to bruise easily, have frequent nosebleeds (epistaxis), and may bleed from the gums. They may also develop red or purple spots on the skin caused by bleeding underneath the skin (petechiae) or swelling caused by bleeding within tissues (hematoma). Glanzmann thrombasthenia can also cause prolonged bleeding following injury, trauma, or surgery (including dental work). Women with this condition can have prolonged and sometimes abnormally heavy menstrual bleeding. Affected women also have an increased risk of excessive blood loss during pregnancy and childbirth. About a quarter of individuals with Glanzmann thrombasthenia have bleeding in the gastrointestinal tract, which often occurs later in life. Rarely, affected individuals have bleeding inside the skull (intracranial hemorrhage) or joints (hemarthrosis). The severity and frequency of the bleeding episodes in Glanzmann thrombasthenia can vary greatly among affected individuals, even in the same family. Spontaneous bleeding tends to become less frequent with age. ## Frequency Glanzmann thrombasthenia is estimated to affect 1 in one million individuals worldwide, but may be more common in certain groups, including those of Romani ethnicity, particularly people within the French Manouche community. ## Causes Mutations in the ITGA2B or ITGB3 gene cause Glanzmann thrombasthenia. These genes provide instructions for making the two parts (subunits) of a receptor protein called integrin alphaIIb/beta3 (αIIbβ3). This protein is abundant on the surface of platelets. Platelets are small cells that circulate in blood and are an essential component of blood clots. During clot formation, integrin αIIbβ3 helps platelets bind together. Blood clots protect the body after injury by sealing off damaged blood vessels and preventing further blood loss. ITGA2B or ITGB3 gene mutations result in a shortage (deficiency) of functional integrin αIIbβ3. As a result, platelets cannot clump together to form a blood clot, leading to prolonged bleeding. Three types of Glanzmann thrombasthenia have been classified according to the amount of integrin αIIbβ3 that is available. People with type I (the most common type) have less than 5 percent of normal integrin αIIbβ3 levels, people with type II have between 5 and 20 percent of normal integrin αIIbβ3 levels, and people with the variant type have adequate integrin αIIbβ3 levels but produce only nonfunctional integrin. Some people with Glanzmann thrombasthenia do not have an identified mutation in either the ITGA2B or ITGB3 gene; the cause of the disorder in these individuals is unknown. ### Learn more about the genes associated with Glanzmann thrombasthenia * ITGA2B * ITGB3 ## 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Glanzmann thrombasthenia	c0040015	29,167	medlineplus	https://medlineplus.gov/genetics/condition/glanzmann-thrombasthenia/	2021-01-27T08:25:35	{"gard": ["2478"], "mesh": ["D013915"], "omim": ["273800"], "synonyms": []}
COASY protein-associated neurodegeneration (CoPAN) is a very rare, slowly progressive form of neurodegeneration with brain iron accumulation (NBIA) characterized by classic NBIA features. The clinical manifestations include early-onset spastic-dystonic paraparesis, oromandibular dystonia, dysarthria, parkinsonism, axonal neuropathy, progressive cognitive impairment, complex motor tics, and obsessive-compulsive disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	COASY protein-associated neurodegeneration	c3810230	29,168	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=397725	2021-01-23T18:24:05	{"gard": ["12571"], "omim": ["615643"], "icd-10": ["G23.0"], "synonyms": ["CoPAN", "NBIA6", "Neurodegeneration with brain iron accumulation due to COASY mutation"]}
Biemond (1934) described a syndrome consisting of brachydactyly (due to one short metacarpal and metatarsal), nystagmus and cerebellar ataxia in 4 generations of a family. Mental deficiency and strabismus were also present. Only a few members of the family had the full syndrome. Additional families are needed before this combination can be considered a single gene syndrome. Limbs \- Brachydactyly (one short metacarpal and metatarsal) Neuro \- Cerebellar ataxia \- Mental deficiency Eyes \- Nystagmus \- Strabismus Inheritance \- ? Autosomal dominant ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	BRACHYDACTYLY-NYSTAGMUS-CEREBELLAR ATAXIA	c1862099	29,169	omim	https://www.omim.org/entry/113400	2019-09-22T16:44:06	{"mesh": ["C566192"], "omim": ["113400"], "orphanet": ["1246"]}
Neutral lipid storage disease with myopathy is a condition in which fats (lipids) are stored abnormally in organs and tissues throughout the body. The accumulation of fats in muscle tissue leads to muscle weakness (myopathy). This condition is caused by mutations in the PNPLA2 gene. It is inherited in an autosomal recessive pattern. There is currently no treatment to correct the underlying metabolic problem. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Neutral lipid storage disease with myopathy	c1853136	29,170	gard	https://rarediseases.info.nih.gov/diseases/10288/neutral-lipid-storage-disease-with-myopathy	2021-01-18T17:58:43	{"mesh": ["C565192"], "omim": ["610717"], "umls": ["C1853136"], "orphanet": ["98908"], "synonyms": ["NLSDM", "Neutral lipid storage disease without ichthyosis"]}
This article needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the article and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed. Find sources: "Zadik–Barak–Levin syndrome" – news · newspapers · books · scholar · JSTOR (October 2020) Zadik–Barak–Levin syndrome Other namesDermoid cysts, hypothyroidism, cleft palate and hypodontia Zadik–Barak–Levin syndrome (ZBLS) is a congenital disorder in humans. Presenting conditions include primary hypothyroidism, cleft palate, hypodontia, and ectodermal dysplasia. It is the result of an embryonic defect in the mesodermal-ectodermal midline development. ## Contents * 1 Signs and symptoms * 2 Diagnosis * 3 Management * 4 References * 5 Further reading * 6 External links ## Signs and symptoms[edit] * anodontia/oligodontia—no teeth or fewer teeth than normal * cleft palate * depressed nasal bridge * dry skin * ectopic/agenesis/hypoplastic thyroid * epibulbar dermoid * frontal bossing * hypertelorism * hypothyroidy * lordosis * macroglossia * microcephaly * micrognatia/retrognatia—small or recessed jaw(s) * polyhydramnios * short stature/dwarfism * sparse/absent scalp hair(generalized) * squint/paresis of ocular muscles * umbilical hernia ## Diagnosis[edit] This section is empty. You can help by adding to it. (August 2017) ## Management[edit] This section is empty. You can help by adding to it. (August 2017) ## References[edit] * Zadik, Z. and Y. Barak, S. Levin, Z. Josephberg, J. Lustmann, J. Chemke. "Dermoid cysts, hyperthyroidism, cleft palate, and hypodontia," J. Clin. Dysmorphol., 1983 Winter, 1(4):24–7. * Zadik Barak Levin syndrome, About rare diseases, Orphanet. ## Further reading[edit] * "Zadik Barak Levin syndrome \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 13 August 2017. ## External links[edit] Classification D * MeSH: C536721 External resources * Orphanet: 2263 This article about a congenital malformation is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Zadik–Barak–Levin syndrome	c2931298	29,171	wikipedia	https://en.wikipedia.org/wiki/Zadik%E2%80%93Barak%E2%80%93Levin_syndrome	2021-01-18T19:09:46	{"gard": ["340"], "mesh": ["C536721"], "umls": ["C2931298"], "orphanet": ["2263"], "wikidata": ["Q8064158"]}
Pearson syndrome is characterized by refractory sideroblastic anemia, vacuolization of bone marrow precursors and exocrine pancreatic dysfunction. ## Epidemiology Approximately 60 cases have been described. Both sexes are affected. ## Clinical description Hematological signs begin in infancy, although a few neonatal cases have been described. These signs include macrocytic sideroblastic anemia, sometimes associated with potentially deep neutropenia or thrombocytopenia. The presence of vacuolization in granulous and erythroblastic progenitors, visible on the myelogram, is highly suggestive of the syndrome. Perls coloration reveals the presence of ringed sideroblasts. Besides the hematological deficiency, patients present with fibrotic exocrine pancreatic dysfunction with malabsorption and diarrhea, or a defect in oxidative phosphorylation resulting in lactic academia (sometimes intermittent) and an increased lactate/pyruvate ratio. Other organs can be affected, either simultaneously or during the course of the disease: frequent renal involvement with tubulopathy and aminoaciduria is observed, as well as hepatic involvement with hepatomegalia, cytolysis and cholestasis, endocrine gland disturbances, neuromuscular disorders and, in few cases, cardiac involvement and splenic atrophy. The overall pleiotropic clinical picture is evocative of the ``illegitimate'' association of multiple organ disorders in a single patient. ## Etiology Physiopathologically, this syndrome is a mitochondrial cytopathy. It is caused by mitochondrial DNA deletions, which constitute a diagnostic criterion. These deletions lead to a deficiency in mitochondrial respiratory chain function. The random distribution of mitochondrial DNA during cell division is responsible for the presence of both normal and mutated DNA in a single cell. This coexistence, named heteroplasmy, explains the high variability in clinical expression observed both between patients and between the various organs of an affected subject. Indeed, pathological manifestations occur when some level of mutated DNA has accumulated in a given tissue. ## Genetic counseling Although maternal transmission has been described, Pearson syndrome is typically sporadic. ## Management and treatment There is no specific treatment of Pearson syndrome. Management is symptomatic and includes treatment of infectious episodes and of metabolic accidents, transfusion in case of deep anemia (sometimes associated with erythropoietin therapy), uptake of pancreatic extracts and management of endocrine disorders. ## Prognosis Death often occurs before the age of three years, due to septic risks, metabolic crisis with lactic acidosis or hepatocellular failure. Patients who survive early infancy typically undergo phenotypic evolution: hematological manifestations spontaneously resolve, whereas neurological and myopathic signs either appear or worsen. Some patients develop typical Kearns-Sayre syndrome (KSS) with ophthalmoplegia, ataxia, pigmentary retinitis, conduction defects and myopathy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Pearson syndrome	c0342784	29,172	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=699	2021-01-23T17:19:50	{"gard": ["7343"], "omim": ["557000"], "umls": ["C0342773", "C0342784"], "icd-10": ["D64.0"]}
Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne potentially severe hemorrhagic disease caused by Old World Hantaviruses characterized by high fever, malaise, headache, myalgia, arthralgia, backache, abdominal pain, oliguria/renal failure and systemic hemorrhagic manifestations. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Hemorrhagic fever-renal syndrome	c2930957	29,173	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=340	2021-01-23T18:31:02	{"mesh": ["D006480", "C535630"], "umls": ["C0019101", "C2930957"], "icd-10": ["A98.5+", "N08.0*"], "synonyms": ["Hantavirosis", "Hantavirus fever"]}
## Summary ### Clinical characteristics. Mandibulofacial dysostosis with microcephaly (MFDM) is characterized by malar and mandibular hypoplasia, microcephaly (congenital or postnatal onset), intellectual disability (mild, moderate, or severe), malformations of the external ear, and hearing loss that is typically conductive. Associated craniofacial malformations may include cleft palate, choanal atresia, zygomatic arch cleft (identified on cranial CT scan), and facial asymmetry. Other relatively common findings (present in 25%-35% of individuals) can include cardiac anomalies, thumb anomalies, esophageal atresia/tracheoesophageal fistula, short stature, spine anomalies, and epilepsy. ### Diagnosis/testing. The diagnosis of MFDM is confirmed in a proband with typical clinical findings and a heterozygous pathogenic variant in EFTUD2 identified by genetic testing. ### Management. Treatment of manifestations: Individualized treatment of craniofacial manifestations is managed by a multidisciplinary team which may include: oromaxillofacial surgery, plastic surgery, otolaryngology, dentistry/orthodontics, and occupational and speech/language therapy. Newborn infants may have airway compromise at delivery due to choanal atresia and/or mandibular hypoplasia, requiring intubation and/or tracheostomy for initial stabilization. Esophageal atresia/tracheoesophageal fistula, cardiac defects, renal anomalies, and thumb anomalies are treated in a routine manner. Short stature is managed expectantly. Treatment of hearing loss is individualized, and may involve conventional hearing aid(s), bone-anchored hearing aid(s), and/or cochlear implant(s). Early individualized educational and therapy plans are devised as needed to optimize developmental outcome. Surveillance: Annual growth assessment and periodic developmental assessment with evaluation for obstructive sleep apnea and epilepsy as needed. ### Genetic counseling. MFDM is an autosomal dominant disorder. Most individuals diagnosed with MFDM to date are presumed to have the disorder as the result of a de novo EFTUD2 pathogenic variant; in some individuals, the causative pathogenic variant was inherited from a parent with a milder phenotypic presentation. If a parent of the proband has the pathogenic variant identified in the proband, the risk to sibs of the proband (at conception) is 50%. Once the causative EFTUD2 pathogenic variant has been identified in an affected family member, prenatal testing and preimplantation genetic testing are possible. ## Diagnosis ### Suggestive Findings Mandibulofacial dysostosis with microcephaly (MFDM) should be suspected in individuals with mandibulofacial dysostosis (a developmental disorder of the first and second branchial arches characterized by malar and maxillary hypoplasia) in the context of one or more additional features, including: * Microcephaly (defined here as occipitofrontal circumference ≥2 SD below mean), which may be either primary (i.e., congenital; present a birth) or secondary (i.e., postnatal onset) * Intellectual disability, which may be mild, moderate, or severe * Characteristic malformations of the external ear (see Figure 1), which include microtia (grades I-III), deficiency of the superior helix and antihelix, preauricular tags, and auditory canal atresia/stenosis. The posterior-inferior margin of the lobule may have a right-angle ("squared-off") configuration. * Hearing loss, typically conductive #### Figure 1. Range of external ear findings in MFDM. Microtia may be of any degree, and is frequently accompanied by preauricular tag(s) and/or auditory canal atresia/stenosis. The superior helix is relatively deficient. The posterior-inferior rim of the lobule may (more...) ### Establishing the Diagnosis The diagnosis of MFDM is established in a proband with typical clinical findings and a heterozygous pathogenic variant in EFTUD2 identified by genetic testing (see Table 1). Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing, multigene panel) and comprehensive genomic testing (exome sequencing, exome array, genome sequencing) depending on the phenotype. Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the clinical phenotype of MFDM varies, individuals with highly characteristic clinical findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those with an atypical or nonspecific clinical phenotype overlapping other inherited syndromes are more likely to be diagnosed using comprehensive genomic testing (see Option 2). #### Option 1 When the phenotypic and laboratory findings suggest the diagnosis of MFDM, molecular genetic testing approaches can include single-gene testing or use of a multigene panel: * Single-gene testing. Sequence analysis of EFTUD2 is performed first to detect small intragenic deletions/insertions and missense, nonsense, and splice site variants. Note: Depending on the sequencing method used, single-exon, multiexon, or whole-gene deletions/duplications may not be detected. If no variant is detected by the sequencing method used, the next step is to perform gene-targeted deletion/duplication analysis to detect exon and whole-gene deletions or duplications. * A multigene panel that includes EFTUD2 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For this disorder, a multigene panel that also includes deletion/duplication analysis is recommended (see Table 1). For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. #### Option 2 When the phenotype is indistinguishable from many other inherited disorders with similar craniofacial features or is not considered because an individual has atypical phenotypic features, comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is the best option. Exome sequencing is most commonly used; genome sequencing is also possible. If exome sequencing is not diagnostic, other techniques (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by sequence analysis (see Table 1). For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. ### Table 1. Molecular Genetic Testing Used in MFDM View in own window Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method EFTUD2Sequence analysis 393% 4 Gene-targeted deletion/duplication analysis 57% 4 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on allelic variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. Gordon et al [2012], Lines et al [2012], Need et al [2012], Luquetti et al [2013], Voigt et al [2013], Lehalle et al [2014], Deml et al [2015], Gandomi et al [2015], Sarkar et al [2015], Smigiel et al [2015], Huang et al [2016], Vincent et al [2016], Bick et al [2017], Matsuo et al [2017], McDermott et al [2017], Rengasamy Venugopalan et al [2017], Williams et al [2017], Paderova et al [2018], Yu et al [2018], Lacour et al [2019], Silva et al [2019], Wu et al [2019] 5\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. ## Clinical Characteristics ### Clinical Description Mandibulofacial dysostosis with microcephaly (MFDM) is a multiple malformation syndrome comprising craniofacial skeletal anomalies, microcephaly, developmental delay / intellectual disability, abnormalities of the ears and hearing, and, in some instances, extracranial malformations (esophageal atresia, congenital heart defects, thumb anomalies), and/or short stature. To date, 126 individuals have been identified with a pathogenic variant in EFTUD2 [Gordon et al 2012, Lines et al 2012, Need et al 2012, Luquetti et al 2013, Voigt et al 2013, Lehalle et al 2014, Deml et al 2015, Gandomi et al 2015, Sarkar et al 2015, Smigiel et al 2015, Huang et al 2016, Vincent et al 2016, Bick et al 2017, Matsuo et al 2017, McDermott et al 2017, Rengasamy Venugopalan et al 2017, Williams et al 2017, Paderova et al 2018, Yu et al 2018, Lacour et al 2019, Silva et al 2019, Wu et al 2019]. The following description of the phenotypic features associated with this condition is based on these reports. ### Table 2. Mandibulofacial Dysostosis with Microcephaly (MFDM): Frequency of Select Features View in own window Feature% of Persons w/FeatureComment Facial structural differencesMalar hypoplasia92% Micrognathia / Mandibular hypoplasia93% Cleft palate43% Choanal atresia30% Facial asymmetry58% Microcephaly87%Occipitofrontal circumference ≥2 SD below mean Developmental delay / Intellectual disability97%Severity varies (may be mild, moderate, or severe; critical sequelae (e.g. neonatal airway compromise, cardiac anomalies) may affect developmental outcome. Ear malformations & hearing lossMicrotia / Dysplastic pinna(e)97% Auditory canal atresia or stenosis68% Preauricular tag50% Hearing loss83% Other findingsCardiac anomalies35%Typically atrial &/or ventricular septal defect Thumb anomalies34%Typically proximally placed; uncommonly, preaxial polydactyly or hypoplasia Esophageal atresia / Tracheoesophageal fistula33% Short stature30% Spine anomalies28%Incl scoliosis, kyphosis, hemivertebrae, & cervical segmentation anomalies Epilepsy26% Mandibulofacial dysostosis is characterized by malar and maxillary hypoplasia. Accompanying findings in MFDM include micrognathia/mandibular hypoplasia, cleft palate, and/or choanal abnormality. Cleft palate in MFDM occurs as a Robin sequence, characterized by a midline bony defect without accompanying cleft lip. Submucous cleft has also been described. Choanal atresia is generally osseous, being either unilateral or bilateral; choanal stenosis is also frequent. Zygomatic arch cleft has been identified in ten of 19 individuals assessed (best done with cranial CT with 3-D reconstruction). Characteristic dysmorphic features (Figure 2), distinct from those seen in the other mandibulofacial and acrofacial dysostoses (see Differential Diagnosis), are recognizable by early childhood. In addition to malar and maxillary hypoplasia, microcephaly, and the typical ear anomalies described in this section, features include metopic ridge, prominent glabella, broad nasal bridge with prominent ridge and bulbous tip, large oral aperture, everted lower lip, and/or (frequently) facial asymmetry. #### Figure 2. Typical craniofacial features of MFDM. These include micrognathia, malar hypoplasia, a relatively high nasal root with prominent ridge, everted lower lip, and (frequently) facial asymmetry. Characteristic ear malformations, present in essentially all (more...) Microcephaly is present in about 87% of reported individuals (n=33; median -3.5 SD; range -0.2 SD to -6.5 SD) [Huang et al 2016]. Cephalic growth curves for MFDM are published [Huang et al 2016]. In some instances, individuals have exhibited apparent cephalic "catch-up" growth, resulting in a normal adult occipitofrontal circumference despite microcephaly in childhood. Individuals whose head circumference falls within the normal range have also been reported to have intellectual disability [Luquetti et al 2013, Lehalle et al 2014]. Developmental delay and/or intellectual disability are present in almost all individuals. Among 30 persons on whom data are available, the degree of intellectual disability was reported as "mild" (~40%), "moderate" (~50%), or "severe" (~10%) [Gordon et al 2012, Lines et al 2012, Luquetti et al 2013, Voigt et al 2013]. Affected children are ambulatory but show delayed motor development, taking first steps at a median age of 26 months (n=38; range 13-60 months) [Huang et al 2016]. Among those who are verbal, the median reported age at first words is 27 months (n=32; range 12 months to 5.6 years); some affected persons remain nonverbal into adult life [Huang et al 2016]. Assessment of language skills may be confounded by the presence of hearing loss and/or cleft palate. To date there have been no detailed or cross-sectional studies of long-term neuropsychological outcomes in MFDM. Developmental data in the few affected adults identified to date suggest a broad range of outcomes, with some affected persons achieving semi-independent living with paid employment [Huang et al 2016], whereas others are nonverbal and require extensive assistance with daily activities [Authors, unpublished data]. Ear malformations and hearing loss * External ear malformations. External ears are anomalous in virtually all affected individuals. Typical findings (Figure 2) include microtia (grades I-III), deficiency of the superior helix and antihelix, preauricular tags, and auditory canal atresia/stenosis. The posterior-inferior margin of the lobule may have a right-angle ("squared-off") configuration. * Middle/inner ear malformations. Ear structures (ossicles, semicircular canals) are absent and/or malformed in some individuals; this is best assessed by temporal bone CT [Gordon et al 2012, Luquetti et al 2013, Voigt et al 2013]. * Hearing loss. Hearing loss is typically conductive (~60%) as opposed to sensorineural or mixed, and is likely to result from malformation or absence of the middle ear ossicles, auditory canal atresia, or both. Other relatively common findings * Cardiac anomalies are present in 35% of individuals. Hemodynamically insignificant atrial and ventricular septal defects are the most common; tetralogy of Fallot, patent ductus arteriosus, and aortic arch abnormalities (e.g., coarctation) have also been reported [Need et al 2012, Lehalle et al 2014]. * Thumb anomalies (proximally placed, duplicated, or hypoplastic thumbs) are seen in about 35% of individuals. * Esophageal atresia / tracheoesophageal fistula (EA/TEF) is present in about 35% of affected individuals. EA/TEF is typically type C (the most common type), in which the upper esophageal pouch ends blindly and the lower esophageal pouch connects abnormally to the trachea (distal tracheoesophageal fistula). Laryngotracheal anomalies (tracheomalacia, posterior laryngotracheoesophageal clefts) may be seen in association with EA/TEF. It may be suspected antenatally because of polyhydramnios or absent stomach echolucency, or neonatally in the context of unexplained respiratory distress and/or failed nasogastric tube placement. * Short stature is present in 30% of individuals. Height growth curves for MFDM are published [Huang et al 2016]. * Spine anomalies include scoliosis, kyphosis, hemivertebrae, and cervical segmentation anomalies. * Epilepsy is present in 26% of individuals. Detailed clinical data regarding the type of epilepsy have not been specifically reported. Matsuo et al [2017] report one individual with recurrent seizures for which EEG demonstrated occasional spike discharges originating from the right frontal area. Additional malformations (low frequency) * Other CNS abnormalities. Although brain MRI imaging data is limited, in most cases individuals have a structurally normal brain (apart from microcephaly). The CNS malformations reported on rare occasion have included undergyration, cerebral atrophy, cerebellar and pontine hypoplasia, olfactory bulb agenesis, and (in 1 individual) exencephaly [Lines et al 2012, Lehalle et al 2014, Huang et al 2016, Matsuo et al 2017, Lacour et al 2019, Silva et al 2019]. * Renal anomalies include unilateral renal agenesis, vesicoureteric reflux, and ureteropelvic junction obstruction. * Other. Cryptorchidism, lacrimal system abnormalities, and epidermal dermoid have each been reported in one or a few individuals [Lines et al 2012, Luquetti et al 2013, Lehalle et al 2014]. ### Genotype-Phenotype Correlations No genotype-phenotype correlations for EFTUD2 have been identified. Individuals with microdeletions encompassing EFTUD2 and contiguous genes may have additional features or more severe intellectual disability [Lines et al 2012, Gandomi et al 2015]. ### Penetrance MFDM is highly penetrant but variably expressive. Features may be subclinical in some affected individuals, as in the case of two non-mosaic, intellectually normal mothers – each with two affected children – in whom the only reported clinical findings were unilateral zygomatic cleft and facial asymmetry [Voigt et al 2013] and mild facial asymmetry and a preauricular tag [McDermott et al 2017]. ### Nomenclature The descriptive term "mandibulofacial dysostosis with microcephaly" is synonymous with the eponym "mandibulofacial dysostosis, Guion-Almeida type" [Guion-Almeida et al 2009]. Some have suggested that MFDM be classified as an acrofacial dysostosis rather than a mandibulofacial dysostosis [Voigt et al 2013]. This is predominantly a clinical (rather than pathophysiologic) distinction based on the presence of limb anomalies in the former category, and their absence in the latter. ### Prevalence The prevalence of MFDM has not been established. At least 126 cases caused by mutation of EFTUD2 have been reported to date (see Table 2 and references cited in Clinical Description). MFDM is a pan ethnic disorder with no recognized racial or ethnic predisposition and no evidence of sex bias. ## Differential Diagnosis ### Mandibulofacial Dysostosis ### Table 3. Genes of Interest in the Differential Diagnosis of Mandibulofacial Dysostosis with Microcephaly View in own window Gene(s)DiffDx DisorderMOIClinical Characteristics of DiffDx Disorder Overlapping w/MFDMDistinguishing Features CHD7 1CHARGE syndrome (See CHD7 Disorder.)ADMicrocephaly, ear anomalies, choanal atresia, TEF, CHDOcular coloboma & Mondini malformation are present in CHARGE but not in MFDM. DHODHMiller acrofacial dysostosis (OMIM 263750)ARMFD w/postaxial limb defects ± other extracranial malformationsOFC & intelligence are typically normal in Miller acrofacial dysostosis. POLR1C POLR1D TCOF1Treacher Collins syndrome (TCS)AD AR * MFD (may resemble MFD in MFDM) * Malformations occur in 1st & 2nd branchial arch-derived structures. * ID (w/o microcephaly) is not common but may be present in some persons. 2 * Lower lid clefts, absent eyelashes, & lacrimal system anomalies may be present. * Cardiac & esophageal malformations are not assoc w/TCS. * Intellect & OFC are usually in average range in TCS. * Unlike TCS, palpebral fissures are not consistently downslanting in MFDM. RPL5 RPL11 RPL35A RPS10 RPS17 RPS19 RPS24 RPS26 3Diamond-Blackfan anemia (DBA)AD (XL 4)~1/3 of persons exhibit MFD-like craniofacial anomalies ± cleft palate, anomalous thumbs, cardiac anomalies, &/or growth restriction.Moderate-to-severe anemia in DBA SF3B4Nager acrofacial dysostosis (OMIM 154400)ADMFD w/preaxial (typically upper) limb defects, ± other extracranial malformationsOFC & intelligence typically normal in Nager acrofacial dysostosis AD = autosomal dominant; AR = autosomal recessive; CHD = congenital heart defect; DiffDx = differential diagnosis; ID = intellectual disability; MFD = mandibulofacial dysostosis; MFDM = mandibulofacial dysostosis with microcephaly; MOI = mode of inheritance; OFC = occipitofrontal circumference; TEF = tracheoesophageal fistula; XL = X-linked 1\. The finding of a CHD7 pathogenic variant is not equivalent to a diagnosis of CHARGE syndrome; the phenotypic spectrum of heterozygous CHD7 pathogenic variants encompasses CHARGE syndrome as well as subsets of features that comprise the CHARGE syndrome phenotype. 2\. Intellectual disability (without microcephaly) may be present in individuals with either (a) a history of neonatal airway compromise or (b) microdeletions encompassing TCOF1 and adjacent genes [Vincent et al 2016]. 3\. Listed genes represent the most common genetic causes of Diamond-Blackfan anemia (DBA); more than 20 genes are known to be associated with DBA (see Diamond-Blackfan anemia). 4\. DBA is most often inherited in an autosomal dominant manner; GATA1\- and TSR2-DBA are inherited in an X-linked manner (GATA1 and TSR2 are less common genetic causes of DBA and are not included in the table). ### Craniofacial Microsomia Craniofacial microsomia (CFM) is a first- and second-arch malformation spectrum encompassing several phenotypes, including oculo-auriculo-vertebral (OAV) syndrome and Goldenhar syndrome (OMIM 164210). CFM most frequently occurs as a simplex case (i.e., in a single individual in a family) with unknown etiology; recurrence risks are empiric. CFM shares several major features with mandibulofacial dysostosis with microcephaly (MFDM), including preauricular tags, microtia, aural atresia, hearing loss, and – notably – facial asymmetry, present in approximately 65% of persons with CFM and also a frequent finding in MFDM (58%). The spectrum of orofacial clefting differs between the two conditions: midline cleft palate is typical of MFDM, while CFM can be associated with any type of orofacial cleft, including lateral oral clefts. Although various extracranial anomalies may occur in either condition, vertebral anomalies in particular should suggest CFM. At least two persons with an EFTUD2 pathogenic variant were diagnosed with "bilateral OAV syndrome" prior to the recognition of MFDM as a distinct syndrome [Authors, personal observation]. ### Tracheoesophageal Fistula Tracheoesophageal fistula is a feature of several other recognized conditions, including Feingold syndrome and VACTERL association (OMIM 192350); clinical differentiation is generally straightforward. See Esophageal Atresia/Tracheoesophageal Fistula Overview for details. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with mandibulofacial dysostosis with microcephaly (MFDM), the evaluations summarized in Table 4 (if not performed as part of the evaluation that led to the diagnosis) are recommended. ### Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with MFDM View in own window System/ConcernEvaluationComment MFD * Airway assessment for evidence of upper-airway obstruction w/or w/o choanal atresia * Exam for midline cleft palate & referral to multidisciplinary cleft palate team as required Important in newborns w/disorder DD/IDDevelopmental assessmentIncl adaptive, cognitive, & speech/language evals Hearing lossAudiologic evalAssess for hearing loss. EA/TEFUrgent eval in newborns, esp in those w/history of polyhydramnios, unexplained respiratory distress, &/or failed nasogastric tube placement Cardiac anomalyEchocardiogram & cardiologist eval Renal anomalyRenal ultrasound Skeletal anomalyRadiograph to assess for scoliosis, rib or thumb malformation as clinically indicated Short statureAssess w/growth charts.Height growth curves for MFDM are published. 1 Genetic counselingBy genetics professionals 2To inform patients & their families re nature, MOI, & implications of disorder to facilitate medical & personal decision making Family support/ resourcesAssess: * Use of community or online resources such as Parent to Parent; * Need for social work involvement for parental support; * Need for home nursing referral. DD/ID = developmental delay / intellectual disability; EA/TF = esophageal atresia / tracheoesophageal fistula; MFD = mandibulofacial dysostosis; MOI = mode of inheritance 1\. Huang et al [2016] 2\. Medical geneticist, certified genetic counselor, or certified advanced genetic nurse ### Treatment of Manifestations There are no published management guidelines to date for MFDM. Esophageal atresia / tracheoesophageal fistula, cardiac defects, renal anomalies, and thumb anomalies are treated in a routine manner. Short stature is managed expectantly. Of note, the response to human growth hormone has not been specifically reported. ### Table 5. Treatment of Manifestations in Individuals with MFDM View in own window Manifestation/ConcernTreatmentConsiderations/Other Mandibulofacial dysostosis * Neonates w/airway compromise at delivery may require intubation &/or tracheostomy for initial stabilization. * Treatment of craniofacial manifestations is individualized & managed by a multidisciplinary team incl oromaxillofacial surgery, plastic surgery, otolaryngology, dentistry/orthodontics, & occupational & speech/language therapy. DD/IDSee Developmental Delay / Intellectual Disability Management Issues.To optimize developmental outcome Hearing lossTreatment is individualized & may involve conventional hearing aid(s), bone-anchored hearing aid(s), &/or cochlear implant(s).Community hearing services through early intervention or school district DD/ID = developmental delay / intellectual disability #### Developmental Delay / Intellectual Disability Management Issues The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country. Ages 0-3 years. Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy as well as infant mental health services, special educators, and sensory impairment specialists. In the US, early intervention is a federally funded program available in all states that provides in-home services to target individual therapy needs. Ages 3-5 years. In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed for those who qualify based on established motor, language, social, or cognitive delay. The early intervention program typically assists with this transition. Developmental preschool is center based; for children too medically unstable to attend, home-based services are provided. All ages. Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life. Some issues to consider: * IEP services: * An IEP provides specially designed instruction and related services to children who qualify. * IEP services will be reviewed annually to determine whether any changes are needed. * As required by special education law, children should be in the least restrictive environment feasible at school and included in general education as much as possible and when appropriate. * Hearing consultants should be a part of the child's IEP team to support access to academic material. * PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child's access to academic material. Beyond that, private supportive therapies based on the affected individual's needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician. * As a child enters the teen years, a transition plan should be discussed and incorporated in the IEP. For those receiving IEP services, the public school district is required to provide services until age 21. * A 504 plan (Section 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text. * Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a US public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities. * Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability. #### Motor Dysfunction Gross motor dysfunction * Physical therapy is recommended to maximize mobility and to reduce the risk for later-onset orthopedic complications (e.g., contractures, scoliosis, hip dislocation). * Consider use of durable medical equipment and positioning devices as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers). * For muscle tone abnormalities including hypertonia or dystonia, consider involving appropriate specialists to aid in management of baclofen, tizanidine, Botox®, antiparkinsonian medications, or orthopedic procedures. Fine motor dysfunction. Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing, and writing. Oral motor dysfunction should be assessed at each visit and clinical feeding evaluations and/or radiographic swallowing studies should be obtained for choking/gagging during feeds, poor weight gain, frequent respiratory illnesses or feeding refusal that is not otherwise explained. Assuming that the child is safe to eat by mouth, feeding therapy (typically from an occupational or speech therapist) is recommended to help improve coordination or sensory-related feeding issues. Feeds can be thickened or chilled for safety. When feeding dysfunction is severe, an NG-tube or G-tube may be necessary. Communication issues. Consider evaluation for alternative means of communication (e.g., Augmentative and Alternative Communication [AAC]) for individuals who have expressive language difficulties. An AAC evaluation can be completed by a speech-language pathologist who has expertise in the area. The evaluation will consider cognitive abilities and sensory impairments to determine the most appropriate form of communication. AAC devices can range from low-tech, such as picture exchange communication, to high-tech, such as voice-generating devices. Contrary to popular belief, AAC devices do not hinder verbal development of speech and, in many cases, can improve it. #### Social/Behavioral Concerns Children may qualify for and benefit from interventions used in treatment of autism spectrum disorder, including applied behavior analysis (ABA). ABA therapy is targeted to the individual child's behavioral, social, and adaptive strengths and weaknesses and typically performed one on one with a board-certified behavior analyst. Consultation with a developmental pediatrician may be helpful in guiding parents through appropriate behavior management strategies or providing prescription medications, such as medication used to treat attention-deficit/hyperactivity disorder (ADHD), when necessary. Concerns about serious aggressive or destructive behavior can be addressed by a pediatric psychiatrist. ### Surveillance ### Table 6. Recommended Surveillance for Individuals with MFDM View in own window System/ConcernEvaluationFrequency Mandibulofacial dysotosisEvaluate for obstructive sleep apnea.As needed Developmental delay / Intellectual disabilityDevelopmental assessment & psychoeducational testing for childrenPeriodically throughout childhood Short statureGrowth parametersAnnually throughout childhood & adolescence EpilepsyNeurologic eval w/EEG &/or brain imaging if appropriateAs needed ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Mandibulofacial Dysostosis with Microcephaly	c1864652	29,174	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK214367/	2021-01-18T21:12:50	{"mesh": ["C537405"], "synonyms": ["Mandibulofacial Dysostosis", "Guion-Almeida Type (MFDGA)"]}
For a discussion of the heritability of bone size and the genetic heterogeneity of quantitative trait loci (QTL) for bone size, see (BSZQTL1; 609656). Mapping Shen et al. (2006) studied 3,899 Caucasian individuals from 451 families to examine the relationship of areal bone size of the spine, hip, and wrist to fracture risk. Those with hip and wrist fractures had significantly larger areal bone size at the hip and wrist, respectively. In contrast, those with spine fractures had significantly smaller spine bone size. All 3 bone size variables showed strong genetic determination, with heritability estimates of 0.55 to 0.72. By genomewide analysis, Shen et al. (2006) identified significant linkage of hip bone size to chromosome 8q24 (maximum multipoint lod score of 3.27) with suggestion of an interaction with a locus on 19p13. Other candidate QTLs were identified on chromosomes 2p24, 14q21, and 16q12, but none reached statistical significance. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	BONE SIZE QUANTITATIVE TRAIT LOCUS 3	c1857711	29,175	omim	https://www.omim.org/entry/610649	2019-09-22T16:04:17	{"omim": ["610649"], "synonyms": ["Alternative titles", "BSZQTL3"]}
Granular corneal dystrophy Granular corneal dystrophy type I, Numerous irregular shaped discrete crumb-like corneal opacities SpecialtyOphthalmology Granular corneal dystrophy type II, Variable sized crumb-like opacities in the corneal stroma that have become fused in areas giving rise to elongated and stellate shapes Granular corneal dystrophy is a slowly progressive corneal dystrophy that most often begins in early childhood. Granular corneal dystrophy has two types: * Granular corneal dystrophy type I, also corneal dystrophy Groenouw type I, is a rare form of human corneal dystrophy. It was first described by German ophthalmologist Arthur Groenouw in 1890.[1] * Granular corneal dystrophy type II, also called Avellino corneal dystrophy or combined granular-lattice corneal dystrophy[2] is also a rare form of corneal dystrophy. The disorder was first described by Folberg et al. in 1988. The name Avellino corneal dystrophy comes from the first four patients in the original study each tracing their family origin to the Italian province of Avellino.[3] ## Contents * 1 Presentation * 2 Genetics * 3 Diagnosis * 4 Treatment * 5 See also * 6 References ## Presentation[edit] Granular corneal dystrophy is diagnosed during an eye examination by an ophthalmologist or optometrist. The lesions consist of central, fine, whitish granular lesions in the cornea. Visual acuity is slightly reduced. ## Genetics[edit] Granular corneal dystrophy is caused by a mutation in the TGFBI gene, located on chromosome 5q31.[4] The disorder is inherited in an autosomal dominant manner.[5] This indicates that the defective gene responsible for the disorder is located on an autosome (chromosome 5 is an autosome), and only one copy of the gene is sufficient to cause the disorder, when inherited from a parent who has the disorder. The gene TGFBI encodes the protein keratoepithelin.[5] ## Diagnosis[edit] This section is empty. You can help by adding to it. (April 2018) ## Treatment[edit] Corneal transplant is not needed except in very severe and late cases. Light sensitivity may be overcome by wearing tinted glasses. ## See also[edit] * Corneal dystrophy ## References[edit] 1. ^ Online Mendelian Inheritance in Man (OMIM): 121900 2. ^ Online Mendelian Inheritance in Man (OMIM): 607541 3. ^ Folberg R, Alfonso E, Croxatto JO, Driezen NG, Panjwani N, Laibson PR, Boruchoff SA, Baum J, Malbran ES, Fernandez-Meijide R (January 1988). "Clinically atypical granular corneal dystrophy with pathologic features of lattice-like amyloid deposits. A study of these families". Ophthalmology. 95 (1): 46–51. doi:10.1016/s0161-6420(88)33226-4. PMID 3278259. 4. ^ Munier, F. L.; Korvatska, E.; Djemaï, A.; Paslier, D. L.; Zografos, L.; Pescia, G.; Schorderet, D. F. (March 1997). "Kerato-epithelin mutations in four 5q31-linked corneal dystrophies". Nature Genetics. 15 (3): 247–251. doi:10.1038/ng0397-247. PMID 9054935. 5. ^ a b Paliwal, P.; Gupta, J.; Tandon, R.; Sharma, A.; Vajpayee, R. B. (Oct 2009). "Clinical and Genetic Profile of Avellino Corneal Dystrophy in 2 Families from North India". Archives of Ophthalmology. 127 (10): 1373–1376. doi:10.1001/archophthalmol.2009.262. PMID 19822856. * v * t * e Types of corneal dystrophy Epithelial and subepithelial * Epithelial basement membrane dystrophy * Gelatinous drop-like corneal dystrophy * Lisch epithelial corneal dystrophy * Meesmann corneal dystrophy * Subepithelial mucinous corneal dystrophy Bowman's membrane * Reis–Bucklers corneal dystrophy * Thiel-Behnke dystrophy Stroma * Congenital stromal corneal dystrophy * Fleck corneal dystrophy * Granular corneal dystrophy * Lattice corneal dystrophy * Macular corneal dystrophy * Posterior amorphous corneal dystrophy * Schnyder crystalline corneal dystrophy Descemet's membrane and endothelial * Congenital hereditary endothelial dystrophy * Fuchs' dystrophy * Posterior polymorphous corneal dystrophy * X-linked endothelial corneal dystrophy [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Granular corneal dystrophy	c0018179	29,176	wikipedia	https://en.wikipedia.org/wiki/Granular_corneal_dystrophy	2021-01-18T19:05:23	{"mesh": ["D003317"], "umls": ["C0018179"], "wikidata": ["Q5596720"]}
## Summary ### Clinical characteristics. ASPM primary microcephaly (ASPM-MCPH) is characterized by: (1) significant microcephaly (below -3 SD for age) usually present at birth and always present before age one year and (2) the absence of other congenital anomalies. While developmental milestones are usually normal in young children, older children have variable levels of intellectual disability. Neurologic examination is usually normal except for mild spasticity. Seizures are not common. ### Diagnosis/testing. The diagnosis of ASPM-MCPH is established in a proband with biallelic pathogenic variants in ASPM identified by molecular genetic testing. ### Management. Treatment of manifestations: Treatment is symptomatic and focused on interventions to address developmental delay / intellectual disability, speech delay, and behavior issues. The management of epilepsy and spasticity is as per standard care. Surveillance: Routine monitoring of: growth; response of seizures to treatment or new-onset seizures; management of spasticity; developmental progress, including speech and language development; educational needs; and behavior for anxiety, attention, and aggressive or self-injurious behavior. Assess family need for social work support (e.g., respite care, other local resources) Agents/circumstances to avoid: Limit the use of methylphenidate, which exacerbates hyperactivity. ### Genetic counseling. ASPM-MCPH is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being a heterozygote (carrier), and a 25% chance of being unaffected and not a carrier. Heterozygotes may have mild microcephaly (-2 to -3 SDs) but do not have other clinical findings associated with ASPM-MCPH. Once the ASPM pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible. ## Diagnosis ### Suggestive Findings ASPM primary microcephaly (ASPM-MCPH) should be suspected in individuals with the following clinical and neuroimaging findings. Clinical findings * Congenital microcephaly (usually identified before birth by ultrasound examination) with an occipitofrontal circumference equal to or below -2 SDs at birth, and below -3.5 SDs before age one year * Mild intrauterine growth restriction with postnatal catch up (Growth retardation does not persist after age two years.) * No other congenital abnormalities * Normal or subnormal motor development * Usually mild intellectual disability (ID) with preserved memory but variable (range: borderline normal intellectual functioning to severe ID) * Seizures (rare) * Nonspecific facial features (i.e., narrow sloping forehead) Brain MRI findings * Reduced brain volume that affects supratentorial structures, and, to a lesser extent, the cerebellum [Passemard et al 2009] and brain stem. The mean reduction of cerebral volume is 50%, affecting both the cerebral cortex and white matter; it is more pronounced in the prefrontal and cingulate cortices than in the mesial temporal regions. The volume of the hippocampus is not affected. The cortex is thicker, especially in the prefrontal region [Passemard et al 2016]. * Commonly simplified gyral pattern with reduced gyrification index and surface of the cerebral cortex [Létard et al 2018] * Mild lateral ventricle enlargement * Corpus callosum dysplasia/hypoplasia [Passemard et al 2016] * Cortical dysplasia (rare), which can be bilateral polymicrogyria [Hu et al 2014] or focal polymicrogyria [Passemard et al 2009]) and migration anomalies (heterotopias) ### Establishing the Diagnosis The diagnosis of ASPM-MCPH is established in a proband with biallelic pathogenic variants in ASPM identified by molecular genetic testing (see Table 1). Because the phenotype of ASPM-MCPH may be indistinguishable from many other primary microcephalies, recommended molecular genetic testing approaches include use of a multigene panel (see Option 1) or comprehensive genomic testing (see Option 2). Note: Single-gene testing (sequence analysis of ASPM, followed by gene-targeted deletion/duplication analysis) is rarely useful and typically NOT recommended. #### Option 1 A multigene panel that includes ASPM and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. #### Option 2 Comprehensive genomic testing does not require the clinician to determine which gene(s) are likely involved. Exome sequencing is most commonly used; genome sequencing is also possible. If exome sequencing is not diagnostic, exome array (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by sequence analysis. Note: To date such variants have not been identified as a cause of ASPM microcephaly. For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. ### Table 1. Molecular Genetic Testing Used in ASPM Primary Microcephaly View in own window Gene 1MethodProportion of Pathogenic Variants 2 Detectable by Method ASPMSequence analysis 3~98% 4 Gene-targeted deletion/duplication analysis 5Unknown 6 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on allelic variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. Data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2014] 5\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 6\. No data on detection rate of gene-targeted deletion/duplication analysis are available. ## Clinical Characteristics ### Clinical Description ASPM primary microcephaly (ASPM-MCPH) is characterized by: (1) significant microcephaly (below -3 SD for age) usually present at birth and always present before age one year and (2) the absence of another congenital anomalies. While developmental motor milestones are usually normal in young children, older children have variable levels of language delay and intellectual disability. Neurologic examination is usually normal except for mild spasticity. Fewer than 15% of affected individuals have seizures. Growth. While weight and length are most often normal at birth, intrauterine growth restriction may be present in some. Growth may be delayed within the first months of life because of transient feeding difficulties. All children have normal height after age two years. Occipitofrontal circumference (OFC). Microcephaly is often detected prior to birth, typically during the third trimester of pregnancy and rarely during the second trimester. OFC is between -2 and -8 SD at birth (32 cm and 26 cm, respectively). A clinical characteristic of ASPM-MCPH is a decline in brain growth with age such that OFC is between -4 and -14 SD in adulthood. Neurologic findings – in the absence of brain malformations – are limited to a mild pyramidal syndrome (i.e., mild spasticity of the lower limbs). Intellectual disability (ID). Early motor development is normal (in ~50%) or mildly delayed. Language is often delayed (first use of sentences after age 3 years in 80%), with poorly articulated speech or speech limited mostly to single words or short sentences. Individuals with ASPM-MCPH have mild-to-severe ID. They have preserved memory despite their ID [Passemard et al 2016]. While they may have success with vocational training in crafts or services, affected individuals are likely unable to live independently. Behavior issues. Preschool age may be very difficult because the children may become angry and hit or bite other children due to their lack of vocabulary. Before age ten to 12 years, children are easily frustrated with learning activities and appear inattentive to others or to classroom activities. Inattentiveness (inability to listen to or carry out instructions), hyperkinesia (e.g., excessive movement, inability to sit still), and impulsiveness (no sense of danger) tend to appear at an early age and become more noticeable when children start school. Such behaviors are often considered more deleterious to functioning in a classroom than speech delay. After age 12 years, hyperactivity and impulsiveness disappear. Teenagers are calmer and more attentive. They can appear introverted. They become cheerful, affable, and cooperative [Pattison et al 2000]. Autistic features have not been described in ASPM-MCPH. Epilepsy. Fewer than 15% of individuals with ASPM-MCPH have epilepsy. Epilepsy is more likely to occur when brain MRI shows cortical anomalies (polymicrogyria, cortical dysplasia). Seizures that often begin after age two years are variable: focal or tonic and tonic-clonic generalized seizures have been reported. Focal seizures should prompt the clinician to search for a focal dysplasia or unilateral polymicrogyria [Passemard et al 2009]. West syndrome has not been reported. EEG may be normal or show focal spikes. Other findings. Some individuals with ASPM-MCPH have hypo- and/or hyperpigmented macules [Létard et al 2018]. Findings that are rare, without a recurrent pattern, and are likely coincidental include: scoliosis (2 families [Létard et al 2018]), middle ear hypoplasia [Létard et al 2018], deafness [Darvish et al 2010], preaxial polydactyly [Ahmad et al 2017], unilateral cystic kidney [Passemard et al 2009], and tricuspid insufficiency [Ariani et al 2013]. ### Genotype-Phenotype Correlations No genotype-phenotype correlations have been identified. ### Nomenclature Age of onset is used to distinguish primary from secondary microcephaly. Primary microcephaly (PM) is congenital (present at birth) while secondary microcephaly refers to a normal OFC at birth followed by postnatal microcephaly. Microcephalia vera is a general term used to describe congenital microcephaly associated with neurologic features. ASPM-MCPH is also designated as MCPH5 (i.e., the 5th primary microcephaly [MCPH] locus to be identified). ### Prevalence A review of the literature in 2019 identified 685 individuals with ASPM-MCPH belonging to 321 families. Most families come from the Asian subcontinent and Middle East (Pakistan, Saudi Arabia, Egypt, and Iran). A few families are from Europe and the Americas [Létard et al 2018]. ASPM-MCPH is the most common form of primary microcephaly. To date, biallelic ASPM pathogenic variants explain 30%-50% of MCPH depending on the geographic origin of the individual and the rate of consanguinity in the population. ## Differential Diagnosis Monogenic disorders in the differential diagnosis of ASPM-MCPH include the primary microcephalies (PMs), a group of rare, phenotypically and etiologically heterogeneous disorders of brain growth characterized by (1) a head circumference close to or below -2 SD at birth and below -3 SD by age one year; (2) absence of extracephalic anomalies; and (3) mild-to-severe intellectual disability. Additional clinical or neuroimaging features can be associated. Most PMs are inherited in an autosomal recessive manner. To date, pathogenic variants in more than 100 genes are responsible for PM (for review, see Jayaraman et al [2018]). The three broad phenotypic categories of monogenic primary microcephaly include the following: * Isolated PM in which the primary microcephaly is not associated with extracerebral malformations (e.g., ASPM-MCPH, most tubulinopathies). Many PMs are also known as microcephaly primary hereditary or MCPH)* although some may have different names for historical reasons; * PM with short stature (i.e., Seckel syndrome); Syndromic PM, a heterogeneous group in which PM is associated with extracerebral anomalies and growth impairment (e.g., Rubinstein-Taybi syndrome, Cornelia de Lange syndrome, Meier-Gorlin syndrome, DYRK1A intellectual disability syndrome) * MCPH and Seckel syndrome may be further subdivided by the presence of cortical malformations and/or chorioretinopathy. Genes associated with the three broad phenotypic categories of PM (excluding those with a true clinically recognizable "syndromic gestalt" such as Rubinstein-Taybi syndrome and Cornelia de Lange syndrome) are listed in Table 2. OMIM phenotypic series referenced in Table 2 (see OMIM entries designated with the prefix "PS") are based on the presence of microcephaly and associated features. Due to the intrinsic phenotypic variability associated with pathogenic variants in each gene, the clinical overlap across these phenotypic series is considerable. Although the three broad phenotypic categories have been valuable for clinical management and for differential diagnosis, this simple classification does not reflect underlying pathophysiologic mechanisms. ### Table 2. Monogenic Disorders with Congenital Microcephaly and Intellectual Disability 1 to Consider in the Differential Diagnosis of ASPM Primary Microcephaly View in own window Disorder/PhenotypeGene(s)MOIClinical Features Distinguishing the Disorder from ASPM-MCPH MCPH (OMIM PS251200)ANKLE2 CDK5RAP2 CDK6 CENPE CENPJ CEP135 CEP152 CIT COPB2 KIF14 KNL1 MAP11 MCPH1 MFSD2A NCAPD2 NCAPD3 NCAPH NUP37 PHC1 SASS6 STIL WDFY3 WDR62 ZNF335AR (AD) 2 * ANKLE2-, CENPJ-, CEP152-, KIF14-, NCAPD2-, PHC-, & ZNF335-MCPH: may have IUGR w/subsequent short stature * MFSD2A-MCPH: may have hydrocephalus * STIL-MCPH: may have holoprosencephaly * WDR62-MCPH: often severe cortical dysplasia (DD w/the cortical malformation, complex phenotypic series) * ZNF335-MCPH: early lethality Microcephaly-micromelia syndrome (OMIM 251230)DONSONAR * Short stature * Inconstant anomalies of forearm Meier-Gorlin syndrome (OMIM PS224690)CDC45 CDC6 CDT1 GMNN MCM5 ORC1 ORC4 ORC6AR (AD) 3 * ORC1 Meier-Gorlin syndrome: short stature * Mammary hypoplasia in females * Bilateral microtia & aplasia or hypoplasia of the patellae are characteristic but inconstant. * ID uncommon Cortical dysplasia, complex, w/other brain malformations (OMIM PS614039, Congenital Fibrosis of the Extraocular Muscles, Tubulinopathies Overview)CTNNA2 KIF2A KIF5C TUBA8 TUBB TUBB2A TUBB2B TUBB3 TUBG1AD (AR) 4 * Brain dysplasia of variable severity * Fusion between caudate & putamen nuclei w/indistinct anterior arm of the internal capsule * Neonatal seizures Seckel syndrome (OMIM PS210600)ATR CENPJ CEP152 CEP63 DNA2 NIN NSMCE2 RBBP8 TRAIPAR * IUGR * Severe short stature (< -3 SD) * Microcephaly may be disproportionate (in SD) compared to height. * Beaked nose * Sloping forehead Microcephalic osteodysplastic dwarfism (MOPD) type 2 (OMIM 210720)PCNTAR * IUGR w/subsequent very short stature * Mild skeletal dysplasia * Risk of brain hemorrhages RNU4ATAC disordersRNU4ATACAR * IUGR w/subsequent short stature * Brain malformations * Ocular & auditory sensory deficit * Encompass a spectrum of 3 phenotypes: primary MOPD type 1, Roifman syndrome, & Lowry Wood syndrome Microcephaly & chorioretinopathy (MCCRP) (OMIM PS251270)PLK4 TUBGCP4 TUBGCP6AR * Chorioretinopathy (inconstant) * PLK4-MCCRP: IUGR w/subsequent short stature Microcephaly w/or w/out chorioretinopathy, lymphedema, or ID (OMIM 152950)KIF11AD * Chorioretinopathy & lymphedema (inconstant) * ID uncommon Asparagine synthetase deficiencyASNSAR * Low CSF asparagine level * Progressive encephalopathy w/cortical atrophy & seizures Serine biosynthesis defects (OMIM 601815, 614023, 610992)PHGDH PSPH PSAT1AR * Low CSF serine level * Neonatal seizures DYRK1A ID syndrome (OMIM 614104)DYRK1AAD * Distinctive facies: bitemporal narrowing, deep-set eyes, large simple ears, pointed nasal tip AD = autosomal dominant; AR = autosomal recessive; DD = developmental delay; ID = intellectual disability; IUGR = intrauterine growth restriction; MOI = mode of inheritance 1\. Disorders are associated with intellectual disability unless otherwise noted. 2\. MCPH is inherited in an autosomal recessive manner with the exception of WDFY3-MCPH, which is inherited in an autosomal dominant manner. 3\. Meier-Gorlin syndrome is inherited in an autosomal recessive manner with the exception of GMNN Meier-Gorlin syndrome, which is inherited in an autosomal dominant manner. 4\. Cortical dysplasia, complex, with other brain malformations (CDCBM) is inherited in an autosomal dominant manner with the exception of CTNNA2\- and TUBA8-CDCBM, which are inherited in an autosomal recessive manner. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with ASPM primary microcephaly (ASPM-MCPH), the evaluations summarized in Table 3 (if not performed as part of the evaluation that led to diagnosis) are recommended. ### Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with ASPM Primary Microcephaly View in own window System/ConcernEvaluationComment ConstitutionalMeasure height, weight, OFC.During 1st 2 yrs of life transient FTT is common & typically resolves spontaneously. FeedingNutrition / feeding team evaluationLow threshold for clinical feeding evaluation when showing signs of FTT NeurologicNeurologic evaluationIf seizures are a concern: * Consider an EEG. * Review brain MRI for evidence of polymicrogyria, cortical dysplasia. DevelopmentDevelopmental assessment * To incl motor, adaptive, cognitive & speech/language evaluation * Eval for early intervention / special education Psychiatric/ BehavioralNeuropsychiatric evalScreen for behavior problems incl sleep disturbances, ADHD, & anxiety. Mild spasticityOrthopedics / physical medicine & rehabi / PT/OT evaluationTo incl assessment of: * Gross motor & fine motor skills * Need for PT (to improve gross motor skills) &/or OT (to improve fine motor skills) Miscellaneous/ OtherConsultation w/clinical geneticist &/or genetic counselorTo incl genetic counseling Family supports/resourcesAssess: * Use of community or online resources such as Parent To Parent. * Need for social work involvement for parental support. ADHD = attention-deficit/hyperactivity disorder; FTT=failure to thrive; OFC = occipitofrontal circumference; OT = occupational therapy; PT = physical therapy ### Treatment of Manifestations ### Table 4. Treatment of Manifestations in Individuals with ASPM Primary Microcephaly View in own window Manifestation/ConcernTreatmentConsiderations/Other DD/IDSee Developmental Delay / Intellectual Disability Management Issues. Speech delaySpeech therapyAugmentative & Alternative Communication in case of severe oral communication disorder Behavior issuesCognitive behavioral therapyMethylphenidate seldom effective in ADHD [Author, personal observation] EpilepsyTreatment by experienced neurologist w/AEDs according to type of seizures * Usually responsive to mono or bi-therapy * Education of parents/caregivers 1 Poor weight gain / Failure to thriveFeeding therapy &/or dietary supplements to ↑ caloric intake SpasticityPhysical medicine & rehabilitation / PT/OTStretching to ↑ mobility Family/CommunityEnsure appropriate social work involvement to connect families w/local resources, respite, & support.Consider involvement in adaptive sports or Special Olympics. ADHD = attention-deficit/hyperactivity disorder; AEDs = antiepileptic drugs; DD/ID = developmental delay / intellectual disability; OT = occupational therapy; PT = physical therapy 1\. Education of parents/caregivers regarding common seizure presentations is appropriate. For information on non-medical interventions and coping strategies for children diagnosed with epilepsy, see Epilepsy & My Child Toolkit. #### Developmental Delay / Intellectual Disability Management Issues The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country. Ages 0-3 years. Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy as well as infant mental health services, special educators and sensory impairment specialists. In the US, early intervention is a federally funded program available in all states and provides in-home services to target individual therapy needs. Ages 3-5 years. In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies, and an individualized education plan (IEP) is developed for those who qualify based on established motor, language, social, or cognitive delay. The early intervention program typically assists with this transition. Developmental preschool is center-based; for children too medically unstable to attend, home-based services are provided. All ages. Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life. Some issues to consider: * Individualized education plan (IEP) services: * An IEP provides specially designed instruction and related services to children who qualify. * IEP services will be reviewed annually to determine if any changes are needed. * As required by special education law, children should be in the least restrictive environment feasible at school and included in general education as much as possible and when appropriate. * Vision and hearing consultants should be a part of the child's IEP team to support access to academic material. * PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child's access to academic material. Beyond that, private supportive therapies based on the affected individual's needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician. * As a child enters teen years, a transition plan should be discussed and incorporated in the IEP. For those receiving IEP services, the public school district is required to provide services until age 21. * A 504 plan (Section 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text. * Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities. * Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability. #### Communication Issues Consider evaluation for alternative means of communication (e.g., Augmentative and Alternative Communication [AAC]) for individuals who have expressive language difficulties. An AAC evaluation can be completed by a speech-language pathologist who has expertise in the area. The evaluation will consider cognitive abilities and sensory impairments to determine the most appropriate form of communication. AAC devices can range from low-tech, such as picture exchange communication, to high-tech, such as voice-generating devices. Contrary to popular belief, AAC devices do not hinder verbal development of speech, and in many cases can improve it. #### Motor Dysfunction Gross motor dysfunction. Physical therapy is recommended to maximize mobility and to reduce the risk for later-onset orthopedic complications (e.g., contractures, scoliosis, hip dislocation) in patients with pyramidal tract involvement. Fine motor dysfunction. Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing, and writing. #### Social/Behavioral Concerns Consultation with a developmental pediatrician may be helpful in guiding parents through appropriate behavior management strategies or providing prescription medications, such as medication used to treat attention-deficit/hyperactivity disorder, when necessary. Concerns about serious aggressive or destructive behavior can be addressed by a pediatric psychiatrist. ### Surveillance ### Table 5. Recommended Surveillance for Individuals with ASPM Primary Microcephaly View in own window System/ConcernEvaluation 1 Feeding * Measurement of growth parameters (weight, height, OFC) * Evaluation of nutritional status Neurologic * Monitor those w/seizures as clinically indicated. * Assess for new manifestations incl new-onset seizures, spasticity, contractures (rare). DevelopmentMonitor developmental progress & educational needs. Speech delayMonitor speech development. Psychiatric/ BehavioralAncillary behavior assessment for anxiety, attention, & aggressive or self-injurious behavior; referral for formal evaluation if concerns MusculoskeletalPhysical medicine, OT/PT assessment of mobility, self-help skills Miscellaneous/ OtherAssess family need for social work support (e.g., respite care, other local resources). OFC = occipitofrontal circumference; OT = occupational therapy; PT = physical therapy 1\. To be performed at each visit ### Agents/Circumstances to Avoid Use of methylphenidate should be limited, as it exacerbates hyperactivity [Author, personal data]. ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	ASPM Primary Microcephaly	None	29,177	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK555474/	2021-01-18T21:44:22	{"synonyms": ["ASPM Microcephalia Vera", "Microcephaly Primary Hereditary (MCPH 5)"]}
A number sign (#) is used with this entry because of evidence that susceptibility to schizophrenia-18 (SCZD18) is conferred by variation in the SLC1A1 gene (133550) on chromosome 9p24. One such family has been reported. For a general phenotypic description and a discussion of genetic heterogeneity of schizophrenia, see 181500. Clinical Features Myles-Worsley et al. (2013) studied a 5-generation Palauan family (kindred 3501) in which 7 members had a psychotic disorder. Some of the patients who had been diagnosed with schizophrenia had prominent mood symptoms, leading to the diagnosis of schizoaffective disorder. Mapping In several members of a Palauan family (kindred 3501) segregating schizophrenia and schizoaffective disorder, Melhem et al. (2011) identified a deletion at chromosome 9p24.2 containing the SLC21A1 glutamate transporter gene. Using quantitative PCR in an expanded sample of 21 family members, Myles-Worsley et al. (2013) confirmed the deletion of part of the SLC1A1 gene in all 7 family members with psychosis, 3 obligate carrier parents, and 1 unaffected sib, and found that 4 marry-in parents were noncarriers. Linkage analysis under an autosomal dominant model generated a lod score of 3.64, confirming cosegregation of the deletion with psychosis. Molecular Genetics In affected members of a 5-generation Palauan family (kindred 3501) segregating schizophrenia and schizoaffective disorder with a deletion at 9p24, Myles-Worsley et al. (2013) demonstrated that an 84,298-bp deletion occurs immediately upstream of the SLC1A1 gene in a regulatory region that contains the full native promoter sequence (including histone binding regions, transcription factor binding regions, and a CpG island), extends through exon 1 of the SLC1A1 mRNA, and removes the first 59 amino acids of the SLC1A1 protein (133550.0001), including the first transmembrane sodium/dicarboxylate symporter domain, one of the domains responsible for glutamate transport. The deletion was not observed in any other Palauans studied, including Palauans with psychiatric disease outside of this family. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	SCHIZOPHRENIA 18	c3808913	29,178	omim	https://www.omim.org/entry/615232	2019-09-22T15:52:53	{"omim": ["615232"], "synonyms": ["Alternative titles", "SCHIZOPHRENIA 18 WITH OR WITHOUT AN AFFECTIVE DISORDER"]}
A rare X-linked cerebellar ataxia, characterized by a combination of upper and lower motor neuron signs, with an age of onset in the first or second decade, slow progression, and normal intelligence. Typical features of cerebellar dysfunction include gait and limb ataxia, intention tremor, dysmetria, dysdiadochokinesia, dysarthria, nystagmus, and hyperreflexia. Further phenotypic features are pes cavus, scoliosis, muscle atrophy, and peripheral sensory and motor nerve abnormalities. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	X-linked progressive cerebellar ataxia	c0796205	29,179	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1175	2021-01-23T19:11:23	{"mesh": ["C563134"], "omim": ["302500"], "icd-10": ["G11.1"]}
Not to be confused with Age progression. 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: "Photoaging" – news · newspapers · books · scholar · JSTOR (December 2014) (Learn how and when to remove this template message) This article may require cleanup to meet Wikipedia's quality standards. No cleanup reason has been specified. Please help improve this article if you can. (June 2011) (Learn how and when to remove this template message) (Learn how and when to remove this template message) Photoaging or photoageing[1] (also known as "dermatoheliosis"[2]) is a term used for the characteristic changes to skin induced by chronic UVA and UVB exposure.[3]:29 Tretinoin is the best studied retinoid in the treatment of photoaging[4] The deterioration of biological functions and ability to manage metabolic stress is one of the major consequences of the aging process. Aging is a complex, progressive process that leads to functional and aesthetic changes in the skin. This process can result from both intrinsic (i.e., genetically determined) as well as extrinsic processes (i.e., environmental factors). Photoaging is attributed to continuous, long-term exposure to ultraviolet (UV) radiation of approximately 300–400 nm, either natural or synthetic, on an intrinsically aged skin. ## Contents * 1 Effects of UV light * 1.1 Molecular and genetic changes * 1.2 Pigmentation * 1.3 Immunosuppression * 1.4 Degradation of collagen * 1.5 Retinoic acids and photodamage * 2 Signs, symptoms and histopathology * 3 Defense mechanisms * 3.1 Epidermal thickness * 3.2 Pigment * 3.3 Repair of DNA mutation and apoptosis * 3.4 Tissue inhibitors of MMPs (TIMPs) * 3.5 Antioxidants * 4 Treatment * 4.1 Primary prevention * 4.2 Secondary protection * 4.3 Tertiary prevention * 5 See also * 6 References * 7 External links ## Effects of UV light[edit] ### Molecular and genetic changes[edit] UVB rays are a primary mutagen that can only penetrate through the epidermal (outermost) layer of the skin, resulting in DNA mutations. These mutations arise due to chemical changes, the formation of cyclobutane pyrimidine dimers and photoproducts formed between adjacent pyrimidine bases. These mutations may be clinically related to specific signs of photoaging such as wrinkling, increasing in elastin and collagen damage.[5][6] DNA UV mutation The epidermal layer does not contain any blood vessels or nerve endings but melanocytes and basal cells are embedded in this layer. Upon exposure to UVB rays, melanocytes will produce melanin, a pigment that gives the skin its color tone. However, UVB will cause the formation of freckles and dark spots, both of which are symptoms of photoaging. With constant exposure to UVB rays, signs of photoaging might appear and precancerous lesions or skin cancer may develop. UVA rays are able to penetrate deeper into the skin as compared to UVB rays. Hence, in addition to the epidermal layer, the dermal layer will also be damaged. The dermis is the second major layer of the skin and it comprises collagen, elastin, and extrafibrillar matrix which provides structural support to the skin. However, with constant UVA exposure, the size of the dermis layer will be reduced, thereby causing the epidermis to start drooping off the body. Due to the presence of blood vessels in the dermis, UVA rays can lead to dilated or broken blood vessels which are most commonly visible on the nose and cheeks. UVA can also damage DNA indirectly through the generation of reactive oxygen species (ROS), which include superoxide anion, peroxide and singlet oxygen. These ROS damage cellular DNA as well as lipids and proteins. ### Pigmentation[edit] UV exposure can also lead to inflammation and vasodilation which is clinically manifested as sunburn. UV radiation activates the transcription factor, NF-κB, which is the first step in inflammation. NF-κB activation results in the increase of proinflammatory cytokines, for example: interleukin 1 (IL-1), IL-6 vascular endothelial growth factor, and tumor necrosis factor (TNF-α). This then attract neutrophils which lead to an increase in oxidative damage through the generation of free radicals. Additionally, UV radiation would cause the down-regulation of an angiogenesis inhibitor, thrombospondin-1, and the up-regulation of an angiogenesis activator which is platelet-derived endothelial cell growth factor, in keratinocytes. These enhance angiogenesis and aid in the growth of UV-induced neoplasms. ### Immunosuppression[edit] It has been reported that UV radiation leads to local and systemic immunosuppression, due to DNA damage and altered cytokine expression. This has implications in cutaneous tumor surveillance. The Langerhans cells may undergo changes in quantity, morphology, and function due to UV exposure and may eventually become depleted. One proposed explanation for this immunosuppression is that the body is attempting to suppress an autoimmune response to inflammatory products resulting from UV damage.[citation needed] ### Degradation of collagen[edit] UV exposure would also lead to the activation of receptors for epidermal growth factor, IL-1, and TNF-α in keratinocytes and fibroblasts, which then activates signaling kinases throughout the skin via an unknown mechanism.[7] The nuclear transcription factor activator protein, AP-1, which controls the transcription of matrix metalloproteinases (MMP), is expressed and activated. MMP-1 is a major metalloproteinases for collagen degradation. This entire process is aided by the presence of reactive oxygen species that inhibits protein-tyrosine phosphatases via oxidation, thereby resulting in the up-regulation of the above-mentioned receptors. Another transcription factor NF-κB, which is also activated by UV light, also increases the expression of MMP-9. The up-regulation of MMP can occur even after minimal exposure to UV, hence, exposure to UV radiation which is inadequate to cause sunburn can thus facilitate the degradation of skin collagen and lead to presumably, eventual photoaging. Thus, collagen production is reduced in photoaged skin due to the process of constant degradation of collagen mediated by MMPs. In addition, the presence of damaged collagen would also down-regulate the synthesis of new collagen. The impaired spreading and attachment of fibroblasts onto degraded collagen could be one of the contributing factors to the inhibition of collagen synthesis. ### Retinoic acids and photodamage[edit] UV radiation decreases the expression of both retinoic acid receptors and retinoid X receptors in human skin, thereby resulting in a complete loss of the induction of RA-responsive genes. It also leads to an increase in activity of the AP-1 pathway, increasing MMP activity and thus resulting in a functional deficiency of vitamin A in the skin. ## Signs, symptoms and histopathology[edit] Early symptoms of photoaging: * Dyspigmentation, the formation of wrinkles and other symptoms appear around regions of skin commonly exposed to sun, mostly the eyes, mouth and forehead.[8] The lips may be affected.[8] In Canadian women, the upper chest is commonly affected.[8] * Spider veins on face and neck * Loss of color and fullness in lips Symptoms of photoaging attributed to prolonged exposure to UV: * Wrinkles deepen and forehead frown lines can be seen even when not frowning. * Telangiectasias (spider veins) most commonly seen around the nose, cheeks and chin. * Skin becomes leathery and laxity occurs. * Solar lentigines (age spots) appear on the face and hands. * Possibly pre-cancerous red and scaly spots (actinic keratoses) appear. * Cutaneous malignancies In addition to the above symptoms, photoaging can also result in an orderly maturation of keratinocytes and an increase in the cell population of the dermis where abundant; hyperplastic, elongated and collapsed fibroblasts and inflammatory infiltrates are found. Photodamage can also be characterized as a disorganization of the collagen fibrils that constitute most of the connective tissue, and the accumulation of abnormal, amorphous, elastin-containing material, a condition known as actinic elastosis. ## Defense mechanisms[edit] Endogenous defense mechanisms provide protection of the skin from damages induced by UV. ### Epidermal thickness[edit] UV exposure which would lead to an increase in epidermal thickness could help protect from further UV damage. ### Pigment[edit] It has been reported in many cases that fairer individuals who have lesser melanin pigment show more dermal DNA photodamage, infiltrating neutrophils, keratinocyte activation, IL-10 expression and increased MMPs after UV exposure. Therefore, the distribution of melanin provides protection from sunburn, photoaging, and carcinogenesis by absorbing and scattering UV rays, covering the skin lower layers and protecting them from the radiation. [9] ### Repair of DNA mutation and apoptosis[edit] The damage of DNA due to exposure of UV rays will lead to expression of p53, thereby leading to eventual arrest of the cell cycle. This allows DNA repair mediated by endogenous mechanisms like the nucleotide excision repair system. In addition, apoptosis occurs if the damage is too severe. However, the apoptotic mechanisms decline with age, and if neither DNA repair mechanism nor apoptosis occurs, cutaneous tumorigenesis may result. ### Tissue inhibitors of MMPs (TIMPs)[edit] TIMPs regulate the activity of MMP. Many studies have shown that UV rays would induce TIMP-1. ### Antioxidants[edit] The skin contains several antioxidants, including vitamin E, coenzyme Q10, ascorbate, carotenoids, superoxide dismutase, catalase, and glutathione peroxidase. These antioxidants provide protection from reactive oxygen species produced during normal cellular metabolism. However, overexposure to UV rays can lead to a significant reduction in the antioxidant supply, thus increasing oxidative stress. Hence, these antioxidants are essential in the skin's defense mechanism against UV radiation and photocarcinogenesis. ## Treatment[edit] Treatment and intervention for photoaging can be classified into a unique paradigm based on disease prevention. ### Primary prevention[edit] Primary prevention aims to reduce the risk factors before a disease or condition occurs. Sun protection is the most effective form of primary prevention of photoaging. The major methods of sun protection are sunscreen products, sun protective clothing, and reducing exposure to the sun, especially during peak sun hours (10 AM-4PM in the spring and summer seasons). Broad-spectrum sunscreen products provide optimal coverage for protection against UV damage because they protect against both types of UVA rays (UVA1 and UVA2) along with UVB rays. Proper application methods and timing are important factors in proper sunscreen use. This includes using a proper quantity of sunscreen, applying sunscreen prior to sun exposure, and consistent reapplication (especially after exposure to water or sweat).[10] ### Secondary protection[edit] Secondary protection refers to early detection of disease, potentially while still asymptomatic, to allow positive interference to prevent, delay, or attenuate the symptomatic clinical condition. This includes the following: retinoids (e.g. tretinoin), antioxidants (e.g. topical vitamin C, oral supplements, CoQ10, Lipoic acid), estrogens, growth factors and cytokines. There are various forms of topical retinoids. Tretinoin, a retinoid, is widely considered to be the most efficacious treatment for photoaging by dermatologists due to consistent evidence from several randomized clinical trials. Retinoids are vitamin A derivatives that bind to retinoic acid receptors (RARs) and retinoid X receptors (RXRs). Binding to these receptors induces a cascade of cellular processes that ultimately lead to increased collagen production and epidermal thickening, reducing the appearance of skin sagging and wrinkling. Tretinoin is also efficacious for the treatment of acne. Adapalene and tazarotene are also third-generation synthetic retinoids that are used for the treatment for acne. Adapalene has not been widely studied or proven for use in photoaging. However, it has been used off-label for that purpose. Tazarotene is been proven to be efficiacious in the treatment of photoaging. Retinoid derivatives, known as retinol and retinal, are often used in over the counter cosmeceutical products for anti-aging purposes. The form of retinol and retinal are metabolized in the skin to retinoic acid, which can then act on the RARs and RXRs.[11] These products are considered cosmeceuticals rather than drugs due to their lack of regulation, and they have not been widely studied. Furthermore, tretinoin is the most well studied and consistent in its efficacy in the treatment of photoaging.[12] ### Tertiary prevention[edit] Lastly, tertiary prevention is the treatment of an existing symptomatic disease process to ameliorate its effects or delay its progress. Such tertiary prevention includes the use of chemical peels, resurfacing techniques (e.g. micro-dermabrasion), ablative or non-ablative laser resurfacing, radio-frequency technology, soft tissue augmentation (also known as fillers),[13] and botulinum toxins. Photorejuvenation procedures are performed by dermatologists to reduce the visible symptoms. Each of these treatment modalities have primary concerns that they address. For example, botulinum injections paralyze facial muscles. This prevents muscle contraction and subsequent wrinkle formation.[14] Injectable fillers are often used in the nasolabial fold to increase volume and minimize the appearance of sagging or wrinkling. ## See also[edit] * Occlusion miliaria * List of cutaneous conditions ## References[edit] 1. ^ Helfrich, Y. S.; Sachs, D. L.; Voorhees, J. J. (Jun 2008). "Overview of skin aging and photoaging" (PDF). Dermatology Nursing / Dermatology Nurses' Association. 20 (3): 177–183, quiz 183. ISSN 1060-3441. PMID 18649702.[permanent dead link] 2. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 3. ^ James, William D.; Berger, Timothy G. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. 4. ^ Stefanaki, C.; Stratigos, A.; Katsambas, A. (2005). "Topical retinoids in the treatment of photoaging". Journal of Cosmetic Dermatology. 4 (2): 130–134. doi:10.1111/j.1473-2165.2005.40215.x. PMID 17166212. 5. ^ "Photoaging". 6. ^ http://911skin.com/uvbubarays.html 7. ^ Spiekstra, SW; Breetveld; Rustemeyer; Scheper; Gibbs (September 2007). "Wound-healing factors secreted by epidermal keratinocytes and dermal fibroblasts in skin substitutes". Wound Repair and Regeneration. 15 (5): 708–17. doi:10.1111/j.1524-475X.2007.00280.x. PMID 17971017. "The secretion of proinflammatory cytokines (IL-1alpha, TNF-alpha), chemokine/mitogen (CCL5) and angiogenic factor (vascular endothelial growth factor) by epidermal substitutes and tissue remodeling factors (tissue inhibitor of metalloproteinase-2, hepatocyte growth factor) by dermal substitutes was not influenced by keratinocyte-fibroblast interactions. The full-skin substitute has a greater potential to stimulate wound healing than epidermal or dermal substitutes. Both epidermal-derived IL-1alpha and TNF-alpha are required to trigger the release of dermal-derived inflammatory/angiogenic mediators from skin substitutes." 8. ^ a b c "Photoaging". Canadian Dermatology Association. Canadian Dermatology Association. Retrieved 14 May 2018. 9. ^ https://www.isdin.com/en-US/blog/skincare/anti-aging/what-is-photoaging-and-why-do-we-have-to-care-about-it/ 10. ^ "UpToDate". www.uptodate.com. Retrieved 2018-04-14. 11. ^ Cosmetic dermatology. Alam, Murad., Gladstone, Hayes B., Tung, Rebecca C. Edinburgh: Saunders. 2009. ISBN 978-0702031434. OCLC 771939884.CS1 maint: others (link) 12. ^ Stefanaki, Christina (August 3, 2005). "Topical Retinoids in the Treatment of Photoaging". Journal of Cosmetic Dermatology. 4 (2): 130–134. doi:10.1111/j.1473-2165.2005.40215.x. PMID 17166212. 13. ^ Trivisonno, A.; Rossi, A.; Monti, M.; Di Nunno, D.; Desouches, C.; Cannistra, C.; Toietta, G. (2017). "Facial skin rejuvenation by autologous dermal microfat transfer in photoaged patients: Clinical evaluation and skin surface digital profilometry analysis". Journal of Plastic, Reconstructive & Aesthetic Surgery. 70 (8): 1118–1128. doi:10.1016/j.bjps.2017.04.002. PMID 28526633. 14. ^ "UpToDate". www.uptodate.com. Retrieved 2018-04-14. ## External links[edit] * https://web.archive.org/web/20110910163035/http://www.biotopix.eu/pdf/W8.pdf * http://www.dermatology.ca/photoaging/ * https://www.isdin.com/en-US/blog/skincare/anti-aging/what-is-photoaging-and-why-do-we-have-to-care-about-it/ * http://911skin.com/uvbubarays.html * https://web.archive.org/web/20150209040004/http://www.skincarephysicians.com/agingskinnet/basicfacts.html * 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]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Photoaging	c0263415	29,180	wikipedia	https://en.wikipedia.org/wiki/Photoaging	2021-01-18T19:08:07	{"umls": ["C0263415"], "icd-10": ["L57"], "wikidata": ["Q3705873"]}
Angiomyolipoma Angiomyolipoma in both kidneys (arrows) in computer tomography. The tumours are hypodense (dark) due to fat content SpecialtyOncology Angiomyolipomas are the most common benign tumour of the kidney. Although regarded as benign, angiomyolipomas may grow such that kidney function is impaired or the blood vessels may dilate and burst, leading to bleeding. Angiomyolipomas are strongly associated with the genetic disease tuberous sclerosis, in which most individuals have several angiomyolipomas affecting both kidneys. They are also commonly found in women with the rare lung disease lymphangioleiomyomatosis. Angiomyolipomas are less commonly found in the liver and rarely in other organs. Whether associated with these diseases or sporadic, angiomyolipomas are caused by mutations in either the TSC1 or TSC2 genes, which govern cell growth and proliferation. They are composed of blood vessels, smooth muscle cells, and fat cells. Large angiomyolipoma can be treated with embolisation. Drug therapy for angiomyolipoma is at the research stage. The Tuberous Sclerosis Alliance has published guidelines on diagnosis, surveillance, and management.[1] ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 3 Diagnosis * 4 Treatment * 4.1 Follow-up * 5 Prognosis * 6 Epidemiology * 7 References * 8 External links ## Signs and symptoms[edit] Angiomyolipoma seen as a hyperechoic mass in the upper pole of an adult kidney on renal ultrasonography. Renal ultrasonography of a person with tuberous sclerosis and multiple angiomyolipomas in the kidney: Measurement of kidney length on the US image is illustrated by ‘+’ and a dashed line. CT scan of a renal angiomyolipoma. It involves the renal cortex, and has an attenuation of less than 20 HU on the Hounsfield scale, which are typical characteristics.[2] If the dilated blood vessels in an angiomyolipoma rupture, the resulting retroperitoneal haemorrhage causes sudden pain, accompanied with nausea and vomiting. When the patient presents in the emergency department, up to 20% are in shock.[3] ## Pathophysiology[edit] Myoid cells with clear cytoplasm spinning off of large vessels in a background of mature fat, the classic microscopic features of angiomyolipoma Angiomyolipomas are tumours consisting of perivascular epithelioid cells (cells which are found surrounding blood vessels and which resemble epithelial cells). A tumour of this kind is known as a PEComa, from the initials of perivascular epithelioid cell. Older literature may classify them as hamartomas (benign tumours consisting of cells in their correct location, but forming a disorganised mass) or choristoma (benign tumours consisting of normal cells in the wrong location). PEComas are themselves a kind of mesenchymal tumour which involves cells that form the connective tissue, cardiovascular, and lymphatic systems.[3] An angiomyolipoma is composed of varying proportions of vascular cells, immature smooth muscle cells, and fat cells.[3] These three components respectively give rise to the components of the name: angio-, myo-, and lip-. The -oma suffix indicates a tumour. Angiomyolipomas are typically found in the kidney, but have also been commonly found in the liver and less commonly the ovary, fallopian tube, spermatic cord, palate, and colon. The Maclean imaging classification system for renal angiomyolipomas is based on the location of the angiomyolipoma within the kidney.[4] Since all three components of an angiomyolipoma (vascular cells, immature smooth muscle cells, and fat cells) contain a "second-hit" mutation, they are believed to have derived from a common progenitor cell that suffered the common second-hit mutation.[3] ## Diagnosis[edit] Three methods of scanning can detect angiomyolipoma: ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI). Ultrasound is standard and is particularly sensitive to the fat in angiomyolipoma, but less so to the solid components. However, accurate measurements are hard to make with ultrasound, particularly if the angiomyolipoma is near the surface of the kidney (grade III).[4] CT is very detailed and fast, and allows accurate measurement. However, it exposes the patient to radiation and the dangers that a contrast dye used to aid the scanning may itself harm the kidneys. MRI is safer than CT, but many patients (particularly those with the learning difficulties or behavioural problems found in tuberous sclerosis) require sedation or general anaesthesia, and the scan cannot be performed quickly.[3] Some other kidney tumours contain fat, so the presence of fat is not diagnostic. Distinguishing a fat-poor angiomyolipoma from a renal cell carcinoma (RCC) can be difficult.[5] Both minimal fat AMLs and 80% of the clear-cell type of RCCs display signal drop on an out-of-phase MRI sequence compared to in-phase.[6] Thus, a lesion growing at greater than 5 mm per year may warrant a biopsy for diagnosis.[3] Incidental discovery of angiomyolipomas should trigger consideration of tuberous sclerosis complex (TSC) and lymphangioleiomyomatosis, especially if they are large, bilateral, and/or multiple. Screening for TSC includes a detailed physical exam, including dermatologic and ophthalmologic evaluations, by TSC expert clinicians and a CT or MRI of the brain. Screening for LAM includes a high-resolution CT of the lung and pulmonary function testing. ## Treatment[edit] Everolimus is FDA approved for the treatment of angiomyolipomas. Treatment should be considered for asymptomatic, growing AMLs measuring larger than 3 cm in diameter.[1] Angiomyolipomas do not normally require surgery unless life-threatening bleeding is present.[5] Some centres may perform preventative selective embolisation of the angiomyolipoma if it is more than 4 cm in diameter, due to the risk of haemorrhage.[7] People with tuberous sclerosis are advised to have yearly renal scans, though patients with very stable lesions could be monitored less frequently. The research in this area is lacking. Even if no angiomyolipoma is found, one can develop at any life stage. The angiomyolipoma can grow rapidly.[3] In tuberous sclerosis, typically, many angiomyolipomas affect each kidney. Not uncommonly, more than one intervention may be required during lifetime. Since kidney function may already be impaired (up to half the kidney may be lost before function loss is detectable), preserving as much kidney as possible is vital when removing any lesion. Large angiomyolipomas are treated by embolization, which reduces the risk of haemorrhage and can also shrink the lesion. A side effect of this treatment is postembolisation syndrome, severe pain and fever, but this is easily managed and lasts only a few days.[3] A ruptured aneurysm in an angiomyolipoma leads to blood loss that must be stopped (though embolisation) and compensated for (through intravenous fluid replacement). Therefore, removal of the affected kidney (nephrectomy) is strongly discouraged, though may occur if the emergency department is not knowledgeable about tuberous sclerosis.[3] Embolisation involves inserting a catheter along the blood vessels to the tumour. The blood vessels are then blocked, typically by injecting ethanol or inert particles. The procedure can be very painful, so analgesics are used. The destroyed kidney tissue often causes postembolisation syndrome, which manifests as nausea, vomiting, fever, and abdominal pain, and lasts a few days. Embolisation (in general) has an 8% rate of morbidity and a 2.5% rate of mortality, so is not considered lightly.[7] Patients with kidney loss should be monitored for hypertension (and treated for it if discovered) and avoid nephrotoxic drugs such as certain pain relievers and intravenous contrast agents. Such patients who are unable to communicate effectively (due to age or intellectual disability) are at risk of dehydration. Where multiple or large angiomyolipomas have caused chronic kidney disease, dialysis is required.[3] Robotic assisted partial nephrectomy has been proposed as a surgical treatment of a ruptured angiomyolipoma combining the advantages both of a kidney preservation procedure and the benefits of a minimal invasive procedure without compromising the safety of the patient.[8] ### Follow-up[edit] It is suggested that no follow-up is needed for angiomyolipoma-like incidental imaging findings measuring less than 1 or 2 cm.[9][10] Alternatively, a renal ultrasonography every 3 or 4 years has been suggested for angiomyolipoma-like masses measuring less than 2 cm.[11] For those measuring 2 to 4 cm, annual ultrasonography is recommended.[11] Those over 4 cm are usually surgically removed, but for those that are not, it is recommended to perform an ultrasonography after 6 months, and then annually if stable.[11] ## Prognosis[edit] Small angiomyolipomas and those without dilated blood vessels (aneurysms) cause few problems, but angiomyolipomas have been known to grow as rapidly as 4 cm in one year. Angiomyolipomas larger than 5 cm and those containing an aneurysm pose a significant risk of rupture, which is a medical emergency, as it is potentially life-threatening. One population study found the cumulative risk of haemorrhage to be 10% in males and 20% in females.[3] A second problem occurs when the renal angiomyolipomas take over so much kidney that the function is impaired, leading to chronic kidney disease. This may be severe enough to require dialysis. A population survey of patients with TSC and normal intelligence found 1% were on dialysis.[3] ## Epidemiology[edit] Histopathologic types of kidney tumor, with relative incidences and prognoses. Angiomyolipoma is seen at right in pie chart. Angiomyolipomas are the most common benign tumour of the kidney, and are found either in patients with tuberous sclerosis or sporadically. About 80–90% of cases are sporadic, and these are most commonly found in middle-aged women.[5] In patients with TSC, a longitudinal study found 80% will have some form of renal lesion by around 10 years of age. Of these, 75% are angiomyolipomas and 17% are cysts. The angiomyolipomas increased in size in around 60% of these children. An autopsy study and TSC clinic survey found a prevalence of 67 and 85%, respectively, for patients with TSC. Both genders are affected equally.[3] ## References[edit] 1. ^ a b Northrup, H; Krueger, DA (2013). "International Tuberous Sclerosis Complex Consensus Group. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference". Pediatr Neurol. 49 (4): 243–254. doi:10.1016/j.pediatrneurol.2013.08.001. PMC 4080684. PMID 24053982. 2. ^ Dr Yuranga Weerakkody and Dr Behrang Amini. "Renal angiomyolipoma". Radiopaedia. Retrieved 2019-08-02. 3. ^ a b c d e f g h i j k l m Bissler JJ, Henske EP. Renal Manifestations of Tuberous Sclerosis Complex. In: Kwiatkowski DJ, Wiittlemore DJ, Thiele EA, editors. Tuberous Sclerosis Complex: Genes, Clinical Features and Therapeutics. Wiley-VCH Verlag GmbH; 2010. p. 321–325. ISBN 3-527-32201-9. 4. ^ a b D. F. W. Maclean, R. Sultana, R. Radwan, L. McKnight, and J. Khastgir, Is the follow-up of small renal angiomyolipomas a necessary precaution? Clinical Radiology, vol.69, no.8, pp.822–826, 2014 5. ^ a b c Shin, NY; Kim, MJ; Chung, JJ; Chung, YE; Choi, JY; Park, YN (May–Jun 2010). "The differential imaging features of fat-containing tumors in the peritoneal cavity and retroperitoneum: the radiologic-pathologic correlation" (PDF). Korean Journal of Radiology. 11 (3): 333–45. doi:10.3348/kjr.2010.11.3.333. PMC 2864861. PMID 20461188. 6. ^ Rinze Reinhard, Mandy van der Zon-Conijn and Robin Smithuis. "Kidney - Solid masses". Radiology Assistant. Retrieved 2017-10-27. 7. ^ a b Loffroy, R; Rao, P; Kwak, BK; Ota, S; De Lin, M; Liapi, E; Geschwind, JF (May–Jun 2010). "Transcatheter arterial embolization in patients with kidney diseases: an overview of the technical aspects and clinical indications" (PDF). Korean Journal of Radiology. 11 (3): 257–68. doi:10.3348/kjr.2010.11.3.257. PMC 2864852. PMID 20461179. 8. ^ Ploumidis, A; Katafigiotis, I; Thanou, M; Bodozoglou, N; Athanasiou, L; Ploumidis, A (2013). "Spontaneous Retroperitoneal Hemorrhage (Wunderlich Syndrome) due to Large Upper Pole Renal Angiomyolipoma: Does Robotic-Assisted Laparoscopic Partial Nephrectomy Have a Role in Primary Treatment?". Case Reports in Urology. 2013: 498694. doi:10.1155/2013/498694. PMC 3784227. PMID 24106637. 9. ^ Doshi, Ankur M.; Ayoola, Abimbola; Rosenkrantz, Andrew B. (2017). "Do Incidental Hyperechoic Renal Lesions Measuring Up to 1 cm Warrant Further Imaging? Outcomes of 161 Lesions". American Journal of Roentgenology. 209 (2): 346–350. doi:10.2214/AJR.16.17490. ISSN 0361-803X. 10. ^ Maclean, D.F.W.; Sultana, R.; Radwan, R.; McKnight, L.; Khastgir, J. (2014). "Is the follow-up of small renal angiomyolipomas a necessary precaution?". Clinical Radiology. 69 (8): 822–826. doi:10.1016/j.crad.2014.03.016. ISSN 0009-9260. 11. ^ a b c Vicente E Torres, York Pei. "UpToDate". UpToDate. This topic last updated: Dec 30, 2017. ## External links[edit] Classification D * ICD-10: D30.0 * ICD-9-CM: 223.0 * ICD-O: M8860/0 * MeSH: D018207 * DiseasesDB: 29496 * SNOMED CT: 19929002 * 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 * 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]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Angiomyolipoma	c0206633	29,181	wikipedia	https://en.wikipedia.org/wiki/Angiomyolipoma	2021-01-18T19:07:33	{"gard": ["12024"], "mesh": ["D018207"], "umls": ["C0206633"], "icd-9": ["223.0"], "icd-10": ["D30.0"], "wikidata": ["Q539681"]}
Equine protozoal myeloencephalitis in various stages Equine protozoal myeloencephalitis (EPM), is a disease caused by the apicomplexan parasite Sarcocystis neurona[1] that affects the central nervous system of horses. ## Contents * 1 History * 2 Causes * 3 Symptoms * 4 Treatment and prevention * 5 References * 5.1 Bibliography * 6 External links ## History[edit] EPM was first discovered in the 1960s by the American biologist Dr. Jim Rooney.[2] The disease is considered rare, though recently, an increasing number of cases have been reported.[citation needed] Previous research identified the "barn cat" as the definitive host of the disease. However, since that time it has been learned that the definitive host is the opossum, while any of a number of mammals can serve as intermediate hosts in the disease's two-host life-cycle. Those with horses should not panic and kill opossums or wildlife rather keep feed covered and stalls clean.[3] The term EPM refers to the clinical neurologic symptoms caused by the parasite, not infection itself. The majority of horses infected with S. neurona do not exhibit neurologic symptoms consistent with EPM. There are six subspecies of S. neurona which can be identified by surface antigens (SAG). Equine EPM is caused by the parasites that exhibit SAG1, SAG5, and SAG6. SAG1 and SAG5 are responsible for the majority of EPM cases in horses.[4] Horses produce antibodies to these surface antigens. Serum antibody testing is available that measures levels of these antibodies in the blood of horses, which is helpful in diagnosing EPM in an ataxic horse. Serial blood levels are helpful in guiding treatment. In experimentally infected horses it takes 14 days from infection to positive antibody tests.[5] 80% of horses with EPM have positive antibody tests. A negative antibody test in the presence of EPM results if testing is done before 17 days or if the horse has been treated with antiprotozoal drugs which delays antibody production. ## Causes[edit] Life cycle of S. neurona EPM is caused by the parasite Sarcocystis neurona. The life cycle of S. neurona is well described. In order to complete its life cycle this parasite needs two hosts, a definitive and an intermediate. In the laboratory, raccoons, cats, armadillos, skunks, and sea otters have been shown to be intermediate hosts. The opossum is the definitive host of the disease, passing the parasite through feces. Horses contract EPM from contaminated feed or water. Horses cannot pass the disease among themselves; that is, one horse cannot contract the disease from another infected horse. The horse is a dead-end, or aberrant, host of the parasite.[6] ## Symptoms[edit] The most common symptoms of EPM are ataxia, general weakness with muscle spasticity. However this is not specific to EPM and is common to many other neurological disorders. Clinical signs among horses with EPM include a wide array of symptoms that may result from primary or secondary problems. Some of the signs are difficult to distinguish from other problems, such as lameness, which can be attributed to many different causes. Apparent lameness, particularly atypical lameness or slight gait asymmetry of the rear limbs are commonly caused by EPM. Focal muscle atrophy, or even generalized muscle atrophy or loss of condition may result. Secondary signs also occur with neurologic disease. Airway abnormalities, such as laryngeal hemiplegia, snoring, or airway noise of undetermined origin may result from damage to the nerves which control the throat, although this is quite uncommon. In experimentally infected horses, very early signs included loss of appetite, decreased tongue tone, facial paresis, altered mental status, generalized weakness, and lameness. It is thought that Sarcocystis neurona does not need to enter the CNS to cause disease, in some cases S. neurona has been found in the CNS but usually not. In cases where S. neurona is found in the CNS, white blood cells probably play a role in the parasite's penetration of the blood brain barrier. ## Treatment and prevention[edit] EPM is treatable, but irreversible damage to the nervous system is possible. It is important to identify the disease as early as possible and begin treatment with antiprotozoal drugs. There are currently three FDA approved treatments available in the US: ReBalance (sulfadiazine and pyrimethamine),[7][8] Marquis (ponazuril),[9] and Protazil (diclazuril). These drugs minimize the infection but do not kill the parasite. The use of anti-inflammatory agents such as Banamine, corticosteroids, or phenylbutazone are often used to help reduce inflammation and limit further damage to the CNS. Antioxidants, such as vitamin E may help promote the restoration of nervous tissue. Response to treatment is often variable, and treatment may be expensive. Recently, antiprotozoal treatments that kill the parasite and clear the infection have shown promise.[10] The inflammatory component is thought responsible for the symptoms of EPM; anti inflammatory drugs that target the IL-6 pathway have been particularly effective at reversing symptoms. Control of this disease includes proper storage of hay and feed, the control of "barn cats" on the property, and prompt disposal of animal carcasses. No vaccine is available. ## References[edit] 1. ^ Dubey, J. P.; Davis, S. W.; Speer, C. A.; Bowman, D. D.; de Lahunta, A.; Granstrom, D. E.; Topper, M. J.; Hamir, A. N.; Cummings, J. F.; Suter, M. M. (April 1991). "Sarcocystis neurona n. sp. (Protozoa: Apicomplexa), the Etiologic Agent of Equine Protozoal Myeloencephalitis" (Submitted manuscript). The Journal of Parasitology. 77 (2): 212–8. doi:10.2307/3283084. JSTOR 3283084. PMID 1901359. 2. ^ Rooney, J. R.; Prickett, M. E.; Delaney, F. M.; Crowe, M. W. (1970-07-01). "Focal myelitis-encephalitis in horses". The Cornell Veterinarian. 60 (3): 494–501. ISSN 0010-8901. PMID 5464755. 3. ^ Reed, S.M.; Furr, M.; Howe, D.K.; Johnson, A.L.; MacKay, R.J.; Morrow, J.K.; Pusterla, N.; Witonsky, S. (March 2016). "Equine Protozoal Myeloencephalitis: An Updated Consensus Statement with a Focus on Parasite Biology, Diagnosis, Treatment, and Prevention". Journal of Veterinary Internal Medicine. 30 (2): 491–502. doi:10.1111/jvim.13834. PMC 4913613. PMID 26857902. 4. ^ Crowdus, Carolyn A.; Marsh, Antoinette E.; Saville, William J.; Lindsay, David S.; Dubey, J.P.; Granstrom, David E.; Howe, Daniel K. (November 2008). "SnSAG5 is an alternative surface antigen of Sarcocystis neurona strains that is mutually exclusive to SnSAG1". Veterinary Parasitology. 158 (1–2): 36–43. doi:10.1016/j.vetpar.2008.08.012. PMID 18829171. 5. ^ Sofaly, C. D.; Reed, S. M.; Gordon, J. C.; Dubey, J. P.; Oglesbee, M. J.; Njoku, C. J.; Grover, D. L.; Saville, W. J. A. (December 2002). "Experimental Induction of Equine Protozoan Myeloencephalitis (EPM) in the Horse: Effect of Sarcocystis neurona Sporocyst Inoculation Dose on the Development of Clinical Neurologic Disease". The Journal of Parasitology. 88 (6): 1164–70. doi:10.2307/3285489. JSTOR 3285489. PMID 12537112. 6. ^ "Equine Protozoal Myeloencephalitis: Introduction". The Merck Veterinary Manual. 2006. Retrieved 2007-07-03. 7. ^ "ReBalance® sulfadiazine/pyrimethamine oral suspension for horses". Prnpharmacal.com. Retrieved 2019-09-29. 8. ^ "Freedom of information summary: NADA 141-240, REBALANCE Antiprotozoal Oral Suspension" (PDF). FDA. Retrieved 16 July 2016. 9. ^ Furr, M.; McKenzie, H.; Saville, W. J A.; Dubey, J. P.; Reed, S. M.; Davis, W. (June 2006). "Prophylactic administration of ponazuril reduces clinical signs and delays seroconversion in horses challenged with Sarcocystis neurona". Journal of Parasitology. 92 (3): 637–643. doi:10.1645/0022-3395(2006)92[637:PAOPRC]2.0.CO;2. 10. ^ Ellison, Siobhan P.; Lindsay, David S. (2012). "Decoquinate combined with levamisole reduce the clinical signs and serum SAG 1, 5, 6 antibodies in horses with suspected equine protozoal myeloencephalitis" (PDF). The International Journal of Applied Research in Veterinary Medicine. 10 (1): 1–7. ### Bibliography[edit] Cutler T, MacKay RJ, Ginn PE, et al. Are Sarcocystis neurona and Sarcocystis falcatula synonymous? A horse infection challenge. J. Parasitol. 85:301-305, 1999. Fenger CK, Granstrom DE, Gajadhar A, et al. Experimental induction of equine protozoal myeloencephalitis in horses using Sarcocystis sp. sporocysts from the opossum (Didelphis virginiana). Vet Parasitol 68:199-213, 1997. MacKay RJ. Serum antibodies to Sarcocystis neurona-half the horses in the United States have them! JAVMA 210:482-483, 1997. Granstrom DE. Diagnosis of equine protozoal myeloencephalitis: Western blot analysis. Proc Am Coll Vet Intern Med Forum 587–590, 1993. Granstrom DE, MacPherson JM, Gajadhar AA, et al. Differentiation of Sarcocystis neurona from eight related coccidia by random amplified polymorphic NA assay. J Molec Cellular Probes 8:353-356, 1994. Hamir AN, Moser G, Galligan DT, et al. Immunohistochemical study to demonstrate Sarcocystis neurona in equine protozoal myeloencephalitis. J Vet Diagn Invest 5:418-422, 1993. Furr M, MacKay R, Granstrom D, et al. J Vet Intern Med 16: 618–621, 2002. Ellison SP, Omara-Opyeme AL, Yowell C, Dame J. Molecular characterization of a major 29 kDa surface antigen of Sarcocystis neurona. J Parasit 32:217-225, 2002. Andrews FM. A review: Determining the sensitivity and specificity of western blot tests for diagnosis of Equine protozoal myeloencephalitis. Equine Med Rev 2003.11. Ellison SP. Development of a recombinant protein for the identification of S. neurona infections in horses. [PhD dissertation]. University of Florida, Gainesville, Florida, 2001. Amery, W K P and Bruynseels, J M. Levamisole, the story and the lessons. 1992, Inr. J Immunopharmac, 14(3):481 doi: 481–86 10.1016/0192-0561(92)90179-O Sajid, M S. Immunomodulation effects of various anti-parasitics:a review. 2006, Parasitol, Vol. 132, pp. 301–13 Lindsay, David A. David Lindsay Decoquinate,4-hydroxyquinalones and hydroxyquinalones and napthoquinones for the prevention and treatment of equine protozoal myeloencephalitis caused by Sarcocystis neurona. 2001. Ellison, Siobhan P. sarcocystis. Pathogenes Inc.[Online] Pathogenes Inc, 2003 Limited genetic diversity among Sarcocystis neurona strains infecting southern sea otters precludes distinction between marine and terrestrial isolates. Wendte JM, Miller MA, Nandra AK, Peat SM, Crosbie PR, Conrad PA, Grigg ME. 1–2, Apr 2010, Vet Parasitol, Vol. 169, pp. 37–44 Development of an ELISA to detect antibodies torSAG 1 in the horse. S P Ellison, T Kennedy, KK Brown. 4, 2003, J App Res Vet Med, Vol. 1, pp. 318–327 Experimental infection of horses with S. neurona merozoites as a model for Equine Protozoal Myeloencephalitis. Ellison, S. P., Greiner, E., Brown, K K., Kennedy, T. 2, 2004, J App Res Vet Med, Vol.2, pp. 79–89. Characterization of a Sarcocystis neurona isolate from a Missouri horse with equine protozoal myeloencephalitis. Marsh AE, Johnson PJ, Ramos-Vara J, Johnson GC. 2–4, Feb 2001, Vet Parasitol, Vol. 95, pp. 143–54. Cytokine Gene Expression in Response to SnSAG1in Horses with Equine Protozoal Myeloencephalitis. Spencer JA, Deinnocentes P, Moyana EM, Guarino AJ, Ellison SP, Bird RC, and BlagburnBL. 2004, J. Parasitol. Immune response to Sarcocystis neurona infectionin naturally infected horses with equine protozoal myeloencephalitis. Yang J., Ellison S., GogalR., Norton H., Lindsay D S., Andrews R., WardR., Ward D., Witonsky. 3–4, 2006, Vol. 138, pp. 200–10. In vitro suppressed immune response in horses experimentally infected with Sarcocystis neurona. Witonsky S., Ellison S., Yang J., Gogal R., NortonH., Yasuhiro S., Sriranganathan N., Andrews F., Ward D., Lindsay DS. 1, 2008, Vol. 12, p. 1. Antibody index and specific antibody quotient inhorses after intragastric administration of Sarcocystis neurona sporocysts. Heskett KA, Mackay RJ. 3, Mar 2008, Am J Vet, Vol. 69, pp. 403–9. An equine protozoal myeloencephalitis challenge model testing a second transport after inoculation with Sarcocystis neurona sporocysts. Saville WJ, Sofaly CD, Reed SM, Dubey JP, Oglesbee MJ, Lacombe VA, Keene RO, Gugisberg KM, Swensen SW, Shipley RD, Chiang YW, Chu HJ, Ng T. 6,2006, J Parasitol, Vol. 90, pp. 1406–10. ## External links[edit] * Report [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Equine protozoal myeloencephalitis	None	29,182	wikipedia	https://en.wikipedia.org/wiki/Equine_protozoal_myeloencephalitis	2021-01-18T18:46:57	{"wikidata": ["Q5384512"]}
Psychoorganic syndrome (POS), also known as organic psychosyndrome, is a progressive disease comparable to presenile dementia. It consists of psychopathological complex of symptoms that are caused by organic brain disorders that involve a reduction in memory and intellect. Psychoorganic syndrome is often accompanied by asthenia. Psychoorganic syndrome occurs during atrophy of the brain, most commonly during presenile and senile age (e.g. Alzheimer's disease, senile dementia). There are many causes, including cerebrovascular diseases, CNS damages to traumatic brain injury, intoxication, exposure to organic solvents such as toluene, chronic metabolic disorders, tumors and abscesses of the brain, encephalitis, and can also be found in cases of diseases accompanied by convulsive seizures. Psychoorganic syndrome may occur at any age but is most pronounced in elderly and senile age. Depending on the nosological entity, the main symptoms of psychoorganic syndrome are expressed differently. For example, in atrophic cases such as Alzheimer's disease, the symptoms are more geared towards a memory disorder, while in Pick's disease, mental disorders are more commonly expressed. ## Contents * 1 Symptoms * 2 Cause * 3 Mechanism * 4 Diagnosis * 4.1 Various symptom diagnosis * 5 Treatment * 6 History * 7 Recent research * 8 See also * 9 References ## Symptoms[edit] Patients with psychoorganic syndrome often complain about headaches, dizziness, unsteadiness when walking, poor tolerance to the heat, stuffiness, atmospheric pressure changes, loud sounds, neurological symptoms. The common reported psychological symptoms include:[1][2][3] * loss of memory and concentration * emotional liability * Clinical fatigue * long term major depression * severe anxiety * reduced intellectual ability The cognitive and behavioral symptoms are chronic and have little response to treatment.[2] Depending on lesion location, some patients may experience visual complications.[3] ## Cause[edit] Psycho-organic syndrome is typically diagnosed in individuals following 5–10 years of consistent exposure to chemicals like xylene, toluene, and styrene, which are generally found in paint, plastic and degreasing products.[1] Patients work and environmental history must be evaluated for exposure to organic chemicals. A traumatic brain injury may also lead to POS.[3] Consistent intoxication (ie excess use of alcohol and drugs) may also cause a lesion in the brain, eventually leading to POS.[3] Lyme disease, the great "new imitator", has been known to mimick depression, schizophrenia, depersonalization disorder, and obsessive-compulsive disorder. Although the cause varies by each individual case, localization of the atrophy in the brain can occur due to aging and without external causes.[4] Prevention includes proper and regular use of Preventive Personal Equipment (PPE) in work environments that involve organic chemicals and limiting alcohol and drug substance intake. ## Mechanism[edit] Psychoorganic syndrome is a combination of various symptoms that are caused by organic changes in the brain.[5] The exact component of the solvents that causes the neurological disorder is difficult to isolate due to worker generally being exposed to mixtures of various grades, compositions, and purity of solvents.[6] At the initial stage, asthenia is prevalent and the progress of the disorder is slow. Acute onset can be diagnosed when a large amount of psychological symptoms surface. The final stage of the disorder is made up of numerous disorders, including dementia, Korsakov's syndrome, and includes severe personality change such as depression, anxiety, memory loss, and drastic change in intellect. Level of kindness, happiness, and insight are greatly affect in the final stage.[5] The disorder stems from a defect in brain tissue, usually atrophy from another neurological disorder.[4] > "In pathological findings, focal or diffuse signs of atrophy without inflammation or severe vascular insufficiency are present. Basic clinical picture depends on the localization of atrophy in brain."[4] Although the exact mechanism that solvents have on the nervous system are not fully understood, the metabolism of the solvents in the body that turn them into toxic intermediates are important. Some evidence shows that genetic polymorphisms affect the activity of metabolic enzymes that metabolize foreign chemicals.[6] ## Diagnosis[edit] Along with occupational and environmental evaluation, a neurological exam, ECHO, EEG, CT-San, and X-ray of the brain may be conducted to determine disorder.[1][3] Neuroimaging that detects cerebral atrophy or cardiovascular subcortical alterations can help point to psychoorganic syndrome. Strong CNS lesions are detected in POS patients.[7] However, this is found to be difficult as many psychiatric disorders, like dementia, have common diagnosis.[2] Diagnosing POS is an ongoing and developing in the medical and psychiatric industry. Exact diagnosis is difficult due to many symptoms mirroring other psychological disorders in the older aged patients. ### Various symptom diagnosis[edit] CT scan or MRI can confirm dementia via observation of ventricular dilation and cortical substance degeneration.[4] Pick's disease can be confirmed via CT scan or MRI with atrophy of frontal and temporal lobe roots.[4] Alzheimer's is a disease confirmed by atrophy of the parietal and temporal lobe ganglia along with changes in the cortical ganglia found in a CT scan or MRI.[4] ## Treatment[edit] In a confirmed medical diagnosis, therapy is used to isolate and begin treating the cause of the disorder. Thereafter, psychiatric medication is used a secondary step in treatment. Medications include antipsychotic, antidepressant, or sedation-inducing, varying on the patients severity.[8] Treatment of psychoorganic syndrome is directed at the main disease. Nootropics like piracetam, have had positive effects on patients[citation needed]. Vitamin therapy, antioxidants, neurotropic, and cerebroprotective have also found to be effective when put on a repeat course[citation needed]. ## History[edit] [9] POS was suggested to be associated with long term and high level solvent exposure in early studies conducted in Scandinavia. These studies found neurological deficits such as personality changes and memory loss were tied to these exposures. However, these studies were highly criticized and found biased, causing doubt in the existence of the syndrome. Furthermore, various health organizations had difficulty coming to an agreement on the definition of the syndrome. In 1985, the syndrome was defined and provided clear criteria that could be used by patients and medical professionals to help identify the syndrome and isolate ways of prevention. ## Recent research[edit] In a 2007 clinical study conducted in Sweden on 128 subjects who had constant high exposure to solvents in their work environments, a definite link to POS was unable to be determined. However, the subject who had diagnosis of POS showed increased neurological symptoms with increased brain atrophy in as little as 3 years of exposure.[10] ## See also[edit] * Neurotoxicity ## References[edit] 1. ^ a b c "psycho-organic syndrome". TheFreeDictionary.com. Retrieved 2015-11-02. 2. ^ a b c "Does the psycho-organic syndrome exist?". www.researchgate.net. Retrieved 2015-11-02. 3. ^ a b c d e "The main symptoms of psycho-organic syndrome". medical-notes-help.com. Archived from the original on 2015-12-22. Retrieved 2015-11-02. 4. ^ a b c d e f "PEOI General psychopathology". www.peoi.org. Retrieved 2015-11-03. 5. ^ a b "Organic brain diseases". www.peoi.org. Retrieved 2015-11-03. 6. ^ a b Dick, F D (2006-03-01). "Solvent neurotoxicity". Occupational and Environmental Medicine. 63 (3): 221–226. doi:10.1136/oem.2005.022400. ISSN 1351-0711. PMC 2078137. PMID 16497867. 7. ^ Möller, C.; Odkvist, L. M.; Thell, J.; Larsby, B.; Hydén, D.; Bergholtz, L. M.; Tham, R. (1989-02-01). "Otoneurological findings in psycho-organic syndrome caused by industrial solvent exposure". Acta Oto-Laryngologica. 107 (1–2): 5–12. doi:10.3109/00016488909127473. ISSN 0001-6489. PMID 2784610. 8. ^ Thomas, C.; Driessen, M.; Arolt, V. (2010-05-01). "[Diagnostic work-up and treatment of acute psycho-organic syndrome]". Der Nervenarzt. 81 (5): 613–628, quiz 629–630. doi:10.1007/s00115-010-3013-9. ISSN 1433-0407. PMC 7095979. PMID 20454878. 9. ^ Dick, F D (2006-03-01). "Solvent neurotoxicity". Occupational and Environmental Medicine. 63 (3): 221–226. doi:10.1136/oem.2005.022400. ISSN 1351-0711. PMC 2078137. PMID 16497867. 10. ^ Flodin, Ulf; Edling, Christer; Axelson, Olav (1984-01-01). "Clinical studies of psychoorganic syndromes among workers with exposure to solvents". American Journal of Industrial Medicine. 5 (4): 287–295. doi:10.1002/ajim.4700050405. ISSN 1097-0274. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Psychoorganic syndrome	c4285867	29,183	wikipedia	https://en.wikipedia.org/wiki/Psychoorganic_syndrome	2021-01-18T18:33:46	{"icd-9": ["310.8", "293.1", "310.1"], "icd-10": ["F07.9"], "wikidata": ["Q7256456"]}
For a phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000. Mapping Finckh et al. (1998) collected DNA samples from 20 large consanguineous Indian families in which autosomal recessive retinitis pigmentosa (arRP) segregated and that were suitable for homozygosity mapping of the disease locus. After excluding linkage to all known arRP loci, a genomewide scan was initiated. In 2 families, homozygosity mapping, haplotype analysis, and linkage data mapped the disease locus (RP22) in an approximately 16-cM region between D16S287 and D16S420 on the proximal short arm of chromosome 16. The location of RP22 was given as 16p12.3-p12.1. Molecular Genetics By direct sequencing, Finckh et al. (1998) found no mutation in the CRYM gene (123740), which encodes mu crystallin and maps to the same region. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	RETINITIS PIGMENTOSA 22	c0035334	29,184	omim	https://www.omim.org/entry/602594	2019-09-22T16:13:35	{"doid": ["0110400"], "mesh": ["D012174"], "omim": ["602594"], "orphanet": ["791"]}
## Summary ### Clinical characteristics. Mucolipidosis III gamma (ML IIIγ) is a slowly progressive inborn error of metabolism mainly affecting skeletal, joint, and connective tissues. Clinical onset is in early childhood; the progressive course results in severe functional impairment and significant morbidity from chronic pain. Cardiorespiratory complications (restrictive lung disease from thoracic involvement, and thickening and insufficiency of the mitral and aortic valves) are rarely clinically significant. A few (probably <10%) affected individuals display mild cognitive impairment. ### Diagnosis/testing. The diagnosis of ML IIIγ is established in a proband with suggestive clinical and radiographic findings and biallelic pathogenic variants in GNPTG identified on molecular genetic testing. ### Management. Treatment of manifestations: No measures are known to be effective in treating the progressive limitation of motion in large and small joints. Low-impact physical therapy is usually well tolerated. In older adolescents and adults joint replacement has been successful in relieving hip pain and knee pain. Carpal tunnel signs, and rarely tarsal tunnel symptoms, may require surgical tendon release procedures for temporary relief. Later in the disease course when bone pain of variable intensity may become frequent, management focuses on pain relief. Bisphosphonate treatment in patients with significant skeletal disease and markedly decreased bone mineral densitometry can be considered. When significant cardiac valvular dysfunction disrupts ventricular function, valve replacement needs to be considered. Addressing the social and emotional needs of patients and their families is recommended. Surveillance: Yearly outpatient clinic visits (unless more frequent pain, cardiac, and/or respiratory monitoring is warranted) to assess pain level, musculoskeletal needs, gross motor and fine motor function, vision, cardiac and respiratory function, development, educational needs, psychological issues, and utilization of community resources. Frequency of DEXA scans depends on age and results of prior studies. Agents/circumstances to avoid: Vigorous stretching exercises because they are ineffective, painful, and may damage the surrounding joint capsule and adjacent tendons. ### Genetic counseling. ML IIIγ is inherited in an autosomal recessive manner. If both parents are known to be carriers of one GNPTG pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the GNPTG pathogenic variants in an affected family member are known, carrier testing for at-risk relatives, prenatal diagnosis for a pregnancy at increased risk, and preimplantation genetic testing are possible. ## Diagnosis Formal diagnostic criteria for mucolipidosis III gamma have not been established. ### Suggestive Findings Mucolipidosis III gamma (ML IIIγ) should be suspected in individuals with the following clinical and radiographic findings [Raas-Rothschild et al 2004, Tüysüz et al 2018, Nampoothiri et al 2019]. Clinical findings * Growth rate deceleration * Joint stiffness of the fingers, shoulders, and hips * Gradual mild coarsening of facial features * Genu valgum * Spinal deformities including scoliosis and hyperlordosis * No organomegaly Radiographic findings. In early childhood, skeletal radiographs reveal mild-to-moderate dysostosis multiplex: * Pelvis and hips. Hypoplastic iliac bones with flared iliac wings and shallow and irregular acetabula and moderate-to-severe dysplasia of the proximal femoral epiphyses – giving rise to coxa valga – are the most striking radiologic abnormalities. * Hands and feet. Diaphyses of metacarpals and phalanges are mildly shortened with "bullet-shaped" distal end of phalanges; carpal bones may be smaller than normal and with osteoporotic changes. * Ribs. Widening especially in the lateral and frontal costochondral junctions * Spine. Generalized platyspondyly; irregularity of the anterior upper and lower vertebral endplates; wedge-shaped and small ovoid vertebral bodies In late childhood or adolescence, the changes on skeletal radiographs worsen with the development of generalized osteopenia. ### Establishing the Diagnosis The diagnosis of ML IIIγ is established in a proband with suggestive clinical and radiographic findings and biallelic pathogenic variants in GNPTG identified on molecular genetic testing (see Table 1). #### Molecular Genetic Testing Approaches can include a combination of gene-targeted testing (multigene panel) and comprehensive genomic testing (exome sequencing, genome sequencing) depending on the phenotype. Gene-targeted testing (Option 1) requires that the clinician determine which gene(s) are likely involved, whereas genomic testing (Option 2) does not. Option 1. A mucolipidosis or lysosomal storage disorders multigene panel that includes GNPTG and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. Option 2. Comprehensive genomic testing. Exome sequencing is most commonly used; genome sequencing is also possible. If exome sequencing is not diagnostic, exome array (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by sequence analysis. For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. ### Table 1. Molecular Genetic Testing Used in Mucolipidosis III Gamma View in own window Gene 1MethodProportion of Pathogenic Variants 2 Detectable by Method 3 GNPTGSequence analysis 4~99%% 5 Gene-targeted deletion/duplication analysis 6None detected 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\. Data from Nampoothiri et al [2019], Velho et al [2019] 4\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 5\. Two intronic deletions reported are of a size detectable by sequencing but could be missed due to their location [Persichetti et al 2009]. 6\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. #### Supportive Biochemical Findings Activity of lysosomal hydrolases. In ML IIIγ the activity of nearly all lysosomal hydrolases is up to tenfold higher in serum dried blood and other body fluids (e.g., media from cultured fibroblasts or amniocytes) than in normal controls because mannose-6-phosphate, which is essential to proper targeting of lysosomal acid hydrolases to lysosomes, cannot be added adequately to the hydrolases and they are overexcreted into the extracellular space. The following lysosomal hydrolases are of most interest as their increased activity in serum and other body fluids is relevant in the differential diagnosis of ML III and lysosomal storage disorders: * β-D-hexosaminidase (EC 3.2.1.52) * β-D-glucuronidase (EC 3.2.1.31) * β-D-galactosidase (EC 3.2.1.23) * α-D-mannosidase (EC 3.2.1.24) Note: (1) The intracellular lysosomal hydrolase activity in cultured cells, such as skin fibroblasts, is low compared to control cells and permits support of the diagnosis as well. (2) ML IIIγ cannot be diagnosed by assay of acid hydrolases in leukocytes. (In ML II, specific activity of lysosomal enzymes is elevated in plasma, deficient in fibroblasts, and normal in leukocytes.) (3) Biochemical testing (measurement of lysosomal hydrolase activity) does not distinguish ML III alpha/beta from ML IIIγ. (4) Biochemical testing cannot be used to identify heterozygotes. UDP-N-acetylglucosamine: lysosomal hydrolase N-acetylglucosamine-1-phosphotransferase enzyme (also known as GlcNAc-phosphotransferase) (EC 2.7.8.17). Demonstration of deficiency of the enzyme GlcNAc-phosphotransferase, encoded by GNPTAB (causing GNPTAB-related disorders) and GNPTG (causing ML IIIγ), confirms the diagnosis of a GNPTAB-related disorder and ML IIIγ. ## Clinical Characteristics ### Clinical Description Mucolipidosis III gamma (ML IIIγ) is a slowly progressive inborn error of metabolism mainly affecting skeletal, joint, and connective tissues. Clinical onset is in early childhood and the progressive course, including mild cardiac involvement, results in severe functional impairment and significant morbidity. A few (probably <10%) affected individuals may display mild cognitive impairment [Nampoothiri et al 2019], but the majority do not. The initial manifestation in most affected individuals is joint stiffness in fingers as early as age 18 months [Tüysüz et al 2018]. Growth. Weight and length at birth are within normal limits. Gradual slowing of growth rate begins in early childhood. Worsening hip and knee contractures add to the poor growth rate. While frank dwarfism does not occur, the height of individuals with ML IIIγ is often below the tenth centile on standard growth curves. Craniofacial. Dysmorphic facial features are absent or minimal in younger children. Although most individuals with ML IIIγ develop coarsening of the facial features, it often occurs in the first two decades of life, which is more gradual than in ML IIIα/β. Ophthalmologic. While the corneae are clear by routine clinical inspection, opacities that do not cause ophthalmologic impairment may be appreciated by slit lamp examination in some individuals [Tüysüz et al 2018]. Respiratory. Individuals with ML IIIγ generally do not have pulmonary impairment; however, mild-to-moderate restrictive lung disease may be present in adults due to abnormalities of the spine and ribs that reduce lung capacity [Oussoren et al 2018]. Cardiovascular. Individuals with ML IIIγ are at risk for cardiac involvement. Although gradual thickening and subsequent mitral valve prolapse and insufficiency of the mitral and aortic valves are common from late childhood onward, cardiac function is normal in most affected adults [Oussoren et al 2018, Tüysüz et al 2018]. Gastrointestinal. Hepatomegaly and splenomegaly are absent. Skeletal / soft connective tissue. Stiffness of finger joints, a cardinal feature, is usually the initial manifestation of the disorder. Moderate-to-severe claw-like flexion deformity of the fingers worsens with time. Limited range of motion of the shoulders is common early in the disease course. Genu valgum deformity occurs in all affected individuals early in the disease. Hip involvement usually develops during the end of adolescence in ML IIIγ (earlier in ML IIIα/β). Hip involvement progresses over years, finally resulting in destruction of the proximal femoral epiphyses. Limited hip mobility and lower-limb pain can be significant and may result in waddling gait with age. Carpal tunnel syndrome develops in most affected individuals and may be clinically significant in the second and third decade [Raas-Rothschild et al 2004, Tüysüz et al 2018, Nampoothiri et al 2019]. Spinal deformities develop over time and include scoliosis and hyperlordosis. In one individual atlantoaxial instability required corrective surgery; however, this complication is very uncommon in ML IIIγ [Tüysüz et al 2018, Nampoothiri et al 2019]. Short neck reported in several individuals had no clinical significance [Tüysüz et al 2018]. Chronic pain syndrome significantly impairs the quality of life. It is common and mainly involves the hips, knees, and entire legs and sometimes the hands. Chronic pain syndrome is attributed to skeletal and connective tissue disease. In some affected individuals spinal cord compression due to spinal stenosis (decreased diameter of the spinal canal) and vertebral osteoarthritic changes may also contribute to the chronic pain syndrome. Osteopenia, confirmed by reduced bone mineral densitometry measured by dual x-ray absorptiometry (DEXA), is common. Neuromotor development and intellect. While motor milestones may be delayed, other aspects of development including language and learning skills are as expected for age. Affected children may require school assistance mostly because of physical limitations. While cognitive function is within the normal range in most affected individuals, a few individuals (probably <10%) have cognitive deficiency. It is still to be determined if this manifestation is related to ML IIIγ given the consanguinity in many reported cases and the possibility of additional genetic causes. Other. The skin may become mildly thickened with time. Recently, scleroderma-like changes were reported in individuals with Moroccan ancestry [Zrhidri et al 2017]. ### Genotype-Phenotype Correlations To date no correlation between severity of disease and type of GNPTG pathogenic variant has been reported; however, predicted loss-of-function variants, such as the recurrent variants c.285dupC, c.445delG, and c.499dupC, are associated with a severe phenotype [Tüysüz et al 2018]. See Table 5 for more details. ### Nomenclature UDP-N-acetylglucosamine: lysosomal hydrolase N-acetylglucosamine 1-phosphotransferasedeficiency disorders. This enzyme is the product of two genes: GNPTAB, encoding the alpha and beta subunits, and GNPTG, encoding the gamma subunit [Bao et al 1996]. Pathogenic variants in: * GNPTAB cause GNPTAB-related disorders, which include the severe phenotype of ML II and the attenuated form of ML IIIα/β; * GNPTG cause ML IIIγ [Cathey et al 2008]. The trivial name of this enzyme is UDPGlcNAc 1-P-transferase; thus, the three ML phenotypes can be considered "UDPGlcNAc 1-P-transferase deficiency disorders" [Leroy 2007]. ML IIIγ was previously referred to as variant pseudo-Hurler polydystrophy* or mucolipidosis IIIC [Cathey et al 2008]. "Pseudo-Hurler polydystrophy" was the term used from 1966 by Maroteaux and Lamy when they first delineated ML III. They used this term because of the resemblance of ML III to Hurler disease, or mucopolysaccharidosis I (MPS I) [Kornfeld & Sly 2001]. ### Prevalence The worldwide estimated incidence of ML II, ML IIIα/β, and ML IIIγ varies between 2.5 and 10 cases per 1,000,000 live births [Velho et al 2019]. The exact prevalence of ML IIIγ is unknown; it is considered an ultra-rare disease. Most individuals with ML IIIγ known to the authors originated from the Mediterranean region [Raas-Rothschild et al 2004, Persichetti et al 2009, Tüysüz et al 2018]. However, more recent reports include individuals with ML IIIγ from other geographic regions including China, India, South America (Brazil), North America, and North Africa [Persichetti et al 2009, Gao et al 2011, Nampoothiri et al 2019, Velho et al 2019], suggesting that the disorder is pan ethnic. ## Differential Diagnosis Mucolipidosis II (ML II), ML IIIα/β, and ML IIIγ are all UDPGlcNAc 1-P-transferase deficiency disorders (see Nomenclature). Whereas the clinical phenotypes of ML IIIα/β and ML IIIγ can be difficult to distinguish, the severe phenotype of ML II is easily differentiated. In general, the ML IIIγ phenotype is less severe than ML IIIα/β. See Table 2 for inherited disorders to consider in the differential diagnosis of ML IIIγ. ### Table 2. Genes to Consider in the Differential Diagnosis of Mucolipidosis III Gamma (ML IIIγ) View in own window Gene(s)DisorderMOIClinical Features of Differential Diagnosis Disorder Overlapping w/ML IIIγDistinguishing from ML IIIγ GNPTABML IIIα/β (see GNPTAB-Related Disorders) 1ARClinical features of ML IIIγ are similar to but milder than those of ML IIIα/β.No specific ethnic predilection has been reported in ML III α/β. 2 CCN6 (WISP3)Progressive pseudorheumatoid dysplasiaAR Joint stiffness & osteoarthritis * Spinal involvement (kyphoscoliosis, platyspondyly) * Claw hands * Absence of dysostosis multiplex * Disease course less progressive * Normal level of serum hydrolases COL2A1Osteoarthritis w/mild chondrodysplasia (see Type II Collagen Disorders Overview)AD * Joint stiffness & osteoarthritis * Mild short stature * Absence of dysostosis multiplex * Disease course less progressive * Normal level of serum hydrolases CTSAJuvenile galactosialidosis (OMIM 256540)AR * Joint stiffness * Corneal clouding * Cardiac abnormalities * Facial coarseness * Dysostosis multiplex * Organomegaly * Normal level of serum hydrolases * ↑ urinary oligosaccharides GLB1MPS IV B 3 (see GLB1-Related Disorders)AR * Joint stiffness * Corneal clouding * Cardiac abnormalities * Normal intelligence * Short stature usually more severe (frank dwarfism) * Absence of dysostosis multiplex * Normal level of serum hydrolases GUSBMPS VII B 4 (OMIM 253220)AR * Dysostosis multiplex * Spinal deformities (kyphoscoliosis) * Coarse facies * Corneal opacities * Cardiac involvement * Normal level of serum hydrolases IDSSlowly progressive MPS II 5XL * Joint stiffness * Corneal clouding * Cardiac abnormalities * Facial coarseness * Dysostosis multiplex * Organomegaly * Cognitive impairment * Hearing impairment * Normal level of serum hydrolases IDUASlowly progressive MPS I 6AR * Joint stiffness * Corneal clouding * Cardiac abnormalities * Facial coarseness * Dysostosis multiplex * Organomegaly * Cognitive impairment * Hearing impairment * Normal level of serum hydrolases MAN2B1Alpha-mannosidosisAR * Facial coarseness * Dysostosis multiplex * Organomegaly * Cognitive impairment * Hearing impairment * Normal level of serum hydrolases SLC17A5Free sialic acid storage disordersAR * Facial coarseness * Skeletal abnormalities * Organomegaly * Cognitive impairment * Neurologic abnormalities * Normal level of serum hydrolases SUMF1Multiple sulfatase deficiencyAR * Joint stiffness * Corneal clouding * Cardiac abnormalities * Facial coarseness * Dysostosis multiplex * Organomegaly * Neurologic abnormalities * Cognitive impairment * Normal level of serum hydrolases AD = autosomal dominant; AR = autosomal recessive; ML = mucolipidosis; MOI = mode of inheritance; MPS = mucopolysaccharidosis; XL = X-linked 1\. Also referred to as pseudo-Hurler polydystrophy 2\. Most individuals with ML IIIγ known to the authors originated from the Mediterranean region [Raas-Rothschild et al 2004, Encarnação et al 2009, Persichetti et al 2009]. 3\. Also referred to as Morquio syndrome type B 4\. Also referred to as Sly disease type B 5\. Also referred to as Hunter syndrome 6\. Also referred to as Hurler-Scheie syndrome or Scheie syndrome Other disorders to consider * Rheumatologic disorders are often suspected in individuals with ML IIIγ because of slowly decreasing range of motion in large and small joints and increasing pain in the hips [Brik et al 1993]. * Rheumatoid arthritis (OMIM 180300) presents with clinical and laboratory signs of inflammation. The activities of the several lysosomal enzymes in serum are normal. Dysostosis multiplex is absent. Family history is not compatible with autosomal recessive inheritance. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with mucolipidosis III gamma (ML IIIγ), the evaluations summarized in Table 3 (if not performed as part of the evaluation that led to the diagnosis) are recommended. ### Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with Mucolipidosis IIIγ View in own window System/ConcernEvaluationComment ConstitutionalHeight, weight, head circumferenceTo assess growth rate SkeletalPain assessmentTo assess pain scores & involvement MusculoskeletalOrthopedics / physical medicine & rehabilitation / PT / OT evaluationIncl assessment of: * Lower limb pain (can be significant) * Gross motor & fine motor skills * Hip, knee contractures * Limited range of motion of shoulders * Stiffness of finger joints & Dupuytren-like palmar contractures (starting in late childhood) * Carpal tunnel syndrome * Odontoid dysplasia & risk of atlanto-axial dislocation * Mobility, activities of daily living, & need for adaptive devices * Need for PT (to improve gross motor skills) &/or OT (to improve fine motor skills) Complete skeletal surveyTo better assess skeletal involvement Metabolic bone diseaseDEXA study; biomarkers reflecting bone metabolismPerform baseline DEXA scan: * Children age >5 yrs * Adults at time of diagnosis DevelopmentDevelopmental assessment * Incl motor, adaptive, cognitive, & speech/language evaluation * Evaluation for early intervention / special education CardiacClinical examination, ECG, echocardiogramTo assess for mitral & aortic valve involvement usually beginning in late childhood OphthalmologicVisual acuity, slit lamp examinationFor evidence of corneal opacities RespiratoryPulmonary consultationLung function studies to evaluate for restrictive lung disease from spine & rib abnormalities Miscellaneous/ OtherConsultation w/clinical geneticist &/or genetic counselorIncl genetic counseling Family support/resourcesAssess: * Use of community or online resources (e.g., Parent to Parent) * Need for social work involvement for parental support OT = occupational therapy; PT = physical therapy ### Treatment of Manifestations Supportive and symptomatic management is indicated. #### Musculoskeletal No measures are known to be effective in treating the progressive limitation of motion in large and small joints. Physiotherapy intervention programs need to be adapted to the affected individual's needs. Short sessions of aqua therapy that are "low impact" in regard to joint and tendon strain are usually well tolerated. Later in the disease course, bone pain of variable intensity may become frequent. Management of pain in the hips is required. In older adolescents and adults, bilateral hip replacement has been successful. In patients with progressive knee involvement, knee replacement has been successful. Casts (especially of the hands) during the night hours are usually well tolerated and appear to improve daily functions. Carpal tunnel signs, and rarely tarsal tunnel symptoms, may require surgical tendon release procedures for temporary relief [Oussoren et al 2018, Tüysüz et al 2018]. In cases with severe spinal deformities with or without spinal cord compression, spinal surgical procedures should be considered. Routine pain assessment and consultation with a pain specialist should be performed as required. Of note, in patients with significant skeletal disease and considerable decrease in bone mineral densitometry (Z score<-2.5), bisphosphonates (oral or intravenous) should be highly considered [Tüysüz et al 2018; Tüysüz, personal communication]. #### Cardiac When significant valvular dysfunction disrupts ventricular function, valve replacement should be seriously considered. However, such complications are rare in ML IIIγ. Antibiotic prophylaxis before minor and major surgical procedures (including dental procedures) is appropriate to prevent bacterial endocarditis. Psychosocial support of patients and families is recommended. #### Anesthesia As with all storage diseases, anesthesia for individuals with ML IIIγ must be well planned. Because of concerns about airway management, surgical intervention should be undertaken only in tertiary care settings with pediatric anesthesiologists and intensive care physicians. The anesthetic team should be aware of the following issues: * Persons with ML IIIγ are small and have a small airway, reduced tracheal suppleness from stiff connective tissue, and progressive narrowing of the airway from mucosal thickening. The use of a smaller endotracheal tube than for age- and size-matched controls is necessary. * Fiberoptic intubation must be available. * Persons with ML IIIγ have short necks, and atlanto-axial instability has been reported [Tüysüz et al 2018]. * Jaw and neck movement can be limited. * Abnormalities of the spine and ribs can limit the individual's capacity to breathe and fully expand the lungs. ### Surveillance ### Table 4. Recommended Surveillance for Individuals with Mucolipidosis IIIγ View in own window System/ConcernEvaluationFrequency ConstitutionalHeight, weight, head circumferenceYearly PainAssessment of pain level by pain specialistYearly MusculoskeletalAssessment of range of motion, stiffness & contractures, carpal tunnel syndrome, tarsal tunnel syndrome, activities of daily livingYearly MobilityBy physical therapist, physiatristYearly Fine motor skillsBy occupational therapistYearly Metabolic bone diseaseDEXA scan * Children: 5-yr intervals after baseline study * Adults w/normal studies: 3-yr intervals * Adolescents & adults w/↓ densitometry: 2-yr intervals RespiratoryLung function studies5-yr intervals CardiacCardiac evaluation incl echocardiographyYearly OphthalmologicMonitor visual acuity & corneal opacities.Yearly Development/ School issuesGeneral evaluationYearly Educational resourcesGeneral evaluationYearly Psychological issuesGeneral evaluationYearly Community resourcesGeneral evaluationYearly ### Agents/Circumstances to Avoid Vigorous stretching exercises are not recommended because they are ineffective, painful, and may damage the surrounding joint capsule and adjacent tendons. ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Mucolipidosis III Gamma	c1854896	29,185	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK24701/	2021-01-18T21:11:17	{"mesh": ["C565367"], "synonyms": []}
Choanal atresia Bilateral membranous choanal atresia in CT scan SpecialtyMedical genetics Frequency1 in 8000 live birth Choanal atresia is a congenital disorder where the back of the nasal passage (choana) is blocked, usually by abnormal bony or soft tissue (membranous) due to failed recanalization of the nasal fossae during fetal development. It was first described by Roederer in 1755.[1] ## Contents * 1 Presentation * 1.1 Associated conditions * 2 Risk factors * 3 Diagnosis * 4 Treatment * 5 In popular culture * 6 References * 7 External links ## Presentation[edit] It can be unilateral or bilateral. * Sometimes, a unilateral choanal atresia is not detected until much later in life because the baby manages to get along with only one nostril available for breathing. * Bilateral choanal atresia is a very serious life-threatening condition because the baby will then be unable to breathe directly after birth as babies are obligate nasal breathers (they mainly use their noses to breathe). In some cases, this may present as cyanosis while the baby is feeding, because the oral air passages are blocked by the tongue, further restricting the airway. The cyanosis may improve when the baby cries, as the oral airway is used at this time. These babies may require airway resuscitation soon after birth. ### Associated conditions[edit] Sometimes babies born with choanal atresia also have other abnormalities:[citation needed] * coloboma * heart defects * intellectual disability * growth impairment * others (see also CHARGE syndrome) Also any condition that causes significant depression of the nasal bridge or midface retraction can be associated with choanal atresia. Examples include the craniosynostosis syndromes such as Crouzon syndrome, Pfeiffer syndrome, Treacher Collins and Antley-Bixler syndrome. ## Risk factors[edit] Very few risk factors for choanal atresia have been identified. While causes are unknown, both genetic and environmental triggers are suspected.[2] One study suggests that chemicals that act as endocrine disrupters may put an unborn infant at risk. A 2012 epidemiological study looked at atrazine, a commonly used herbicide in the U.S., and found that women who lived in counties in Texas with the highest levels of this chemical being used to treat agricultural crops were 80 times more likely to give birth to infants with choanal atresia or stenosis compared to women who lived in the counties with the lowest levels.[3] Another epidemiological report in 2010 found even higher associations between increased incidents of choanal atresia and exposure to second-hand-smoke, coffee consumption, high maternal zinc and B-12 intake and exposure to anti-infective urinary tract medications.[4] The anti-thyroid medication methimazole has been associated with the development of choanal atresia in rare cases if given during the first trimester of pregnancy.[citation needed] ## Diagnosis[edit] Choanal atresia can be suspected if it is impossible to insert a nasal catheter.[5] Also, if one notices a continuous stream of mucus draining from one or both nostrils, it could be a sign of an atresia. Another common sign is cyanosis in an infant while breast feeding, as breathing is dependent on nasal patency in this situation.[5] Diagnosis is confirmed by radiological imaging, usually CT scan.[5] In 1950, in Franklin County, NY, a nurse noticed that a day-old infant turned blue when bottle-fed. “There is something wrong with the baby. We are sending her to Montreal!” The baby was hospitalized over a year. The ENT Surgeon had to gerry-rig a dental drill to accomplish the repair. In 2020, neonatal care for bilateral choanal atresia is much improved.[citation needed] ## Treatment[edit] The only definitive treatment is surgery to correct the defect by perforating the atresia to create a nasopharyngeal airway. If the blockage is caused by bone, this is drilled through and stent inserted. The patient has to have this sucked out by an air vacuum machine. And in later life as a teenager or in early twenties the hole will have to be re-drilled larger. A stent may be inserted[6] to keep the newly formed airway patent or repeated dilatation may be performed.[7] ## In popular culture[edit] In the movie City of Angels, Dr. Maggie Rice (played by Meg Ryan) correctly diagnoses the cause of a newborn baby's failure to thrive as due to choanal atresia. ## References[edit] 1. ^ Kumar, Sunil; Gupta, Sachin; Naglot, Shakuntala; Sahni, J. K. (2013). "Bilateral Choanal Atresia: Is it Really a Surgical Emergency?". Indian Journal of Otolaryngology and Head & Neck Surgery. 65 (Suppl 2): 205–209. doi:10.1007/s12070-011-0304-9. PMC 3738770. PMID 24427647. 2. ^ Choanol atresia, NIH PubMed Health, August 2011. 3. ^ "Study: Exposure to herbicide may increase risk of rare disorder". 4. ^ Epidemiology of choanal atresia - the National Birth Defects Prevention Study, Vijaya Kancherla, University of Iowa, 2010. 5. ^ a b c Choanal atresia - PubMed Health 6. ^ Sadek SA (January 1998). "Congenital bilateral choanal atresia". Int. J. Pediatr. Otorhinolaryngol. 42 (3): 247–56. doi:10.1016/S0165-5876(97)00142-0. PMID 9466228. 7. ^ Gosepath J, Santamaria VE, Lippert BM, Mann WJ (2007). "Forty-one cases of congenital choanal atresia over 26 years--retrospective analysis of outcome and technique". Rhinology. 45 (2): 158–63. PMID 17708465. ## External links[edit] Classification D * ICD-10: Q30.0 * ICD-9-CM: 748.0 * OMIM: 608911 * MeSH: D002754 * DiseasesDB: 31330 * SNOMED CT: 204508009 External resources * MedlinePlus: 001642 * eMedicine: ent/330 * Orphanet: 137914 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Choanal atresia	c0008297	29,186	wikipedia	https://en.wikipedia.org/wiki/Choanal_atresia	2021-01-18T18:44:57	{"mesh": ["D002754"], "umls": ["C0008297", "C0220723"], "orphanet": ["137914"], "wikidata": ["Q662185"]}
Clark and Baraitser (1987) described 2 mentally retarded brothers who also had macrocephaly, 'square' forehead, prominent supraorbital ridges, broad nasal tip, prominent lower lip, large ears, obesity, and macroorchidism. Baraitser et al. (1995) described a family in which 2 male first cousins related through their mothers had features similar to those in the family reported by Clark and Baraitser (1987). The boys had nonspecific mental retardation with macrocephaly and obesity. The authors compared the disorder in both these families to the Atkin-Flaitz syndrome (300431) described by Atkin et al. (1985). The main difference at the clinical level lay in the short stature and hypertelorism of the Atkin-Flaitz patients. The obesity in both conditions suggested Prader-Willi syndrome (176270); however, there was never congenital hypotonia, early feeding difficulties, or nocturnal searching for food. Monteiro de Pina-Neto and Andreotti de Molfetta (1998) reported a 14-year-old Brazilian boy, born to nonconsanguineous parents, who had mental retardation, macrocephaly, tall stature and large hands, obesity, square forehead, prominent supraorbital ridges, prominent lower lip, large ears, a gap between the central incisors, and normal eye spacing. CT scan of the brain showed macrocrania with no abnormalities of the brain. Bone age was compatible with chronologic age, and there were no inborn errors of metabolism. He had a normal karyotype by GTG banding. Macroorchidism that had been noted at age 10 disappeared after puberty. Tabolacci et al. (2005) reported 2 brothers, born of nonconsanguineous parents, who had moderate to severe mental retardation, severe macrocephaly, obesity, characteristic face, big hands and feet, advanced bone age, and brain abnormalities, including frontal cortical atrophy. The height of both brothers, aged 24 and 15 years, respectively, was at the 10th centile, below the midparental target. They both exhibited autistic-like behavior in which they would stand still for several minutes with a fixed facial expression in an almost catatonic state; the parents also reported that they had a high pain threshold. FISH screening revealed a cryptic subtelomeric deletion of chromosome region 22q13 (see 606232), not present in either parent; segregation analysis showed the deletion to be of maternal origin, mostly likely to due germinal mosaicism. Tabolacci et al. (2005) suggested that patients diagnosed with Clark-Baraitser syndrome be tested for submicroscopic 22qter deletion. Mendicino et al. (2005) described a 16-year-old boy, born of nonconsanguineous parents, who had moderate mental retardation associated with tall stature, obesity, macrocephaly, and typical facial features. The patient had behavior problems when thwarted, which the authors noted had been reported in 3 previous patients with Clark-Baraitser syndrome (see Baraitser et al., 1995 and Monteiro de Pina-Neto and Andreotti de Molfetta, 1998). The patient's mother and sister, who were of normal intelligence and had normally spaced eyes, both had a gap between their central upper incisors and a large forehead; the sister also had prominent supraorbital ridges, a broad nasal tip, thick lower lip, and microdontia of upper lateral incisors, and the mother was moderately obese. Subtelomeric chromosome analysis in the patient excluded cryptic rearrangements. Mendicino et al. (2005) suggested that the mild features in the female relatives of this patient might disclose a possible carrier condition and, in combination with the normal cytogenetic investigations, lend support to X-linked inheritance of this syndrome. INHERITANCE \- X-linked GROWTH Height \- Tall stature Weight \- Obesity HEAD & NECK Head \- Macrocephaly Face \- Coarse facial features \- Prominent forehead \- Heavy supraorbital ridges Eyes \- Downslanting palpebral fissures Nose \- Broad nasal tip \- Anteverted nostrils Mouth \- Thick lips \- Prominent lower lip \- Prominent median palatal raphe \- Exaggerated median tongue furrow Teeth \- Central incisor gap \- Microdontia (maxillary lateral incisors) GENITOURINARY Internal Genitalia (Male) \- Macroorchidism SKELETAL \- Joint laxity Spine \- Scoliosis \- Hyperkyphosis Limbs \- Genu valga \- Genu recurvata Hands \- Tapered fingers \- Short, broad hands NEUROLOGIC Central Nervous System \- Mental retardation, moderate to severe \- Seizures ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	CLARK-BARAITSER SYNDROME	c2931130	29,187	omim	https://www.omim.org/entry/300602	2019-09-22T16:20:02	{"mesh": ["C536208"], "omim": ["300602"], "synonyms": ["Alternative titles", "BARAITSER SYNDROME"]}
Pierce and Teneyck (1974) described a black family in which a transverse nasal line of hyperpigmentation was transmitted as a seeming autosomal dominant with male-to-male passage. In none of the affected persons was there a crease, groove or wrinkle such as that described in entry 161500. The family showed independent inheritance of a midtrunk longitudinal line of hyperpigmentation running from the xiphoid to the symphysis pubis. Nose \- Transverse nasal line of hyperpigmentation Inheritance \- Autosomal dominant ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	NASAL HYPERPIGMENTATION, FAMILIAL TRANSVERSE	c1834369	29,188	omim	https://www.omim.org/entry/161530	2019-09-22T16:37:38	{"omim": ["161530"]}
Globozoospermia is a condition that affects only males. It is characterized by abnormal sperm and leads to an inability to father biological children (infertility). Normal sperm cells have an oval-shaped head with a cap-like covering called the acrosome. The acrosome contains enzymes that break down the outer membrane of an egg cell, allowing the sperm to fertilize the egg. The sperm cells of males with globozoospermia, however, have a round head and no acrosome. The abnormal sperm are unable to fertilize an egg cell, leading to infertility. ## Frequency Globozoospermia is a rare condition that is estimated to affect 1 in 65,000 men. It is most common in North Africa, where it accounts for approximately 1 in 100 cases of male infertility. ## Causes Globozoospermia is most commonly caused by mutations in the DPY19L2 gene, which are found in about 70 percent of men with this condition. Mutations in other genes likely also cause globozoospermia. The DPY19L2 gene provides instructions for making a protein that is found in developing sperm cells. The DPY19L2 protein is involved in the development of the acrosome and elongation of the sperm head, which are integral steps in sperm cell maturation. Mutations in the DPY19L2 gene result in a loss of functional DPY19L2 protein. As a result, sperm cells have no acrosome and do not elongate properly. Without an acrosome, the abnormal sperm are unable to get through the outer membrane of an egg cell to fertilize it, leading to infertility in affected men. Researchers have described other characteristics of the abnormal sperm cells that make fertilization of an egg cell difficult, although it is not clear how changes in the DPY19L2 gene are involved in development of these characteristics. ### Learn more about the gene associated with Globozoospermia * DPY19L2 ## 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Globozoospermia	c3151407	29,189	medlineplus	https://medlineplus.gov/genetics/condition/globozoospermia/	2021-01-27T08:25:35	{"gard": ["12502"], "omim": ["613958"], "synonyms": []}
## Description Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996; Risch et al., 1999). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (see ASPG1; 608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008). Genetic studies in autism often include family members with these less stringent diagnoses (Schellenberg et al., 2006). For a discussion of genetic heterogeneity of autism, see 209850. Clinical Features Molloy et al. (2005) reported 34 families in which 1 individual had autism, a relative had either autism or autism spectrum disorder, and both had a definite history of developmental regression. Developmental regression was defined as loss of language skills and/or loss of other socially communicative skills, such as eye contact or gestures, between the ages of 18 and 24 months. However, the authors noted that most children who experience regression do not have completely normal development prior to the regressive episode. Mapping By genomewide linkage analysis in 34 families segregating a phenotype of autism and developmental regression, Molloy et al. (2005) identified a candidate region on chromosome 21p13-q11 (nonparametric lod score of 3.0 near marker D21S1437; maximum multipoint lod score of 3.4 under a dominant mode of inheritance). The strongest evidence for linkage was a 2.7-Mb region between D21S1432 and D21S1899. Significant linkage for this phenotypic subgroup was also identified on chromosome 7q35-q36 (AUTS10; 611016). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	AUTISM, SUSCEPTIBILITY TO, 12	c1970511	29,190	omim	https://www.omim.org/entry/610838	2019-09-22T16:04:05	{"omim": ["610838"]}
A number sign (#) is used with this entry because of evidence that autosomal recessive spastic paraplegia-79 (SPG79) is caused by by homozygous or compound heterozygous mutation in the UCHL1 gene (191342) on chromosome 4p13. Description SPG79 is an autosomal recessive progressive neurologic disorder characterized by onset of spastic paraplegia and optic atrophy in the first decade of life. Additional features are variable, but may include peripheral neuropathy, cerebellar ataxia, and cognitive impairment (summary by Rydning et al., 2017). For a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see SPG5A (270800). Clinical Features Nyberg-Hansen and Refsum (1972) reported 2 brothers, born of unrelated Norwegian parents, with onset of progressive lower and upper limb spasticity in early childhood, followed by onset of progressive visual failure, myopia, and optic atrophy at age 10 years. Features included hyperreflexia, ankle clonus, extensor plantar responses, and intention tremor in the upper limbs. One patient had pes planus and pectus carinatum, and the other had pes cavus. An older sister was similarly affected. Rydning et al. (2017) reported follow-up of this family. The brothers became wheelchair-bound at age 55. At age 62, they had pronounced spasticity with contractures of all joints in the lower limbs, tetraparesis most pronounced in the lower limbs, generalized fasciculations, gaze-evoked horizontal nystagmus, and reduced superficial and dorsal column sensibility. Their sister showed signs of late-onset cerebellar ataxia without spasticity. She also had nystagmus, disrupted saccades, facial myokymia, and reduced sensation. Electrophysiologic studies of the brothers showed an axonal sensorimotor neuropathy. Brain imaging of all patients showed optic atrophy; only 1 of the brothers had mild cerebellar atrophy. Cognitive function was normal in all patients. Bilguvar et al. (2013) reported a consanguineous Turkish family in which 3 of 6 sibs had a neurodegenerative disorder with onset in early childhood. The affected children had normal early development, but developed progressive visual loss around age 5 years. Physical examination in childhood showed optic atrophy, nystagmus, cerebellar ataxia, and spasticity of the lower limbs with hyperreflexia and extensor plantar responses. IQ was mildly decreased (71 and 74) in 2 patients examined. One patient had seizures with 3.5- to 4-Hz spike activity on EEG. As young adults, the patients were blind and had cerebellar ataxia with an inability to stand without assistance, nystagmus, titubation, spasticity, and decreased vibration and position sense due to dorsal column dysfunction. Nerve conduction velocities were normal, but muscles showed myokymic activity. One patient had myotonia. Ophthalmologic examination showed optic atrophy with decreased visual evoked potentials and normal electroretinogram. Brain imaging showed cerebral and cerebellar atrophy. Inheritance The transmission pattern of SPG79 in the family reported by Bilguvar et al. (2013) was consistent with autosomal recessive inheritance. Molecular Genetics In 3 sibs, born of consanguineous Turkish parents, with SPG79, Bilguvar et al. (2013) identified a homozygous missense mutation in the UCHL1 gene (E7A; 191342.0003). The mutation, which was found by homozygosity mapping and whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. In vitro functional expression studies in E. coli showed that the E7A mutant protein had decreased binding to ubiquitin and significantly decreased (less than 10%) hydrolase activity compared to wildtype. The clinical features resembled those of the Uchl1-null mouse (Yamazaki et al., 1988). Bilguvar et al. (2013) noted that neither parent, each of whom was heterozygous for the mutation, had evidence of Parkinson disease. The findings indicated the importance of UCHL1 in the maintenance of nervous system integrity. In 3 sibs, including a pair of monozygotic twin brothers, born of unrelated Norwegian parents, with SPG79, Rydning et al. (2017) identified compound heterozygous missense mutations in the UCHL1 gene: R178Q (191342.0004) and A216D (191342.0005). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. In vitro functional expression studies in E. coli showed that the R178Q mutation resulted in a 4-fold increase in enzyme activity compared to controls. Expression of the A216D mutation resulted in inclusion bodies, containing presumably misfolded, aggregated proteins, so activity assays of this mutant were not possible. Patient fibroblasts showed decreased levels of the UCHL1 protein, at about 25 to 35% of controls, and consisted only of the R178Q mutant; the A216D mutant protein was not detected in patient cells, suggesting that it is degraded. Rydning et al. (2017) noted that the patients did not have cognitive dysfunction, and speculated that the nonsoluble A216D protein results in reduction of UCHL1 function and contributes to neurodegeneration, whereas the increased enzymatic activity of R178Q many compensate and even protect cognitive function. Animal Model The gracile axonal dystrophy (gad) mouse is an autosomal recessive mutant that shows sensory ataxia at an early age, followed by motor ataxia later (Yamazaki et al., 1988). Pathologically, the mutant is characterized by 'dying-back' type axonal degeneration and formation of spheroid bodies in nerve terminals. Pathologic observations in the human have associated brain aging and neurodegenerative diseases with progressive accumulation of ubiquitinated protein conjugates. In gad mice, accumulation of amyloid beta-protein and ubiquitin-positive deposits occur retrogradely along the sensory and motor nervous systems. Suh et al. (1995) showed that the gad mutation is located on mouse chromosome 5. Saigoh et al. (1999) found that the gad mutation is caused by an in-frame deletion including exons 7 and 8 of the Uchl1 gene, encoding the ubiquitin carboxy-terminal hydrolase selectively expressed in the nervous system and testis. The gad allele encodes a truncated Uchl1 protein lacking a segment of 42 amino acids containing a catalytic residue. Since this protein is thought to stimulate protein degradation by generating free monomeric ubiquitin, the gad mutation appears to affect protein turnover. The findings suggested that altered function of the ubiquitin system directly causes neurodegeneration. The gad mouse provides a useful model for investigating human neurodegenerative disorders. INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Head titubation Eyes \- Visual loss, progressive \- Optic atrophy \- Nystagmus \- Myopia \- Absent visual-evoked potentials \- Disrupted saccades \- Normal electroretinogram SKELETAL \- Joint contractures Feet \- Pes cavus \- Pes planus MUSCLE, SOFT TISSUES \- Myokymia \- Fasciculations NEUROLOGIC Central Nervous System \- Spastic paraplegia \- Tetraparesis \- Cerebellar ataxia \- Dysmetria \- Inability to stand without assistance \- Spasticity of the lower limbs \- Hyperreflexia \- Extensor plantar responses \- Ankle clonus \- Intention tremor (in some patients) \- Myotonia (in 1 patient) \- Mild intellectual impairment (1 family) \- Cerebellar atrophy (in some patients) \- Cerebral atrophy (1 family) Peripheral Nervous System \- Impaired distal sensation to vibration and position \- Axonal sensorimotor neuropathy MISCELLANEOUS \- Two unrelated families have been reported (last curated February 2017) \- Onset in first decade \- Progressive disorder MOLECULAR BASIS \- Caused by mutation in the ubiquitin carboxyl-terminal esterase L1 gene (UCHL1, 191342.0003 ) ▲ 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	SPASTIC PARAPLEGIA 79, AUTOSOMAL RECESSIVE	c3809665	29,191	omim	https://www.omim.org/entry/615491	2019-09-22T15:51:55	{"omim": ["615491"], "orphanet": ["352654"], "synonyms": ["Alternative titles", "NEURODEGENERATION WITH OPTIC ATROPHY, CHILDHOOD-ONSET"]}
## Clinical Features Reactive perforating collagenosis, characterized by extrusion of collagen fibers through the epidermis, usually begins in infancy or childhood and appears clinically as recurrent umbilicated papules that resolve spontaneously in 6 to 8 weeks (summary by Trattner et al., 1991). The disorder was first described by Mehregan et al. (1967). Kanan (1974) described 2 unrelated consanguineous families in which 7 adults showed this lesion. Superficial trauma seemed to be a triggering factor in most of the lesions. Cold weather aggravated them. Onset was in early childhood in most. Poliak et al. (1982) described this lesion in black and Hispanic patients with diabetes and renal failure requiring dialysis. The condition must be distinguished from elastosis perforans serpiginosa (130100) and Kyrle disease (149500). Trattner et al. (1991) described brothers with this disorder. In addition to lesions in sun-exposed areas of the face, arms, and legs beginning since the age of 3, one of them had, at age 22, lesions of the lips and oral cavity. Trattner et al. (1991) believed that this was the first report of mucosal involvement in RPC. Inheritance Two sets of sibs were reported by Mehregan (1970). Familial cases were reported also by Nair et al. (1974). Consanguinity in the families with RPC reported by Kanan (1974) suggest autosomal recessive inheritance. Inheritance \- Autosomal recessive Lab \- Collagen fiber extrusion through the epidermis Skin \- Recurrent umbilicated papules, sun-exposed skin, lips and mouth ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	COLLAGENOSIS, FAMILIAL REACTIVE PERFORATING	c1857624	29,192	omim	https://www.omim.org/entry/216700	2019-09-22T16:29:30	{"mesh": ["C565687"], "omim": ["216700"], "orphanet": ["79147"]}
This article does not cite any sources. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Malnutrition–inflammation complex" – news · newspapers · books · scholar · JSTOR (August 2008) (Learn how and when to remove this template message) Malnutrition–inflammation complex Differential diagnosischronic heart failure Malnutrition–inflammation complex (syndrome), abbreviated as "MICS" and also known as "malnutrition–inflammation–cachexia syndrome", is a common condition in chronic disease states such as chronic kidney disease (where it is also known as uremic malnutrition or protein–energy malnutrition) and chronic heart failure. The MICS is believed to be a cause of survival paradoxes seen in these distinct patient populations, also known as reverse epidemiology populations. ## References[edit] This medical symptom article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Malnutrition–inflammation complex	None	29,193	wikipedia	https://en.wikipedia.org/wiki/Malnutrition%E2%80%93inflammation_complex	2021-01-18T18:49:43	{"wikidata": ["Q6744445"]}
A number sign (#) is used with this entry because retinitis pigmentosa-40 (RP40) is caused by homozygous or compound heterozygous mutation in the PDE6B gene (180072), encoding the beta subunit of rod phosphodiesterase, on chromosome 4p16. Mutations in the PDE6B gene also cause congenital stationary night blindness (CSNBAD2; 163500). For a phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000. Clinical Features McLaughlin et al. (1993) identified 6 patients from 3 families with autosomal recessive retinitis pigmentosa (RP) and mutations in the PDE6B gene. All affected individuals had clinical findings typical of RP. They reported absent night vision from early childhood. Ophthalmoscopy revealed attenuated retinal vessels and typical intraretinal bone spicule pigment around the midperiphery. Among 19 Spanish families with autosomal recessive RP, Bayes et al. (1995) identified 1 carrying a homozygous mutation in PDE6B (RP40). The proband was a 39-year-old man who reported absence of night vision since childhood. Ophthalmoscopy revealed a pale retina, attenuated retinal vessels, and typical intraretinal bone spicule pigment in the midperiphery and around the periphery. There was no detectable rod or cone response on ERG. Hmani-Aifa et al. (2009) studied a consanguineous Tunisian family in which autosomal recessive RP cosegregated with Usher syndrome (USH2C; 605472). The family had been originally reported by Hmani et al. (1999). Molecular Genetics McLaughlin et al. (1993) detected 4 mutations in the PDE6B gene (e.g., 180072.0001) in 3 families with autosomal recessive RP. Bayes et al. (1995) found homozygosity for a 71-bp duplication in exon 1 of the PDE6B gene (180072.0006) in 1 of 19 cases of autosomal recessive RP. In a large consanguineous Tunisian family in which Usher syndrome and RP cosegregated, Hmani-Aifa et al. (2009) found homozygosity for a missense mutation in the PDE6B gene (180072.0007) in individuals with isolated RP. Heterozygous mutation carriers were unaffected. Individuals with Usher syndrome carried a homozygous mutation in the GPR98 gene (602851.0006). One family member who was doubly homozygous for both mutations had a more severe ocular phenotype. Two family members who were doubly heterozygous for both mutations were unaffected at ages 82 and 65 years, respectively. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Retinitis pigmentosa \- Intraretinal bone-spicule pigment \- Attenuated retinal vessels \- Absent night vision \- Abnormal rod and cone electroretinograms MOLECULAR BASIS \- Caused by mutation in the retinal rod photoreceptor cGMP phosphodiesterase, beta subunit gene (PDE6B, 180072.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	RETINITIS PIGMENTOSA 40	c0035334	29,194	omim	https://www.omim.org/entry/613801	2019-09-22T15:57:28	{"doid": ["0110375"], "mesh": ["D012174"], "omim": ["613801"], "orphanet": ["791"], "genereviews": ["NBK1417"]}
Desquamative gingivitis Other namesDG SpecialtyPeriodontology Desquamative gingivitis is an erythematous (red), desquamatous (shedding) and ulcerated appearance of the gums.[1] It is a descriptive term and can be caused by several different disorders.[2] ## Contents * 1 Signs and symptoms * 2 Cause * 3 Diagnosis * 3.1 Differential diagnosis * 4 Treatment * 5 History * 6 References * 7 External links ## Signs and symptoms[edit] Desquamative gingivitis involves lesions of the free and attached gingiva. Unlike plaque-induced inflammation of the gums (normal marginal gingivitis), desquamative gingivitis extends beyond the marginal gingiva, involving the full width of the gingiva and sometimes the alveolar mucosa.[3] The term "full width gingivitis" usually refers to the oral lesions of orofacial granulomatosis however.[4] The color is another dissimilarity between typical marginal gingivitis and desquamative gingivitis, in the latter it is dusky red.[3] Plasma cell gingivitis is another form of gingivitis which affects both the attached and free gingiva.[1] ## Cause[edit] Caused by various autoimmune diseases as well as allergies. Erosive lichen planus, mucous membrane pemphigoid, pemphigus vulgaris, erythema exsudativum multiforme and lupus erythematosus. ## Diagnosis[edit] ### Differential diagnosis[edit] Desquamative gingivitis is a descriptive clinical term, not a diagnosis.[1] Dermatologic conditions cause about 75% of cases of desquamative gingivitis, and over 95% of the dermatologic cases are accounted for by either oral lichen planus or cicatricial pemphigoid.[1] The exact cause of desquamative gingivitis cannot be determined about a third of cases.[1] * Oral lichen planus[1] * Cicatricial pemphigoid[1] or less commonly bullous pemphigoid[1] * Pemphigus vulgaris[1] * Linear immunoglobulin A disease[1] * Dermatitis herpetiformis[1] * Lupus erythematosus[1] * Chronic ulcerative stomatitis[1] * Chronic bacterial, fungal, and viral infections[1] * Reactions to medications, mouthwashes, and chewing gum[1] Rare causes include: * Crohn’s disease[1] * Sarcoidosis[1] * Leukemia[1] * factitious (self inflicted) lesions[1] * Squamous cell carcinoma (can be mistaken for desquamative gingivitis)[1] ## Treatment[edit] * Improving oral hygiene * Minimising irritation of the lesions * Specific therapies for the underlying disease (where available) * Local or systemic immunosuppressive or dapsone therapy (notably not corticosteroids) ## History[edit] This condition was first recognized and reported in 1894, but the term desquamative gingivitis was not coined until 1932.[1] ## References[edit] 1. ^ a b c d e f g h i j k l m n o p q r s t u (editors) Newman MG, Takei HH, Klokkevold PR, Carranza FA (2012). Carranza's clinical periodontology (11th ed.). St. Louis, Mo.: Elsevier/Saunders. pp. 111–126. ISBN 978-1-4377-0416-7.CS1 maint: multiple names: authors list (link) CS1 maint: extra text: authors list (link) 2. ^ Lo Russo, L; Fedele, S; Guiglia, R; Ciavarella, D; Lo Muzio, L; Gallo, P; Di Liberto, C; Campisi, G (January 2008). "Diagnostic pathways and clinical significance of desquamative gingivitis". Journal of Periodontology. 79 (1): 4–24. doi:10.1902/jop.2008.070231. PMID 18166088. 3. ^ a b Odell EW (Editor) (2010). Clinical problem solving in dentistry (3rd ed.). Edinburgh: Churchill Livingstone. p. 192. ISBN 9780443067846.CS1 maint: extra text: authors list (link) 4. ^ Welbury R; Duggal M; Hosey MT (2012). Paediatric dentistry (4th ed.). Oxford: Oxford University Press. p. 319. ISBN 978-0199574919. ## External links[edit] Classification D * ICD-10: K05.1 (ILDS K05.130) * ICD-9-CM: 523.10 * v * t * e Oral and maxillofacial pathology Lips * Cheilitis * Actinic * Angular * Plasma cell * Cleft lip * Congenital lip pit * Eclabium * Herpes labialis * Macrocheilia * Microcheilia * Nasolabial cyst * Sun poisoning * Trumpeter's wart Tongue * Ankyloglossia * Black hairy tongue * Caviar tongue * Crenated tongue * Cunnilingus tongue * Fissured tongue * Foliate papillitis * Glossitis * Geographic tongue * Median rhomboid glossitis * Transient lingual papillitis * Glossoptosis * Hypoglossia * Lingual thyroid * Macroglossia * Microglossia * Rhabdomyoma Palate * Bednar's aphthae * Cleft palate * High-arched palate * Palatal cysts of the newborn * Inflammatory papillary hyperplasia * Stomatitis nicotina * Torus palatinus Oral mucosa – Lining of mouth * Amalgam tattoo * Angina bullosa haemorrhagica * Behçet's disease * Bohn's nodules * Burning mouth syndrome * Candidiasis * Condyloma acuminatum * Darier's disease * Epulis fissuratum * Erythema multiforme * Erythroplakia * Fibroma * Giant-cell * Focal epithelial hyperplasia * Fordyce spots * Hairy leukoplakia * Hand, foot and mouth disease * Hereditary benign intraepithelial dyskeratosis * Herpangina * Herpes zoster * Intraoral dental sinus * Leukoedema * Leukoplakia * Lichen planus * Linea alba * Lupus erythematosus * Melanocytic nevus * Melanocytic oral lesion * Molluscum contagiosum * Morsicatio buccarum * Oral cancer * Benign: Squamous cell papilloma * Keratoacanthoma * Malignant: Adenosquamous carcinoma * Basaloid squamous carcinoma * Mucosal melanoma * Spindle cell carcinoma * Squamous cell carcinoma * Verrucous carcinoma * Oral florid papillomatosis * Oral melanosis * Smoker's melanosis * Pemphigoid * Benign mucous membrane * Pemphigus * Plasmoacanthoma * Stomatitis * Aphthous * Denture-related * Herpetic * Smokeless tobacco keratosis * Submucous fibrosis * Ulceration * Riga–Fede disease * Verruca vulgaris * Verruciform xanthoma * White sponge nevus Teeth (pulp, dentin, enamel) * Amelogenesis imperfecta * Ankylosis * Anodontia * Caries * Early childhood caries * Concrescence * Failure of eruption of teeth * Dens evaginatus * Talon cusp * Dentin dysplasia * Dentin hypersensitivity * Dentinogenesis imperfecta * Dilaceration * Discoloration * Ectopic enamel * Enamel hypocalcification * Enamel hypoplasia * Turner's hypoplasia * Enamel pearl * Fluorosis * Fusion * Gemination * Hyperdontia * Hypodontia * Maxillary lateral incisor agenesis * Impaction * Wisdom tooth impaction * Macrodontia * Meth mouth * Microdontia * Odontogenic tumors * Keratocystic odontogenic tumour * Odontoma * Dens in dente * Open contact * Premature eruption * Neonatal teeth * Pulp calcification * Pulp stone * Pulp canal obliteration * Pulp necrosis * Pulp polyp * Pulpitis * Regional odontodysplasia * Resorption * Shovel-shaped incisors * Supernumerary root * Taurodontism * Trauma * Avulsion * Cracked tooth syndrome * Vertical root fracture * Occlusal * Tooth loss * Edentulism * Tooth wear * Abrasion * Abfraction * Acid erosion * Attrition Periodontium (gingiva, periodontal ligament, cementum, alveolus) – Gums and tooth-supporting structures * Cementicle * Cementoblastoma * Gigantiform * Cementoma * Eruption cyst * Epulis * Pyogenic granuloma * Congenital epulis * Gingival enlargement * Gingival cyst of the adult * Gingival cyst of the newborn * Gingivitis * Desquamative * Granulomatous * Plasma cell * Hereditary gingival fibromatosis * Hypercementosis * Hypocementosis * Linear gingival erythema * Necrotizing periodontal diseases * Acute necrotizing ulcerative gingivitis * Pericoronitis * Peri-implantitis * Periodontal abscess * Periodontal trauma * Periodontitis * Aggressive * As a manifestation of systemic disease * Chronic * Perio-endo lesion * Teething Periapical, mandibular and maxillary hard tissues – Bones of jaws * Agnathia * Alveolar osteitis * Buccal exostosis * Cherubism * Idiopathic osteosclerosis * Mandibular fracture * Microgenia * Micrognathia * Intraosseous cysts * Odontogenic: periapical * Dentigerous * Buccal bifurcation * Lateral periodontal * Globulomaxillary * Calcifying odontogenic * Glandular odontogenic * Non-odontogenic: Nasopalatine duct * Median mandibular * Median palatal * Traumatic bone * Osteoma * Osteomyelitis * Osteonecrosis * Bisphosphonate-associated * Neuralgia-inducing cavitational osteonecrosis * Osteoradionecrosis * Osteoporotic bone marrow defect * Paget's disease of bone * Periapical abscess * Phoenix abscess * Periapical periodontitis * Stafne defect * Torus mandibularis Temporomandibular joints, muscles of mastication and malocclusions – Jaw joints, chewing muscles and bite abnormalities * Bruxism * Condylar resorption * Mandibular dislocation * Malocclusion * Crossbite * Open bite * Overbite * Overeruption * Overjet * Prognathia * Retrognathia * Scissor bite * Maxillary hypoplasia * Temporomandibular joint dysfunction Salivary glands * Benign lymphoepithelial lesion * Ectopic salivary gland tissue * Frey's syndrome * HIV salivary gland disease * Necrotizing sialometaplasia * Mucocele * Ranula * Pneumoparotitis * Salivary duct stricture * Salivary gland aplasia * Salivary gland atresia * Salivary gland diverticulum * Salivary gland fistula * Salivary gland hyperplasia * Salivary gland hypoplasia * Salivary gland neoplasms * Benign: Basal cell adenoma * Canalicular adenoma * Ductal papilloma * Monomorphic adenoma * Myoepithelioma * Oncocytoma * Papillary cystadenoma lymphomatosum * Pleomorphic adenoma * Sebaceous adenoma * Malignant: Acinic cell carcinoma * Adenocarcinoma * Adenoid cystic carcinoma * Carcinoma ex pleomorphic adenoma * Lymphoma * Mucoepidermoid carcinoma * Sclerosing polycystic adenosis * Sialadenitis * Parotitis * Chronic sclerosing sialadenitis * Sialectasis * Sialocele * Sialodochitis * Sialosis * Sialolithiasis * Sjögren's syndrome Orofacial soft tissues – Soft tissues around the mouth * Actinomycosis * Angioedema * Basal cell carcinoma * Cutaneous sinus of dental origin * Cystic hygroma * Gnathophyma * Ludwig's angina * Macrostomia * Melkersson–Rosenthal syndrome * Microstomia * Noma * Oral Crohn's disease * Orofacial granulomatosis * Perioral dermatitis * Pyostomatitis vegetans Other * Eagle syndrome * Hemifacial hypertrophy * Facial hemiatrophy * Oral manifestations of systemic disease * v * t * e Dentistry involving supporting structures of teeth (Periodontology) Anatomy * Periodontium * Alveolar bone * Biologic width * Bundle bone * Cementum * Free gingival margin * Gingiva * Gingival fibers * Gingival sulcus * Junctional epithelium * Mucogingival junction * Periodontal ligament * Sulcular epithelium * Stippling Disease Diagnoses * Chronic periodontitis * Localized aggressive periodontitis * Generalized aggressive periodontitis * Periodontitis as a manifestation of systemic disease * Periodontosis * Necrotizing periodontal diseases * Abscesses of the periodontium * Combined periodontic-endodontic lesions Infection * A. actinomycetemcomitans * Capnocytophaga sp. * F. nucleatum * P. gingivalis * P. intermedia * T. forsythia * T. denticola * Red complex * Entamoeba gingivalis (amoebic) * Trichomonas tenax Other * Calculus * Clinical attachment loss * Edentulism * Fremitus * Furcation defect * Gingival enlargement * Gingival pocket * Gingival recession * Gingivitis * Horizontal bony defect * Linear gingival erythema * Occlusal trauma * Periodontal pocket * Periodontal disease * Periodontitis * Plaque * Vertical bony defect Treatment and prevention * Periodontal examination * Ante's law * Brushing * Bleeding on probing * Chlorhexidine gluconate * Flossing * Hydrogen peroxide * Mouthwash * Oral hygiene * Tetracycline * Triclosan * Host modulatory therapy Treatment Conventional therapy * Debridement * Scaling and root planing * Full mouth disinfection * Full mouth ultrasonic debridement Surgery * Apically positioned flap * Bone graft * Coronally positioned flap * Crown lengthening * Free gingival graft * Gingival grafting * Gingivectomy * Guided bone regeneration * Guided tissue regeneration * Enamel matrix derivative * Implant placement * Lateral pedicle graft * Open flap debridement * Pocket reduction surgery * Socket preservation * Sinus lift * Subepithelial connective tissue graft * Tools * Curette * Membrane * Probe * Scaler Important personalities * Tomas Albrektsson * Frank Beube * Per-Ingvar Brånemark * Robert Gottsegen * Gary Greenstein * Jan Lindhe * Brian Mealey * Preston D. Miller * Willoughby D. Miller * Carl E. Misch * John Mankey Riggs * Jay Seibert * Jørgen Slots * Paul Roscoe Stillman * Dennis P. Tarnow * Hom-Lay Wang * James Leon Williams * W. J. Younger Other specialties * Endodontology * Orthodontology * Prosthodontology [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Desquamative gingivitis	c0017577	29,195	wikipedia	https://en.wikipedia.org/wiki/Desquamative_gingivitis	2021-01-18T18:32:59	{"mesh": ["D005882"], "umls": ["C0017577"], "icd-9": ["523.10"], "icd-10": ["K05.1"], "wikidata": ["Q5265026"]}
Intermediate DEND syndrome (iDEND) is a rare mild form of DEND syndrome (see this term), a neonatal diabetes mellitus, developmental delay and epilepsy condition. The intermediate form is characterized clinically by mild motor, speech or cognitive delay and an absence of epilepsy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Intermediate DEND syndrome	None	29,196	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99989	2021-01-23T18:44:32	{"synonyms": ["Developmental delay-epilepsy-neonatal diabetes syndrome, intermediate form"]}
A rare congenital non-syndromic heart malformation characterized by an abnormal protrusion of the interatrial septum into the right or left atrium, or both, during the cardiorespiratory cycle. The defect may be limited to the fossa ovalis or involve the entire septum. It can present as an isolated finding but is more often associated with interatrial shunts, in particular patent foramen ovale. Clinically it increases the risk of peripheral arterial embolism and stroke. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Atrial septal aneurysm	c0521533	29,197	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99107	2021-01-23T17:11:55	{"umls": ["C0521533"], "icd-10": ["Q21.1"]}
Phosphoribosylpyrophosphate synthetase superactivity (PRS superactivity) is characterized by the overproduction and accumulation of uric acid (a waste product of normal chemical processes) in the blood and urine. The overproduction of uric acid can lead to gout, which is arthritis caused by an accumulation of uric acid crystals in the joints. Individuals with PRS superactivity also develop kidney or bladder stones that may result in episodes of acute kidney failure. There are two forms of PRS superactivity, a severe form that begins in infancy or early childhood, and a milder form that typically appears in late adolescence or early adulthood. In both forms, a kidney or bladder stone is often the first symptom. Gout and impairment of kidney function may develop if the condition is not adequately controlled with medication and dietary restrictions. People with the severe form may also have neurological problems, including hearing loss caused by changes in the inner ear (sensorineural hearing loss), weak muscle tone (hypotonia), impaired muscle coordination (ataxia), and developmental delay. ## Frequency PRS superactivity is believed to be a rare disorder. Approximately 30 families with the condition have been reported. More than two thirds of these families are affected by the milder form of the disease. ## Causes Certain mutations in the PRPS1 gene cause PRS superactivity. The PRPS1 gene provides instructions for making an enzyme called phosphoribosyl pyrophosphate synthetase 1, or PRPP synthetase 1. This enzyme helps produce a molecule called phosphoribosyl pyrophosphate (PRPP). PRPP is involved in producing purine and pyrimidine nucleotides. These nucleotides are building blocks of DNA, its chemical cousin RNA, and molecules such as ATP and GTP that serve as energy sources in the cell. PRPP synthetase 1 and PRPP also play a key role in recycling purines from the breakdown of DNA and RNA, a faster and more efficient way of making purines available. In people with the more severe form of PRS superactivity, PRPS1 gene mutations change single protein building blocks (amino acids) in the PRPP synthetase 1 enzyme, resulting in a poorly regulated, overactive enzyme. In the milder form of PRS superactivity, the PRPS1 gene is overactive for reasons that are not well understood. PRPS1 gene overactivity increases the production of normal PRPP synthetase 1 enzyme, which increases the availability of PRPP. In both forms of the disorder, excessive amounts of purines are generated. Under these conditions, uric acid, a waste product of purine breakdown, accumulates in the body. A buildup of uric acid crystals can cause gout, kidney stones, and bladder stones. It is unclear how PRPS1 gene mutations are related to the neurological problems associated with the severe form of PRS superactivity. ### Learn more about the gene associated with Phosphoribosylpyrophosphate synthetase superactivity * PRPS1 ## Inheritance Pattern This condition is inherited in an X-linked pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell sometimes causes the disorder. In most reported cases, affected individuals have inherited the mutation from a parent who carries an altered copy of the PRPS1 gene. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. PRS superactivity may also result from new mutations in the PRPS1 gene and can occur in people with no history of the disorder in their family. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Phosphoribosylpyrophosphate synthetase superactivity	c1970827	29,198	medlineplus	https://medlineplus.gov/genetics/condition/phosphoribosylpyrophosphate-synthetase-superactivity/	2021-01-27T08:25:07	{"mesh": ["C567064"], "omim": ["300661"], "synonyms": []}
A number sign (#) is used with this entry because of evidence that congenital contractures of the limbs and face, hypotonia, and developmental delay (CLIFAHDD) is caused by heterozygous mutation in the NALCN gene (611549) on chromosome 13q33. Description CLIFAHDD is a congenital disorder characterized by congenital contractures of the limbs and face, resulting in characteristic facial features, hypotonia, and variable degrees of developmental delay. All reported cases have occurred de novo (summary by Chong et al., 2015). Clinical Features Chong et al. (2015) reported 14 unrelated children with a similar congenital disorder characterized by severe contractures of the limbs, abnormal facial features, hypotonia, and variable degrees of developmental delay. Characteristic facial features included downslanting palpebral fissures, broad nasal bridge, anteverted nasal tip, large nares, short columella, long philtrum, micrognathia, pursed lips, H-shaped chin dimpling, deep nasolabial folds, and full cheeks. Limb deformities included camptodactyly, adducted thumbs, ulnar deviation, positional foot deformities ranging from varus deformity to severe clubfoot, and contractures of the elbows and knees. Patients also had short neck, scoliosis, and hip contractures. Many patients had neonatal respiratory distress and abnormal breathing patterns. All patients had global developmental delay with poor speech, and some had seizure-like activity. Brain MRI in some patients was normal, whereas others had cerebellar and/or cerebral atrophy. More variable features included gastroesophageal reflux and inguinal or umbilical hernia. Molecular Genetics In 14 unrelated patients with CLIFAHDD, Chong et al. (2015) identified 14 different de novo heterozygous missense mutations in the NALCN gene (see, e.g., 611549.0004-611549.0008). The first 6 mutations were found by exome sequencing, and subsequent mutations were found by sequencing the NALCN gene in 202 samples from patients with a similar disorder. All of the mutations were located in or near the predicted S5 and S6 segments of the protein, which are part of the pore-forming domain. In vitro functional cellular expression studies in HEK293T cells were performed for 2 of the mutations, both of which eliminated expression of the wildtype protein. Chong et al. (2015) postulated a dominant-negative effect. INHERITANCE \- Autosomal dominant HEAD & NECK Face \- Micrognathia \- Long philtrum \- H-shaped chin dimple \- Deep nasolabial folds \- Full cheeks Nose \- Broad nasal bridge \- Anteverted nasal tip \- Large nares \- Short columella Mouth \- Pursed lips Neck \- Short neck RESPIRATORY \- Respiratory insufficiency (newborn period) \- Abnormal respiratory pattern (newborn period) ABDOMEN External Features \- Umbilical hernia Gastrointestinal \- Gastroesophageal reflux disease (in some patients) SKELETAL \- Congenital contractures Spine \- Scoliosis (in some patients) Pelvis \- Hip contractures Limbs \- Elbow contractures \- Knee contractures Hands \- Camptodactyly \- Ulnar deviation \- Adducted thumbs Feet \- Positional foot deformities MUSCLE, SOFT TISSUES \- Hypotonia \- Inguinal hernia NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Speech delay \- Seizure-like activity (in some patients) \- Cerebellar atrophy (in some patients) \- Cerebral atrophy (in some patients) MISCELLANEOUS \- Onset at birth \- All reported mutations have occurred de novo MOLECULAR BASIS \- Caused by mutation in the nonselective sodium leak channel gene (NALCN, 611549.0004 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	CONGENITAL CONTRACTURES OF THE LIMBS AND FACE, HYPOTONIA, AND DEVELOPMENTAL DELAY	c1834523	29,199	omim	https://www.omim.org/entry/616266	2019-09-22T15:49:27	{"mesh": ["C538400"], "omim": ["616266"], "orphanet": ["1147", "2053", "1146"]}

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