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Primary localized cutaneous amyloidosis (PLCA) is a condition in which clumps of abnormal proteins called amyloids build up in the skin, specifically in the wave-like projections (dermal papillae) between the top two layers of skin (the dermis and the epidermis). The primary feature of PLCA is patches of skin with abnormal texture or color. The appearance of these patches defines three forms of the condition: lichen amyloidosis, macular amyloidosis, and nodular amyloidosis. Lichen amyloidosis is characterized by severely itchy patches of thickened skin with multiple small bumps. The patches are scaly and reddish brown in color. These patches usually occur on the shins but can also occur on the forearms, other parts of the legs, and elsewhere on the body. In macular amyloidosis, the patches are flat and dark brown. The coloring can have a lacy (reticulated) or rippled appearance, although it is often uniform. Macular amyloidosis patches are most commonly found on the upper back, but they can also occur on other parts of the torso or on the limbs. These patches are mildly itchy. Nodular amyloidosis is characterized by firm, raised bumps (nodules) that are pink, red, or brown. These nodules often occur on the face, torso, limbs, or genitals and are typically not itchy. In some affected individuals, the patches have characteristics of both lichen and macular amyloidosis. These cases are called biphasic amyloidosis. In all forms of PLCA, the abnormal patches of skin usually arise in mid-adulthood. They can remain for months to years and may recur after disappearing, either at the same location or elsewhere. Very rarely, nodular amyloidosis progresses to a life-threatening condition called systemic amyloidosis, in which amyloid deposits accumulate in tissues and organs throughout the body. ## Frequency PLCA occurs worldwide, most commonly in Southeast Asia and South America. The prevalence of the condition is unknown. ## Causes PLCA can be caused by mutations in the OSMR or IL31RA gene. When caused by an OSMR gene mutation, the condition is classified as type 1, while an IL31RA gene mutation causes type 2. Mutations in either gene are likely involved in lichen and macular amyloidosis, which are thought to be related conditions that arise through similar disease mechanisms. The genetic basis of nodular amyloidosis is unknown. The OSMR and IL31RA genes provide instructions for making parts (subunits) of the interleukin-31 (IL-31) receptor. The subunit produced from OSMR can also pair with a different protein to form the OSM receptor type II. Both receptors are embedded in the membrane of cells throughout the body. Each attaches to a particular protein, fitting together like a lock and its key. This attachment triggers a series of chemical signals inside the cell that directs certain cell functions. OSM receptor type II interacts with a protein called oncostatin M (OSM). Signaling triggered by OSM appears to play a role in many body processes, including the development of blood cells, the maturation of cells to become certain cell types, an immune system response called inflammation, and the self-destruction (apoptosis) of cells. The IL-31 receptor interacts with IL-31, triggering signaling that promotes inflammation and itch (pruritus). OSMR gene mutations reduce signaling stimulated by OSM and IL-31, while IL31RA gene mutations impair only IL-31 signaling. How PLCA develops is not completely understood. In lichen and macular amyloidosis, it is thought that scratching the itchy skin causes skin cells to undergo apoptosis, releasing proteins that abnormally clump together and form amyloids. The proteins that make up the amyloids are abnormal versions of proteins called keratins. The role of gene mutations in this process is still being determined. Because signaling triggered by IL-31 normally stimulates itching, it is unclear how a reduction of this signaling is involved in itchy skin. Also unclear is how reduced IL-31 signaling is related to apoptosis or amyloid formation. Researchers speculate that a reduction of signaling triggered by OSM may make cells more likely to undergo apoptosis, which may promote amyloid buildup. In nodular amyloidosis, the amyloids are composed of abnormal versions of proteins called immunoglobulin light chains released from certain blood cells called plasma cells. However, it is unknown how this form of PLCA develops. Many people with PLCA do not have a mutation in the OSMR or IL31RA gene. The cause of the condition in these cases is unknown. ### Learn more about the genes associated with Primary localized cutaneous amyloidosis * IL31RA * OSMR ## Inheritance Pattern In most cases, PLCA is not inherited and occurs in people with no history of the condition in their family. When the condition runs in families, it is usually inherited in an autosomal dominant pattern, which means one copy of the altered OSMR or IL31RA gene in each cell is sufficient to cause the disorder. In these cases, the affected person has one parent with the condition. Rarely, when caused by a mutation in the OSMR gene, PLCA 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	Primary localized cutaneous amyloidosis	c4551501	29,800	medlineplus	https://medlineplus.gov/genetics/condition/primary-localized-cutaneous-amyloidosis/	2021-01-27T08:24:42	{"gard": ["132"], "omim": ["105250", "613955"], "synonyms": []}
Human disease Hyperestrogenism Other namesHyperestrogenic state, SpecialtyEndocrinology Hyperestrogenism, hyperestrogenic state, or estrogen excess, is a medical condition characterized by an excessive amount of estrogenic activity in the body.[1] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 4 Treatments * 5 See also * 6 References ## Signs and symptoms[edit] Signs of hyperestrogenism may include heightened levels of one or more of the estrogen sex hormones (usually estradiol and/or estrone), lowered levels of follicle-stimulating hormone and/or luteinizing hormone (due to suppression of the hypothalamic–pituitary–gonadal axis by estrogen), and lowered levels of androgens such as testosterone (generally only relevant to males).[1] Symptoms of the condition in women may consist of menstrual irregularities, amenorrhea, abnormal vaginal bleeding, and enlargement of the uterus and breasts.[1][2] It may also present as isosexual precocity in children[1][2] and as hypogonadism, gynecomastia, feminization, impotence, and loss of libido in males.[3] If left untreated, hyperestrogenism may increase the risk of estrogen-sensitive cancers such as breast cancer later in life.[citation needed] ## Causes[edit] Hyperestrogenism can be caused by ovarian tumors,[2] genetic conditions such as aromatase excess syndrome (also known as familial hyperestrogenism), or overconsumption of exogenous sources of estrogen, including medications used in hormone replacement therapy and hormonal contraception.[3] Liver cirrhosis is another cause, though through lowered metabolism of estrogen, not oversecretion or overconsumption like the aforementioned. It's necessary to know there exist two kinds of hyperestrogenism: Absolute (more concentration than usual of estrogen) and relative (we can have a normal concentration of estrogen, but it's higher with respect to progesterone). An example of absolute hyperestrogenism could be: persistent follicles that later undergo atresia without ovulating; and the example of relative hyperestrogenism: luteal insufficiency.[citation needed] ## Diagnosis[edit] This section is empty. You can help by adding to it. (February 2017) ## Treatments[edit] Treatment may consist of surgery in the case of tumors,[1] lower doses of estrogen in the case of exogenously-mediated estrogen excess, and estrogen-suppressing medications like gonadotropin-releasing hormone analogues and progestogens. In addition, androgens may be supplemented in the case of males.[citation needed] ## See also[edit] * Aromatase deficiency * Aromatase excess syndrome * Estrogen insensitivity syndrome * High-dose estrogen * Hyperandrogenism * Hypergonadism * Hypergonadotropic hypergonadism * Hypoandrogenism * Hypoestrogenism * Hypogonadism ## References[edit] 1. ^ a b c d e Norman Lavin (1 April 2009). Manual of Endocrinology and Metabolism. Lippincott Williams & Wilkins. p. 274. ISBN 978-0-7817-6886-3. Retrieved 5 June 2012. 2. ^ a b c Ricardo V. Lloyd (14 January 2010). Endocrine Pathology:: Differential Diagnosis and Molecular Advances. Springer. p. 316. ISBN 978-1-4419-1068-4. Retrieved 5 June 2012. 3. ^ a b Lewis R. Goldfrank; Neal Flomenbaum (24 March 2006). Goldfrank's Toxicologic Emergencies. McGraw-Hill Professional. p. 443. ISBN 978-0-07-147914-1. Retrieved 5 June 2012. * v * t * e Gonadal disorder Ovarian * Polycystic ovary syndrome * Premature ovarian failure * Estrogen insensitivity syndrome * Hyperthecosis Testicular Enzymatic * 5α-reductase deficiency * 17β-hydroxysteroid dehydrogenase deficiency * aromatase excess syndrome Androgen receptor * Androgen insensitivity syndrome * Familial male-limited precocious puberty * Partial androgen insensitivity syndrome Other * Sertoli cell-only syndrome General * Hypogonadism * Delayed puberty * Hypergonadism * Precocious puberty * Hypoandrogenism * Hypoestrogenism * Hyperandrogenism * Hyperestrogenism * Postorgasmic illness syndrome * Cytochrome P450 oxidoreductase deficiency * Cytochrome b5 deficiency * Androgen-dependent condition * Aromatase deficiency * Complete androgen insensitivity syndrome * Mild androgen insensitivity syndrome * Hypergonadotropic hypogonadism * Hypogonadotropic hypogonadism * Fertile eunuch syndrome * Estrogen-dependent condition * Premature thelarche * Gonadotropin insensitivity * Hypergonadotropic hypergonadism [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Hyperestrogenism	c0154209	29,801	wikipedia	https://en.wikipedia.org/wiki/Hyperestrogenism	2021-01-18T18:57:31	{"umls": ["C0154209"], "wikidata": ["Q5957980"]}
A number sign (#) is used with this entry because of evidence that reticulate acropigmentation of Kitamura (RAK) is caused by heterozygous mutation in the ADAM10 gene (602192) on chromosome 15q21. Description Reticulate acropigmentation of Kitamura (RAK) is a rare pigmentary disorder that usually shows an autosomal dominant pattern of inheritance with high penetrance. Typical features include reticulate, slightly depressed, sharply demarcated brown macules without hypopigmentation, affecting the dorsa of the hands and feet in the first or second decade of life. The macules gradually darken and extend to the proximal regions of the extremities; progression of the eruptions stops in middle age. The increased pigmentation is found on the flexor aspects of the wrists, neck, patella, and olecranon. Other features include breaks in the epidermal ridges on the palms and fingers, palmoplantar pits, partial alopecia, and occasionally plantar keratoderma. Histopathologically, the brown macules show pigmentation in the tip of rete ridges with thinning of the epidermis, elongation and thinning of the rete ridges, and slight hyperkeratosis without parakeratosis. Only a few inflammatory cell infiltrates and no incontinentia pigmenti are seen in the dermis (summary by Kono et al., 2013). ### Review of Reticulate Pigment Disorders Muller et al. (2012) reviewed the spectrum of reticulate pigment disorders of the skin, tabulating all reported cases of patients with Dowling-Degos disease (see DDD1; 179850), reticulate acropigmentation of Kitamura (RAK), reticulate acropigmentation of Dohi (DSH, RAD; 127400), Galli-Galli disease (GGD), and Haber syndrome (HS). Of 82 cases, 26 (31.7%) were clinically diagnosed as DDD, 13 (15.9%) as RAD, 11 (13.4%) as GGD, 8 (9.8%) as RAK, and 8 (9.8%) as HS; in addition, 16 (19.5%) of the cases showed overlap between DDD and RAK. Muller et al. (2012) also published photographs of an affected individual exhibiting an overlap of clinical features of DDD, GGD, RAD, and RAK. The authors noted that in reticulate disorders of the skin, the main disease entity is DDD, with a subset of cases exhibiting acantholysis (GGD), facial erythema (HS), or an acral distribution (RAD; RAK). Muller et al. (2012) concluded that all reticulate pigment diseases of the skin are varying manifestations of a single entity. For a discussion of genetic heterogeneity of reticulate pigment disorders, see 179850. Molecular Genetics By whole-exome sequencing in a 4-generation Japanese family with autosomal dominant reticulate acropigmentation, Kono et al. (2013) identified a 5-bp insertion in the ADAM10 gene (602192.0001) that segregated with disease in the family and was not found in 102 Japanese controls. Sanger sequencing of ADAM10 in 5 more patients from 4 unrelated Japanese families identified 4 different mutations, including a splice site (602192.0002), a nonsense (Y143X; 602192.0003), and a missense (C524Y; 602192.0005) mutation as well as a 1-bp deletion (602192.0004). KRT5 (148040) mutations were excluded in all of the patients. INHERITANCE \- Autosomal dominant SKIN, NAILS, & HAIR Skin \- Reticulate hyperpigmented macules which darken over time and appear initially on dorsa of hands and feet but progress to flexor aspects of proximal extremities \- Breaks in epidermal ridges of palms and fingers \- Palmoplantar pits \- Plantar keratoderma (in some patients) Skin Histology \- Pigmentation in tip of rete ridges \- Epidermal thinning \- Elongation and thinning of rete ridges \- Slight hyperkeratosis \- Few inflammatory cell infiltrates Hair \- Partial alopecia MISCELLANEOUS \- Onset in first or second decade of life MOLECULAR BASIS \- Caused by mutation in the gene encoding a disintegrin and metalloproteinase domain-10 (ADAM10, 602192.0001 ) ▲ 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	RETICULATE ACROPIGMENTATION OF KITAMURA	c0406811	29,802	omim	https://www.omim.org/entry/615537	2019-09-22T15:51:51	{"doid": ["0060258"], "mesh": ["C562924"], "omim": ["615537"], "orphanet": ["178307"], "synonyms": ["Alternative titles", "ACROPIGMENTATIO RETICULARIS", "RETICULATE PIGMENTATION OF KITAMURA", "KITAMURA RETICULATE ACROPIGMENTATION"]}
Sensenbrenner syndrome Other namesCranioectodermal dysplasia This condition is inherited in an autosomal recessive manner Sensenbrenner syndrome (OMIM #218330) is a rare (less than 20 cases reported by 2010) multisystem disease first described by Judith A. Sensenbrenner in 1975.[1] It is inherited in an autosomal recessive fashion, and a number of genes appear to be responsible. Three genes responsible have been identified: intraflagellar transport (IFT)122 (WDR10),[2] IFT43—a subunit of the IFT complex A machinery of primary cilia,[3] and WDR35 (IFT121: TULP4)[4] It is also known as Sensenbrenner–Dorst–Owens syndrome, Levin syndrome I and cranioectodermal dysplasia (CED) ## Contents * 1 Presentation * 2 Cause * 3 Pathophysiology * 3.1 Pathology * 4 Diagnosis * 5 Treatment * 6 References * 7 External links ## Presentation[edit] These are pleomorphic and include[citation needed] * dolichocephaly (with or without sagittal suture synostosis) * microcephaly * pre- and postnatal growth retardation * brachydactyly * narrow thorax * rhizomelic dwarfism * epicanthal folds * hypodontia and/or microdontia * sparse, slow-growing, hyperpigmented, fine hair * nail dysplasia * hypohydrosis * chronic kidney failure * heart defects * liver fibrosis * visual deficits * photophobia * hypoplasia of the posterior corpus callosum * aberrant calcium homeostasis Electroretinography shows gross abnormalities. Two fetuses of 19 and 23 weeks gestation have also been reported.[5] They showed acromesomelic shortening, craniofacial characteristics with absence of craniosynostosis, small kidneys with tubular and glomerular microscopic cysts, persistent ductal plate with portal fibrosis in the liver, small adrenals, an enlarged cisterna magna and a posterior fossa cyst. ## Cause[edit] The gene IFT122 is located on the long arm of chromosome 3 (3q21-3q24). The gene lies on the Watson (plus) strand and is 80,047 bases in length. The encoded protein has 1241 amino acids and a predicted weight of 141.825 kiloDaltons (kDa). It is a member of the WD repeat protein family.[citation needed] WDR35 is also a member of the WD repeat protein family. The gene is located on the short arm of chromosome 2 (2p24.1–2p24.3) The gene lies on the Crick (minus) strand and is 79,745 bases in length. The encoded protein is 1181 amino acids in length and its predicted molecular weight is 133.547 kiloDaltons.[citation needed] The gene IFT43 lies on the Watson (plus) strand of the long arm of chromosome 14 (14q24.3). A mouse model for IFT122 has been created.[6] Mutants deficient in IFT122 show multiple developmental defects (many are lethal), including exencephaly, situs viscerum inversus, delay in turning, hemorrhage and defects in limb development. In the node, primary cilia were absent or malformed in homozygous mutant and heterozygous embryos, respectively. Impairment of the Sonic hedgehog pathway was apparent in both neural tube patterning (expansion of motoneurons and rostrocaudal level-dependent contraction or expansion of the dorsolateral interneurons) and limb patterning (ectrosyndactyly). ## Pathophysiology[edit] The IFT machinery is organized in two structural complexes — A and B. These complexs are involved in the coordinated movement of macromolecular cargo from the basal body along axonemal microtubules to the cilium tip and back again. The anterograde movement of IFT particles out to the distal tip of cilia and flagella is driven by kinesin-2 while the retrograde movement of particles back to the cell body is driven by cytoplasmic dynein 1b/2[citation needed] The IFT-A protein complex is involved in retrograde ciliary transport. Disruption of IFT43 disturbs transport from the ciliary tip to the base. Anterograde transport in the opposite direction remains normal resulting in accumulation of the IFT complex B proteins in the ciliary tip.[citation needed] ### Pathology[edit] The visual defects are due to photoreceptor dystrophy. The chronic kidney failure is due to tubulointerstitial nephropathy. The liver fibrosis is secondary to ductal plate malformation. ## Diagnosis[edit] This section is empty. You can help by adding to it. (August 2017) ## Treatment[edit] This section is empty. You can help by adding to it. (August 2017) ## References[edit] 1. ^ Sensenbrenner JA, Dorst JP, Owens RP (1975). "New syndrome of skeletal, dental and hair anomalies". Birth Defects Orig. Artic. Ser. 11 (2): 372–9. PMID 1227553. 2. ^ Walczak-Sztulpa J, Eggenschwiler J, Osborn D, Brown DA, Emma F, Klingenberg C, Hennekam RC, Torre G, Garshasbi M, Tzschach A, Szczepanska M, Krawczynski M, Zachwieja J, Zwolinska D, Beales PL, Ropers HH, Latos-Bielenska A, Kuss AW (2010). "Cranioectodermal Dysplasia, Sensenbrenner syndrome, is a ciliopathy caused by mutations in the IFT122 gene". Am. J. Hum. Genet. 86 (6): 949–56. doi:10.1016/j.ajhg.2010.04.012. PMC 3032067. PMID 20493458. 3. ^ Arts HH, Bongers EM, Mans DA, van Beersum SE, Oud MM, Bolat E, Spruijt L, Cornelissen EA, Schuurs-Hoeijmakers JH, de Leeuw N, Cormier-Daire V, Brunner HG, Knoers NV, Roepman R (2011). "C14ORF179 encoding IFT43 is mutated in Sensenbrenner syndrome". J. Med. Genet. 48 (6): 390–5. doi:10.1136/jmg.2011.088864. PMID 21378380. 4. ^ Gilissen C, Arts HH, Hoischen A, Spruijt L, Mans DA, Arts P, van Lier B, Steehouwer M, van Reeuwijk J, Kant SG, Roepman R, Knoers NV, Veltman JA, Brunner HG (2010). "Exome sequencing identifies WDR35 variants involved in Sensenbrenner syndrome". Am. J. Hum. Genet. 87 (3): 418–23. doi:10.1016/j.ajhg.2010.08.004. PMC 2933349. PMID 20817137. 5. ^ Konstantinidou AE, Fryssira H, Sifakis S, Karadimas C, Kaminopetros P, Agrogiannis G, Velonis S, Nikkels PG, Patsouris E (2009). "Cranioectodermal dysplasia: a probable ciliopathy". Am. J. Med. Genet. A. 149A (10): 2206–11. doi:10.1002/ajmg.a.33013. PMID 19760621. 6. ^ Cortellino S, Wang C, Wang B, Bassi MR, Caretti E, Champeval D, Calmont A, Jarnik M, Burch J, Zaret KS, Larue L, Bellacosa A (2009). "Defective ciliogenesis, embryonic lethality and severe impairment of the Sonic Hedgehog pathway caused by inactivation of the mouse complex A intraflagellar transport gene Ift122/Wdr10, partially overlapping with the DNA repair gene Med1/Mbd4". Dev. Biol. 325 (1): 225–37. doi:10.1016/j.ydbio.2008.10.020. PMC 2645042. PMID 19000668. ## External links[edit] Classification D * ICD-10: Q87.5 * OMIM: 218330 * DiseasesDB: 34682 External resources * GeneReviews: Cranioectodermal Dysplasia * Orphanet: 1515 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Sensenbrenner syndrome	c3150874	29,803	wikipedia	https://en.wikipedia.org/wiki/Sensenbrenner_syndrome	2021-01-18T18:42:27	{"gard": ["359"], "umls": ["C3150874"], "orphanet": ["1515"], "wikidata": ["Q7451019"]}
A number sign (#) is used with this entry because Stargardt disease-4 (STGD4) is caused by heterozygous mutation in the prominin-1 gene (PROM1; 604365). For a general phenotypic description and a discussion of genetic heterogeneity of Stargardt disease, see STGD1 (248200). Description Stargardt disease is the most common hereditary macular dystrophy and is characterized by decreased central vision, atrophy of the macula and underlying retinal pigment epithelium, and frequent presence of prominent flecks in the posterior pole of the retina. STGD is most commonly inherited as an autosomal recessive trait (see 248200), but STGD4 is inherited as an autosomal domiant trait (summary by Kniazeva et al., 1999). Clinical Features Kniazeva et al. (1999) studied 26 members of a 3-generation Caribbean kindred with an autosomal dominant Stargardt-like phenotype. Twelve living individuals in 2 generations were thought to be affected on the basis of decreased visual acuity and macular atrophy. Fluorescein angiography performed in 4 affected subjects demonstrated the characteristic dark-choroid pattern of STGD. Three patients showed typical STGD flavimaculatus flecks. Two affected subjects studied by electroretinography showed normal rod photoreceptor response and mildly decreased cone photoreceptor response in one case and very mildly reduced rod response and mildly reduced cone response in the other case. Mapping Kniazeva et al. (1999) performed a genomewide search in a 3-generation Caribbean family segregating an autosomal dominant Stargardt-like phenotype and demonstrated linkage to chromosome 4p, with a maximum lod score of 5.12 at a recombination fraction of 0.0 for marker D4S403. Analysis of extended haplotypes localized the disease gene to an interval of approximately 12 cM between loci D4S1582 and D4S2397. Molecular Genetics In affected members of a 4-generation Caribbean family with Stargardt disease, previously reported by Kniazeva et al. (1999), Yang et al. (2008) identified heterozygosity for a missense mutation in the PROM1 gene (604365.0003). (The citation for this family was erroneous in the article published by Yang et al., 2008 (Zhang, 2009).) Yang et al. (2008) identified the same mutation in a family with retinal macular dystrophy (MCDR2; 608051) and in a family with cone-rod dystrophy (CORD12; 612657); the mutation was not found in 400 matched controls. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	STARGARDT DISEASE 4	c0271093	29,804	omim	https://www.omim.org/entry/603786	2019-09-22T16:12:37	{"doid": ["0050817"], "mesh": ["C535804"], "omim": ["603786"], "orphanet": ["827"]}
Bohring-Opitz syndrome is a rare genetic condition characterized by intrauterine growth restriction (IUGR), failure to thrive, sleep apnea, developmental delay, hypotonia, flexion of the elbows and wrists, excessive hair growth, Wilm's tumor, microcephaly, brain malformations, and distinctive facial features. The condition is caused by mutations in the ASXL1 gene. The inheritance of Bohring-Opitz syndrome remains unknown, as nearly all cases to date have occurred sporadically. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Bohring-Opitz syndrome	c0796232	29,805	gard	https://rarediseases.info.nih.gov/diseases/10140/bohring-opitz-syndrome	2021-01-18T18:01:45	{"mesh": ["C537419"], "omim": ["605039"], "umls": ["C0796232"], "orphanet": ["97297"], "synonyms": ["Opitz trigonocephaly-like syndrome", "Bohring syndrome", "BOS syndrome", "C-like syndrome"]}
A number sign (#) is used with this entry because of evidence that lethal congenital contracture syndrome-7 (LCCS7) is caused by homozygous mutation in the CNTNAP1 gene (602346) on chromosome 17q21. Biallelic mutation in the CNTNAP1 gene can also cause congenital hypomyelinating neuropathy-3 (CHN3; 618186), a similar disorder with less prominent contractures. LCCS7 and CHN3 represent a phenotypic spectrum resulting from mutations in the CNTNAP1 gene. Description Lethal congenital contracture syndrome-7, an axoglial form of arthrogryposis multiplex congenita (AMC), is characterized by congenital distal joint contractures, polyhydramnios, reduced fetal movements, and severe motor paralysis leading to death early in the neonatal period (Laquerriere et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of lethal congenital contracture syndrome, see LCCS1 (253310). Clinical Features Laquerriere et al. (2014) reported 7 newborns from 4 unrelated consanguineous families (A641, K182, K199, B207) who were diagnosed with distal arthrogryposis multiplex congenita by fetal ultrasound between 28 and 32 weeks of gestation. All 7 had polyhydramnios, distal joint contractures, and severe motor paralysis at birth, leading to death within the first 2 months of life. At least 5 of the patients were known to have fetal hypo- or akinesia. One patient had micrognathia and facial diplegia. None of the patients had pterygium, cleft palate, or hygroma. Laquerriere et al. (2014) noted a dramatic reduction of motor nerve conduction velocities. Transmission electron microscopic analysis of sciatic nerve showed marked widening of the nodes of Ranvier and thin myelin sheaths as compared to control tissue of matched gestational age. Lakhani et al. (2017) reported a large consanguineous Arab family from Qatar in which 3 sisters had LCCS7. The pregnancies were complicated by polyhydramnios, and prenatal ultrasound showed mild contractures or abnormal positioning of the limbs. Two of the patients lacked spontaneous movements and had poor breathing leading to death in the minutes after birth, whereas the third was immediately intubated and survived. She had microphthalmia, facial weakness, and a stiff jaw. At 13 years of age, this patient was still alive, but she was severely hypotonic, in a vegetative state, and intubated, with severe contractures and muscle wasting. Muscle biopsy suggested neurogenic muscular atrophy. Motor nerve conduction velocities were markedly reduced (about 10 m/s) in the upper limbs with no responses in the lower limbs; sensory responses were absent. Brain imaging in this patient showed profound cerebral and cerebellar atrophy with almost no white matter, thin corpus callosum, and small basal ganglia and hippocampi. Family history revealed 6 first cousins who reportedly died early with a muscle disorder, but no further information was available. Inheritance The transmission pattern of LCCS7 in the consanguineous families reported by Laquerriere et al. (2014) was consistent with autosomal recessive inheritance. Molecular Genetics By genetic mapping and whole-exome sequencing, Laquerriere et al. (2014) identified homozygous frameshift mutations in the CNTNAP1 gene (602346.0001-602346.0003) in 7 newborns from 4 unrelated consanguineous families with lethal arthrogryposis multiplex congenita. In 3 sibs, born of consanguineous parents from Qatar, with LCCS7, Lakhani et al. (2017) identified a homozygous frameshift mutation in the CNTNAP1 gene (602346.0011). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed, but the mutation was predicted to result in nonsense-mediated mRNA decay and a complete loss of function. Loss of the CASPR protein, which is encoded by the CNTNAP1 gene, results in improper organization of axoglial junctions in nerves. The loss of these axoglial junctions results in swelling of neuronal axons, decreased nerve conduction, reduced motor function, and death. In addition, the loss of myelination also affects the central nervous system. INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Facial diplegia \- Micrognathia RESPIRATORY \- Respiratory distress secondary to motor nerve paralysis ABDOMEN Gastrointestinal \- Difficulty swallowing SKELETAL \- Arthrogryposis multiplex congenita, distal Limbs \- Multiple distal joint contractures \- Flexion contracture of knees Hands \- Flexion contracture of fingers Feet \- Flexion contracture ankle MUSCLE, SOFT TISSUES \- Hypotonia \- Muscle atrophy \- Neurogenic muscle weakness NEUROLOGIC Central Nervous System \- Absence of development \- Lack of spontaneous movements \- Hypotonia \- Cerebral atrophy \- Cerebellar atrophy \- Lack of white matter volume \- Thin corpus callosum \- Small basal ganglia Peripheral Nervous System \- Areflexia \- Motor paralysis, severe, present at birth \- Reduced motor nerve conduction velocities \- Marked widening of the node of Ranvier seen on biopsy \- Absence of large myelinated axons \- Thin myelin sheath PRENATAL MANIFESTATIONS Movement \- Fetal hypokinesia \- Fetal akinesia Amniotic Fluid \- Polyhydramnios MISCELLANEOUS \- Death in neonatal period \- Onset between 28-32 weeks of gestation MOLECULAR BASIS \- Caused by mutation in the contactin-associated protein-like 1 gene (CNTNAP1, 602346.0001 ) ▲ 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 7	c4225386	29,806	omim	https://www.omim.org/entry/616286	2019-09-22T15:49:25	{"omim": ["616286"], "orphanet": ["2680"], "synonyms": []}
A number sign (#) is used with this entry because of evidence that Rajab interstitial lung disease with brain calcifications (RILCBC) is caused by homozygous or compound heterozygous mutation in the FARSB gene (609690) on chromosome 2q36. Description Rajab interstitial lung disease with brain calcifications (RILCBC) is an autosomal recessive multisystem disorder with a highly variable phenotype. Most patients present in infancy or early childhood with poor growth and interstitial lung disease, which may lead to death. Some may also have liver, skeletal, and renal abnormalities, and most have intracranial calcifications on brain imaging. Some may have early impaired motor development, but most have normal cognitive development (summary by Xu et al., 2018). Clinical Features Rajab et al. (2009) described 2 interrelated Omani families in which 8 children had brain calcifications of basal ganglia and cortex, mild developmental delay, poor school performance, microcephaly, growth delay, and osteopenia. The widespread brain calcifications were similar to those in Aicardi-Goutieres syndrome (225750) and Coats plus syndrome (612199). Rajab et al. (2009) suggested that the disorder in the Omani families represents a new variant or possibly a new disorder of inherited brain calcification. Zadjali et al. (2018) reported follow-up of the family reported by Rajab et al. (2009), noting that 3 patients had died of pulmonary disease, but the remaining patients were able to complete school and live independently. Antonellis et al. (2018) reported a boy, born of unrelated parents, with a complex multisystem neurodevelopmental disorder resulting in death at age 32 months. The pregnancy was complicated by oligohydramnios, and the infant showed intrauterine growth retardation. He presented at age 5 months with failure to thrive, developmental delay, inguinal hernia, tachypnea, and chronic cough. He had sunken eyes, prominent cheeks, high-arched palate, hypotonia, joint hyperlaxity, and small scrotum and phallus. Detailed workup identified multiple systemic problems, including hypocalcemia, vitamin A and D deficiency, liver disease with hypoalbuminemia, anasarca, ascites, abnormal liver enzymes, coagulation defects, episodic DVT, osteopenia with rickets, recurrent infections, hypoglycemia, seizures, and chronic interstitial lung disease with pulmonary hypertension and respiratory insufficiency. He also had gastroesophageal reflux disease, anemia, pancytopenia, and increased renal echogenicity, possibly suggesting renal disease. Liver imaging and biopsy showed hepatic steatosis, cirrhosis, bile duct proliferation, cholestasis, and portal hypertension. Brain imaging showed abnormal periventricular white matter, basal ganglia echogenicity, cerebral volume loss, and incomplete closure of the Sylvian fissures, but myelination was normal. The patient showed abnormal eye movements and dysconjugate gaze. Antonellis et al. (2018) noted the phenotypic overlap with patients with mutations in other aminoacyl-tRNA synthetase genes, including AARS (601065), LARS (151350), and MARS (156560). Xu et al. (2018) reported 5 patients from 4 unrelated families with a similar phenotype comprising early-onset severe interstitial lung disease, hypotonia, and failure to thrive. Lung disease included emphysematous changes, fibrosis, and accumulation of cholesterol granulomas in the alveoli and interstitium. One patient underwent lung transplantation at 8 years of age. Additional features included intracranial calcifications, leukoencephalopathy (1 patient), intracranial aneurysms (2 sibs), hepatic cirrhosis or dysfunction of the liver, intestinal malrotation (2 patients), hypertension, and variable renal abnormalities, including renal artery stenosis, proteinuria, focal segmental glomerulosclerosis, and vesicoureteral reflux. Some patients had nonspecific dysmorphic features, such as frontal bossing, deep-set eyes, full cheeks, micrognathia, and small nose. Three patients had skeletal anomalies, including pectus excavatum, hyperextensibility, scoliosis, and arachnodactyly. Some patients had mild motor delay in infancy, but cognition was not impaired. Three patients died between ages 8 and 10 years of ruptured aneurysm, posttransplantion complications, and cardiac arrest, respectively. Inheritance Rajab et al. (2009) suggested autosomal recessive inheritance of the disorder in the Omani families because the parents in each family were first cousins and both girls and boys were affected. Mapping By genomewide and fine-mapping analyses of the extended family members and affected individuals in the Omani families, Rajab et al. (2009) found linkage of the disorder (maximum lod of 6.17) at D2S351 and D2S2390 on chromosome 2q36.2. Molecular Genetics In a boy with RILDBC, Antonellis et al. (2018) identified compound heterozygous mutations in the FARSB gene (609690.0001 and 609690.0002). The mutations, which were found by whole-exome sequencing, segregated with the disorder in the family. Western blot analysis of patient cells showed a 97% reduction in the FARSB protein and a 66% reduction in the FARSA (602918) protein compared to controls, suggesting a severe reduction in phenylalanyl-tRNA synthetase activity. Antonellis et al. (2018) postulated a loss-of-function effect. In affected members of a large consanguineous Omani family with RILDBC, previously reported by Rajab et al. (2009), Zadjali et al. (2018) identified a homozygous missense mutation in the FARSB gene (E285K; 609690.0003). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Western blot analysis of patient cells showed that the FARSB mutant protein was expressed at normal levels. Additional functional studies were not performed, but molecular modeling suggested that the mutation occurs in a domain involved in editing activity. In 5 patients from 4 unrelated families with RILDBC, Xu et al. (2018) identified biallelic mutations in the FARSB gene (see, e.g., 609690.0004-609690.0008). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Analysis of cells derived from 1 patient who carried a missense and a splice site mutation (609690.0004 and 609690.0005) showed decreased protein levels of FARSB and FARSA, but overall protein synthesis was not impaired, suggesting that the disorder results from a different mechanism. Functional studies and studies of patient cells were not performed for the other identified variants, all of which were missense, but molecular modeling predicted that they would affect protein structure. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature Weight \- Thin build Other \- Failure to thrive HEAD & NECK Head \- Microcephaly (in some patients) Face \- Dysmorphic facial features (in some patients) \- Prominent cheeks Eyes \- Deep-set eyes Mouth \- High-arched palate CARDIOVASCULAR Vascular \- Pulmonary hypertension \- Portal hypertension RESPIRATORY \- Tachypnea \- Respiratory insufficiency \- Chronic cough Lung \- Interstitial lung disease \- Emphysema \- Fibrosis \- Cholesterol-laden granulomas ABDOMEN External Features \- Ascites Liver \- Liver dysfunction \- Hepatic steatosis \- Cirrhosis \- Bile duct proliferation \- Portal hypertension \- Cholestasis Gastrointestinal \- Poor feeding \- Gastroesophageal reflux \- Vomiting GENITOURINARY External Genitalia (Male) \- Small phallus \- Small scrotum Kidneys \- Renal echogenicity SKELETAL \- Osteopenia \- Rickets \- Joint laxity MUSCLE, SOFT TISSUES \- Hypotonia \- Ascites \- Inguinal hernia NEUROLOGIC Central Nervous System \- Delayed development, motor, mild (in some patients) \- Seizures (in some patients) \- Abnormal periventricular white matter \- Basal ganglia echogenicity \- Intracranial calcifications \- Intracranial aneurysm \- Cerebral atrophy HEMATOLOGY \- Anemia \- Pancytopenia \- Coagulation defects PRENATAL MANIFESTATIONS Amniotic Fluid \- Oligohydramnios LABORATORY ABNORMALITIES \- Hypoalbuminemia \- Abnormal liver enzymes \- Hypocalcemia \- Vitamin D deficiency \- Vitamin A deficiency MISCELLANEOUS \- Onset in infancy \- Highly variable phenotype MOLECULAR BASIS \- Caused by mutation in the phenylalanine-tRNA synthetase, beta subunit gene (FARSB, 609690.0001 ) ▲ 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	RAJAB INTERSTITIAL LUNG DISEASE WITH BRAIN CALCIFICATIONS	c3150910	29,807	omim	https://www.omim.org/entry/613658	2019-09-22T15:58:01	{"omim": ["613658"], "orphanet": ["178506"], "synonyms": ["NEURODEVELOPMENTAL DISORDER WITH BRAIN, LIVER, AND LUNG ABNORMALITIES, FORMERLY", "Alternative titles", "DEVELOPMENTAL DELAY, SMALL STATURE, MICROCEPHALY, AND BRAIN CALCIFICATIONS, FORMERLY", "RAJAB SYNDROME"]}
Human disease Hidradenitis suppurativa Other namesAcne inversa, apocrine acne, Verneuil's disease, Velpeau’s disease[1] Hidradenitis suppurativa (stage II) in the left armpit. This is a very mild case of HS. SpecialtyDermatology SymptomsMultiple inflamed and swollen skin lesions[2] Usual onsetYoung adulthood[2] DurationLong-term[2] TypesStage I, II, III[1] CausesUnknown[3] Diagnostic methodBased on symptoms[2] Differential diagnosisAcne, acne conglobata, pilonidal cysts[2] TreatmentWarm baths, laser therapy, surgery[2][4] MedicationAntibiotics, immunosuppressive medication[2] Frequency1–4% of people, when mild cases are included[2][3] DeathsRare[1] Hidradenitis Suppurativa Stage III. Inflamed lesion. Hidradenitis Suppurativa. This lesion is about 4 inches across. Hidradenitis Suppurativa Stage III. Open lesions are extremely painful. Hidradenitis Suppurativa can take the form of growths on the skin that are extremely painful and debilitating. Hidradenitis suppurativa (HS), sometimes known as acne inversa or Verneuil's disease, is a long-term rheumatological condition characterized by the occurrence of inflamed and swollen lumps.[2][3] These are typically painful and break open, releasing fluid or pus.[3] The areas most commonly affected are the underarms, under the breasts, and the groin.[1] Scar tissue remains after healing.[1] The exact cause is usually unclear but believed to involve a combination of genetic and environmental factors.[3] About a third of people with the disease have an affected family member.[3] Other risk factors include obesity and smoking.[3] The condition is not caused by an infection, poor hygiene, or the use of deodorant.[3][4] Instead, it is believed to be caused by hair follicles that are near apocrine sweat glands being blocked, which in turn causes inflammation in the sweat glands.[1][3] Diagnosis is based on the symptoms.[2] There is no known cure.[4] Warm baths may be tried in those with mild disease.[4] Cutting open the lesions to allow them to drain does not result in significant benefit.[2] While antibiotics are commonly used, evidence for their use is poor.[4] Immunosuppressive medication may also be tried.[2] In those with more severe disease, laser therapy or surgery to remove the affected skin may be carried out.[2] Rarely, a skin lesion may develop into skin cancer.[3] If mild cases of HS are included, then the estimate of its frequency is from one to four percent of the population.[2][3] Women are three times more likely to be diagnosed with it than men.[2] Onset is typically in young adulthood and may become less common after fifty years old.[2] It was first described some time between 1833 and 1839 by French anatomist Alfred Velpeau.[1][5] Hidradenitis Suppurativa Stage III on abdomen. Skin is red and inflamed, constantly draining a malodorous blood/pus mixture. Pain is severe. ## Contents * 1 Causes * 1.1 Triggering factors * 1.2 Predisposing factors * 2 Diagnosis * 2.1 Stages * 2.1.1 Hurley's staging system * 2.1.2 Sartorius staging system * 3 Treatment * 3.1 Lifestyle * 3.2 Medication * 3.3 Surgery * 3.4 Laser hair removal * 4 Prognosis * 4.1 Potential complications * 5 History * 5.1 Other names * 5.2 Histology * 6 Terminology * 7 References * 8 External links ## Causes[edit] The cause of hidradenitis suppurativa remains unknown, and experts disagree over proposed causes.[6] The condition probably results from a combination of genetic and environmental factors.[3] Lesions occur in any body areas with hair follicles, although areas such as the axilla, groin, and perianal region are more commonly involved. This theory includes most of the following potential indicators:[7] * Post-pubescent individuals[8] * Blocked hair follicles or blocked apocrine sweat glands * Excessive sweating * Androgen dysfunction * Genetic disorders that alter cell structure * Patients with more advanced cases may find exercise intolerably painful, which may increase the rate of obesity among sufferers. The historical understanding of the disease suggests dysfunctional apocrine glands[9] or dysfunctional hair follicles,[10] possibly triggered by a blocked gland, which creates inflammation, pain, and a swollen lesion. Hidradenitis Suppurativa Stage III ### Triggering factors[edit] Several triggering factors should be taken into consideration: * Obesity[11] is an exacerbating rather than a triggering factor,[12] through mechanical irritation, occlusion, and skin maceration. * Tight clothing,[11] and clothing made of heavy, non-breathable materials.[13] * Deodorants, depilation products, shaving of the affected area – their association with HS is still an ongoing debate amongst researchers.[14] * Drugs, in particular oral contraceptive pills[15] and lithium.[16] * Hot and especially humid climates.[17] ### Predisposing factors[edit] * Genetic factors:[12] an autosomal dominant inheritance pattern has been proposed.[18] * Endocrine factors: sex hormones, especially an excess of androgens, are thought to be involved, although the apocrine glands are not sensitive to these hormones.[19] Women often have outbreaks before their menstrual period and after pregnancy; HS severity usually decreases during pregnancy and after menopause. Some cases have been found to result from mutations in the NCSTN, PSEN1 or PSENEN genes. The genes produce proteins that are all components of a complex called gamma- (γ-) secretase. This complex cuts apart (cleaves) many different proteins, which is an important step in several chemical signaling pathways. One of these pathways, known as Notch signaling, is essential for the normal maturation and division of hair follicle cells and other types of skin cells. Notch signaling is also involved in normal immune system function. Studies suggest that mutations in the NCSTN, PSEN1, or PSENEN gene impair Notch signaling in hair follicles. Although little is known about the mechanism, abnormal Notch signaling appears to promote the development of nodules and lead to inflammation in the skin.[20] ## Diagnosis[edit] ### Stages[edit] A case of hidradenitis suppurativa Micrograph of hidradenitis suppurativa. Sinus tracts [(A), arrow], active inflammation, and rupture [(B), asterisks] of the follicular epithelium with “floating” hair fragments [(B), arrow]. Subsequently, a secondary inflammatory response is induced with influx of numerous neutrophils [(C), arrows] and granulomatous foreign body reaction with giant cells [(C), asterisks].[21] Hidradenitis suppurativa presents itself in three stages.[9][22] Due to the large spectrum of clinical severity and the severe impact on quality of life, a reliable method for evaluating HS severity is needed.[citation needed] #### Hurley's staging system[edit] The Hurley's staging system was the first classification system proposed, and is still in use for the classification of patients with skin diseases (i.e., psoriasis, HS, acne). Hurley separated patients into three groups based largely on the presence and extent of cicatrization and sinuses. It has been used as a basis for clinical trials in the past and is a useful basis to approach therapy for patients. These three stages are based on Hurley's staging system, which is simple and relies on the subjective extent of the diseased tissue the patient has. Hurley's three stages of hidradenitis suppurativa are:[23] Stage Characteristics I Solitary or multiple isolated abscess formation without scarring or sinus tracts. (A few minor sites with rare inflammation; may be mistaken for acne.) II Recurrent abscesses, single or multiple widely separated lesions, with sinus tract formation. (Frequent inflammation restrict movement and may require minor surgery such as incision and drainage.) III Diffuse or broad involvement across a regional area with multiple interconnected sinus tracts and abscesses (Inflammation of sites to the size of golf balls, or sometimes baseballs; scarring develops, including subcutaneous tracts of infection – see fistula. Obviously, patients at this stage may be unable to function.) #### Sartorius staging system[edit] The Sartorius staging system is more sophisticated than Hurley's. Sartorius et al. suggested that the Hurley system is not sophisticated enough to assess treatment effects in clinical trials during research. This classification allows for better dynamic monitoring of the disease severity in individual patients. The elements of this staging system are:[24] * Anatomic regions involved (axilla, groin gluteal, or other region or inframammary region left or right) * Number and types of lesions involved (abscesses, nodules, fistulas or sinuses, scars, points for lesions of all regions involved) * The distance between lesions, in particular the longest distance between two relevant lesions (i.e., nodules and fistulas in each region or size if only one lesion present) * The presence of normal skin in between lesions (i.e., if all lesions are clearly separated by normal skin) Points are accumulated in each of the above categories, and added to give both a regional and total score. In addition, the authors recommend adding a visual analog scale for pain or using the dermatology life quality index (DLQI, or the 'skindex') when assessing HS.[25] ## Treatment[edit] Treatment depends upon presentation and severity of the disease. Due to the poorly studied nature of the disease, the effectiveness of the drugs and therapies listed below is unclear.[26] Possible treatments include the following: ### Lifestyle[edit] Warm baths may be tried in those with mild disease.[4] Weight loss and stopping smoking is also recommended.[2] ### Medication[edit] * Antibiotics: taken by mouth, these are used for their anti-inflammatory properties rather than to treat infection. Most effective is a combination of rifampicin and clindamycin given concurrently for 2–3 months. A few popular antibiotics include tetracycline, minocycline, and clindamycin.[27] Topical clindamycin has been shown to have an effect in double-blind placebo controlled studies.[28] * Corticosteroid injections. Also known as intralesional steroids: can be particularly useful for localized disease, if the drug can be prevented from escaping via the sinuses. * Antiandrogen therapy: hormonal therapy with antiandrogenic medications such as spironolactone, flutamide, cyproterone acetate, ethinylestradiol, finasteride, dutasteride, and metformin have been found to be effective in clinical studies.[29][30][31] However, the quality of available evidence is low and does not presently allow for robust evidence-based recommendations.[29][30] * Intravenous or subcutaneous infusion of anti-inflammatory (TNF inhibitors; anti-TNF-alpha) drugs such as infliximab, and etanercept.[32] This use of these drugs is not currently Food and Drug Administration (FDA) approved and is somewhat controversial, so may not be covered by insurance. * TNF inhibitor: Studies have supported that various TNF inhibitors have a positive effect on HS lesions.[33] Specifically adalimumab at weekly intervals is useful.[34] * Topical isotretinoin is usually ineffective in people with HS and is more commonly known as a medication for the treatment of acne vulgaris. Individuals affected by HS who responded to isotretinoin treatment tended to have milder cases of the condition.[35] ### Surgery[edit] When the process becomes chronic, wide surgical excision is the procedure of choice. Wounds in the affected area do not heal by secondary intention, and immediate or delayed application of a split-thickness skin graft is an option.[7] Another option is covering the defect with a perforator flap. With this technique the (mostly totally excised) defect is covered with tissue from an area nearby. For example, the axilla with a fully excised defect of 15 × 7 cm can be covered with a TAP flap (thoracodorsal artery perforator flap)[citation needed] ### Laser hair removal[edit] The 1064 nanometer wavelength laser for hair removal may aid in the treatment of HS.[36] A randomized control study has shown improvement in HS lesions with the use of an Nd:YAG laser.[37] ## Prognosis[edit] In stage III disease, as classified by the Hurley's staging system, fistulae left undiscovered, undiagnosed, or untreated, can rarely lead to the development of squamous cell carcinoma in the anus or other affected areas.[38][39] Other stage III chronic sequelae may also include anemia, multilocalized infections, amyloidosis, and arthropathy. Stage III complications have been known to lead to sepsis, but clinical data is still uncertain. ### Potential complications[edit] * Contractures and reduced mobility of the lower limbs and axillae due to fibrosis and scarring occur. Severe lymphedema may develop in the lower limbs. * Local and systemic infections (meningitis, bronchitis, pneumonia, etc.), are seen, which may even progress to sepsis. * Interstitial keratitis * Anal, rectal, or urethral fistulae[40] * Normochromic or hypochromic anemia[41] * People with HS may be at increased risk for autoimmune disorders including ankylosing spondylitis, rheumatoid arthritis, and psoriatic arthritis.[42] * Squamous cell carcinoma: this has been found on rare occasions in chronic hidradenitis suppurativa of the anogenital region.[43] The mean time to the onset of this type of lesion is 10 years or more and the tumors are usually highly aggressive. * Tumors of the lung and oral cavity, and liver cancer.[44] * Hypoproteinemia and amyloidosis, which can lead to kidney failure and death[45] * Seronegative and usually asymmetric arthropathy: pauciarticular arthritis, polyarthritis/polyarthralgia syndrome[46] ## History[edit] * From 1833 to 1839 in a series of three publications, Velpeau identified and described a disease we now know as hidradenitis suppurativa.[47] * In 1854, Verneuil described hidradenitis suppurativa as hidrosadénite Phlegmoneuse. This is how HS obtained its alternate name "Verneuil's disease".[48] * In 1922, Schiefferdecker hypothesized a pathogenic link between "acne inversa" and human sweat glands.[49] * In 1956, Pillsbury et al.[50] coined the term follicular occlusion triad for the common association of hidradenitis suppurativa, acne conglobata and dissecting cellulitis of the scalp. Modern clinical research still employs Pillsbury's terminology for these conditions' descriptions.[51] * In 1975, Plewig and Kligman, following Pillsbury's research path, modified the "acne triad", replacing it with the "acne tetrad: acne triad, plus pilonidal sinus".[52] Plewig and Kligman's research follows in Pillsbury's footsteps, offering explanations of the symptoms associated with hidradenitis suppurativa. * In 1989, Plewig and Steger's research led them to rename hidradenitis suppurativa, calling it "acne inversa" – which is not still used today in medical terminology, although some individuals still use this outdated term.[53] A surgeon from Paris, Velpeau described an unusual inflammatory process with formation of superficial axillary, submammary, and perianal abscesses, in a series of three publications from 1833 to 1839. One of his colleagues also located in Paris, named Verneuil, coined the term hidrosadénite phlegmoneuse about 15 years later. This name for the disease reflects the former pathogenetic model of acne inversa, which is considered inflammation of sweat glands as the primary cause of hidradenitis suppurativa. In 1922, Schiefferdecker suspected a pathogenic association between acne inversa and apocrine sweat glands. In 1956 Pillsbury postulated follicular occlusion as the cause of acne inversa, which they grouped together with acne conglobata and perifolliculitis capitis abscendens et suffodiens ("dissecting cellulitis of the scalp") as the "acne triad". Plewig and Kligman added another element to their acne triad, pilonidal sinus. Plewig et al. noted that this new "acne tetrad" includes all the elements found in the original "acne triad", in addition to a fourth element, pilonidal sinus. In 1989, Plewig and Steger introduced the term "acne inversa", indicating a follicular source of the disease and replacing older terms such as "Verneuil disease". Author Year Findings Velpeau 1839 First description of the hidradenitis suppurativa Verneuil 1854 "Hidrosadénite phlegmoneuse" Pillsbury 1956 Acne triad (hidradenitis suppurativa, perifolliculitis capitis abscendens et suffodiens, acne congoblata) Plewig & Kligman 1975 Acne tetrad (acne triad + pilonidal sinus) Plewig & Steger 1989 Acne inversa ### Other names[edit] Hidradenitis suppurativa has been referred to by multiple names in the literature, as well as in various cultures. Some of these are also used to describe different diseases, or specific instances of this disease.[22] * Acne conglobata – not really a synonym – this is a similar process but in classic acne areas of chest and back * Acne inversa – a proposed new term[54][55] which has not gained widespread favor.[56] * Apocrine acne – an outdated term based on the disproven[citation needed] concept that apocrine glands are primarily involved, though many do suffer with apocrine gland infection * Apocrinitis – another outdated term based on the same thesis * Fox-den disease – a term not used in medical literature, based on the deep fox den–like sinuses * Hidradenitis supportiva – a misspelling * Pyodermia fistulans significa – now considered archaic * Verneuil's disease – recognizing the surgeon whose name is most often associated with the disorder as a result of his 1854–1865 studies[57] ### Histology[edit] Author Year Major Features Plewig & Steger[53] 1989 Initial hyperkeratosis of the follicular infundibulum. Bacterial super-infection and follicle rupture. Granulomatous inflammatory reaction of the connective tissue. Apocrine and eccrine sweat glands secondarily involved. Yu & Cook[58] 1990 Cysts and sinus tracts lined with epithelium, in part with hair shafts. Inflammation of apocrine sweat glands only if eccrine sweat glands and hair follicles are also inflamed. Boer & Weltevreden[59] 1996 Primary inflammation of the follicular infundibulum. Apocrine sweat glands are secondarily involved. ## Terminology[edit] Although hidradenitis suppurativa is often referred to as acne inversa, it is not a form of acne and lacks the core defining features of acne such as the presence of closed comedones and increased sebum production.[60] ## References[edit] 1. ^ a b c d e f g "Hidradenitis Suppurativa". NORD (National Organization for Rare Disorders). 2012. Archived from the original on 19 February 2017. Retrieved 26 October 2017. 2. ^ a b c d e f g h i j k l m n o p q Jemec GB (January 2012). "Clinical practice. Hidradenitis suppurativa". The New England Journal of Medicine. 366 (2): 158–64. doi:10.1056/NEJMcp1014163. PMID 22236226. 3. ^ a b c d e f g h i j k l "Hidradenitis suppurativa". Genetics Home Reference. December 2013. Archived from the original on 5 September 2017. Retrieved 27 October 2017. 4. ^ a b c d e f "Hidradenitis suppurativa". rarediseases.info.nih.gov. 2017. Archived from the original on 28 July 2017. Retrieved 27 October 2017. 5. ^ Jemec G, Revuz J, Leyden JJ (2006). Hidradenitis Suppurativa. Springer Science & Business Media. p. 5. ISBN 9783540331018. Archived from the original on 28 October 2017. 6. ^ Medline Plus (2012). "Hidradenitis suppurativa". U.S. National Library of Medicine. Archived from the original on 16 September 2012. Retrieved 19 September 2012. 7. ^ a b Schawartz's principles of surgery, 8th edition, self assessment an board review, chapter 15, the skin and subcutaneous tissue, question 16 8. ^ Mayo Clinic Staff (2012). "Definition". Mayo Clinic. Archived from the original on 10 September 2012. Retrieved 19 September 2012. 9. ^ a b DermNet acne/hidradenitis-suppurativa 10. ^ "HSF – What is Hidradenitis Suppurativa? What is HS?". Archived from the original on 6 July 2007. Retrieved 8 July 2007. 11. ^ a b Slade DE, Powell BW, Mortimer PS (July 2003). "Hidradenitis suppurativa: pathogenesis and management". British Journal of Plastic Surgery. 56 (5): 451–61. doi:10.1016/S0007-1226(03)00177-2. PMID 12890458. 12. ^ a b Jemec GBE. Body weight in hidradenitis suppurativa. In: Marks R, Plewig G, editors. Acne and Related disorders. London: Martin Dunitz; 1989. pp. 375–6. 13. ^ König A, Lehmann C, Rompel R, Happle R (1999). "Cigarette smoking as a triggering factor of hidradenitis suppurativa". Dermatology. 198 (3): 261–4. doi:10.1159/000018126. PMID 10393449. S2CID 25343489. 14. ^ Morgan WP, Hughes LE (December 1979). "The distribution, size and density of the apocrine glands in hidradenitis suppuritiva". 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"Androgen metabolism by isolated human axillary apocrine glands in hidradenitis suppurativa". The British Journal of Dermatology. 125 (4): 304–8. doi:10.1111/j.1365-2133.1991.tb14162.x. PMID 1954117. S2CID 34410437. 20. ^ Reference, Genetics Home. "hidradenitis suppurativa". Genetics Home Reference. Archived from the original on 5 September 2017. Retrieved 5 September 2017. 21. ^ 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. 22. ^ a b "HS-USA :: What is Hidradenitis Suppurativa?". Archived from the original on 17 June 2013. Retrieved 20 July 2013. 23. ^ Hurley HJ. Axillary hyperhidrosis, apocrine bromhidrosis, hidradenitis suppurativa, and familial benign pemphigus: surgical approach. In: Roenigk RK, Roenigk HH, editors. Dermatologic surgery. Marcel Dekker, New York, 1989, pp. 729–739. 24. ^ Sartorius K, Lapins J, Emtestam L, Jemec GB (July 2003). "Suggestions for uniform outcome variables when reporting treatment effects in hidradenitis suppurativa". The British Journal of Dermatology. 149 (1): 211–3. doi:10.1046/j.1365-2133.2003.05390.x. PMID 12890229. S2CID 46142606. 25. ^ Wolkenstein P, Loundou A, Barrau K, Auquier P, Revuz J (April 2007). "Quality of life impairment in hidradenitis suppurativa: a study of 61 cases". Journal of the American Academy of Dermatology. 56 (4): 621–3. doi:10.1016/j.jaad.2006.08.061. PMID 17097366. 26. ^ Ingram JR, Woo PN, Chua SL, Ormerod AD, Desai N, Kai AC, et al. (May 2016). "Interventions for hidradenitis suppurativa: a Cochrane systematic review incorporating GRADE assessment of evidence quality". The British Journal of Dermatology. 174 (5): 970–8. doi:10.1111/bjd.14418. PMC 5021164. PMID 26801356. 27. ^ Scheinfeld N (April 2013). "Hidradenitis suppurativa: A practical review of possible medical treatments based on over 350 hidradenitis patients". Dermatology Online Journal. 19 (4): 1. PMID 24021361. 28. ^ Clemmensen OJ (June 1983). "Topical treatment of hidradenitis suppurativa with clindamycin". International Journal of Dermatology. 22 (5): 325–8. doi:10.1111/j.1365-4362.1983.tb02150.x. PMID 6347922. S2CID 46661288. 29. ^ a b Nikolakis, Georgios; Kyrgidis, Athanassios; Zouboulis, Christos C. (2019). "Is There a Role for Antiandrogen Therapy for Hidradenitis Suppurativa? A Systematic Review of Published Data". American Journal of Clinical Dermatology. 20 (4): 503–513. doi:10.1007/s40257-019-00442-w. ISSN 1175-0561. PMID 31073704. S2CID 149443722. 30. ^ a b Goldburg, Samantha R.; Strober, Bruce E.; Payette, Michael J. (2019). "Part 2. Current and emerging treatments for hidradenitis suppurativa". Journal of the American Academy of Dermatology. 82 (5): 1061–1082. doi:10.1016/j.jaad.2019.08.089. ISSN 0190-9622. PMID 31604100. 31. ^ Student, Sebastian; Hejmo, Tomasz; Poterała-Hejmo, Aleksandra; Leśniak, Aleksandra; Bułdak, Rafał (2020). "Anti-androgen hormonal therapy for cancer and other diseases". European Journal of Pharmacology. 866: 172783. doi:10.1016/j.ejphar.2019.172783. ISSN 0014-2999. PMID 31712062. 32. ^ Cusack C, Buckley C (April 2006). "Etanercept: effective in the management of hidradenitis suppurativa". The British Journal of Dermatology. 154 (4): 726–9. doi:10.1111/j.1365-2133.2005.07067.x. PMID 16536817. S2CID 23743987. 33. ^ Haslund P, Lee RA, Jemec GB (November 2009). "Treatment of hidradenitis suppurativa with tumour necrosis factor-alpha inhibitors". Acta Dermato-Venereologica. 89 (6): 595–600. doi:10.2340/00015555-0747. PMID 19997689. 34. ^ Ingram JR (May 2017). "Interventions for Hidradenitis Suppurativa: Updated Summary of an Original Cochrane Review". JAMA Dermatology. 153 (5): 458–459. doi:10.1001/jamadermatol.2017.0432. PMID 28355440. 35. ^ Nickle SB, Peterson N, Peterson M (April 2014). "Updated Physician's Guide to the Off-label Uses of Oral Isotretinoin". The Journal of Clinical and Aesthetic Dermatology. 7 (4): 22–34. PMC 3990537. PMID 24765227. 36. ^ Scheinfeld N (April 2013). "Hidradenitis suppurativa: A practical review of possible medical treatments based on over 350 hidradenitis patients". Dermatology Online Journal. 19 (4): 1. PMID 24021361. Archived from the original on 6 March 2014. Retrieved 4 March 2014. 37. ^ Xu LY, Wright DR, Mahmoud BH, Ozog DM, Mehregan DA, Hamzavi IH (January 2011). "Histopathologic study of hidradenitis suppurativa following long-pulsed 1064-nm Nd:YAG laser treatment". Archives of Dermatology. 147 (1): 21–8. doi:10.1001/archdermatol.2010.245. PMID 20855672. 38. ^ Talmant JC, Bruant-Rodier C, Nunziata AC, Rodier JF, Wilk A (February 2006). "[Squamous cell carcinoma arising in Verneuil's disease: two cases and literature review]". Annales de Chirurgie Plastique et Esthétique (in French). 51 (1): 82–6. doi:10.1016/j.anplas.2005.11.002. PMID 16488526. 39. ^ Short KA, Kalu G, Mortimer PS, Higgins EM (September 2005). "Vulval squamous cell carcinoma arising in chronic hidradenitis suppurativa". Clinical and Experimental Dermatology. 30 (5): 481–3. doi:10.1111/j.1365-2230.2005.01875.x. PMID 16045671. S2CID 33438993. 40. ^ Hurley HJJ. Apocrine glands. New York: McGraw Hill; 1979. 41. ^ Tennant F, Bergeron JR, Stone OJ, Mullins JF (August 1968). "Anemia associated with hidradenitis suppurativa". Archives of Dermatology. 98 (2): 138–40. doi:10.1001/archderm.98.2.138. PMID 5667225. 42. ^ Schneeweiss MC, Kim SC, Schneeweiss S, Rosmarin D, Merola JF (2020). "Risk of inflammatory arthritis after a new diagnosis of hidradenitis suppurativa". JAMA Dermatology. 156 (3): 342–345. doi:10.1001/jamadermatol.2019.4590. PMC 6990727. PMID 31968066. 43. ^ Williams ST, Busby RC, DeMuth RJ, Nelson H (May 1991). "Perineal hidradenitis suppurativa: presentation of two unusual complications and a review". Annals of Plastic Surgery. 26 (5): 456–62. doi:10.1097/00000637-199105000-00008. PMID 1952719. 44. ^ Lapins J, Ye W, Nyrén O, Emtestam L (June 2001). "Incidence of cancer among patients with hidradenitis suppurativa". Archives of Dermatology. 137 (6): 730–4. PMID 11405761. 45. ^ Moschella SL (October 1966). "Hidradenitis suppurativa. Complications resulting in death". JAMA. 198 (1): 201–3. doi:10.1001/jama.198.1.201. PMID 5953172. 46. ^ Vasey FB, Fenske NA, Clement GB, Bridgeford PH, Germain BF, Espinoza LR (1984). "Immunological studies of the arthritis of acne conglobata and hidradenitis suppurativa". Clinical and Experimental Rheumatology. 2 (4): 309–11. PMID 6241861. 47. ^ Velpeau A. Aissele. In: Bechet Jeune Z: Dictionnaire de médecine, on Repertoire Générale des Sciences Medicals sous le Rapport Theorique et Pratique. 1839. 48. ^ Verneuil AS (1854). "Etudes sur les tumeurs de la peau et quelques maladies de glandes sudoripares" [Studies on skin tumors; some diseases of the sweat glands]. Archives of General Medicine (in French). 94: 693–705. 49. ^ Schiefferdecker B (1922). Die Hautdrüsen der Menschen und der Säugetiere, ihre histologische und rassenanatomische Bedeutung sowie die muscularis sexualis [The skin glands of humans and mammals, their histological and anatomical racial meaning and muscularis sexualis]. Stuttgart: Schweizerbart E.[page needed] 50. ^ Pillsbury DM, Shelley WB, Kligmann AM (1956). "Bacterial infections of the skin". In Pillsbury DM (ed.). Dermatoloy (1st ed.). Philadelphia. pp. 482–9. 51. ^ Triads in Dermatology; Prachi G Agrawal, Uday S Khopkar, [...], and Sunil N Mishra; J Dermatol. 2013 Sep–Oct; 58(5): 346–351 52. ^ Plewig G, Kligman AM (1975). "Acne Conglobata". In Plewig G, Kligman AM (eds.). Acne: Morphogenesis and Treatment. pp. 168–203. doi:10.1007/978-3-642-96246-2_11. ISBN 978-3-642-96246-2. 53. ^ a b Plewig G, Steger M (1989). "Acne inversa (alias acne triad, acne tetrad or hidradenitis suppurativa)". In Marks R, Plewig G (eds.). Acne and Related Disorders. London: Martin Dunitz. pp. 345–57. 54. ^ Sellheyer K, Krahl D (July 2005). ""Hidradenitis suppurativa" is acne inversa! An appeal to (finally) abandon a misnomer". International Journal of Dermatology. 44 (7): 535–40. doi:10.1111/j.1365-4632.2004.02536.x. PMID 15985019. S2CID 34144101. 55. ^ Bazex J, Bayle P, San B (March 2007). "Hidradenitis suppurativa is acne inversa". International Journal of Dermatology. 46 (3): 330, author reply 330–2. doi:10.1111/j.1365-4632.2007.02872.x. PMID 17343599. S2CID 43108078. 56. ^ Scheinfeld N (December 2006). "Hidradenitis should not be renamed acne inversa". Dermatology Online Journal. 12 (7): 6. PMID 17459292. 57. ^ Verneuil AS (1854). "Etudes sur les tumor de la peau". Arch Gen Med (in French). 94: 693. 58. ^ Yu CC, Cook MG (June 1990). "Hidradenitis suppurativa: a disease of follicular epithelium, rather than apocrine glands". The British Journal of Dermatology. 122 (6): 763–9. doi:10.1111/j.1365-2133.1990.tb06264.x. PMID 2369556. S2CID 8857181. 59. ^ Boer J, Weltevreden EF (November 1996). "Hidradenitis suppurativa or acne inversa. A clinicopathological study of early lesions". The British Journal of Dermatology. 135 (5): 721–5. doi:10.1111/j.1365-2133.1996.tb03880.x. PMID 8977671. 60. ^ Dessinioti C, Katsambas A, Antoniou C (May–June 2014). "Hidradenitis suppurrativa (acne inversa) as a systemic disease". Clinics in Dermatology. 32 (3): 397–408. doi:10.1016/j.clindermatol.2013.11.006. PMID 24767187. ## External links[edit] * Medline: What is Hidradenitis Suppurativa? * Hidradenitis Suppurativa (2004) Prof J. Revuz Classification D * ICD-10: L73.2 * ICD-9-CM: 705.83 * MeSH: D017497 * DiseasesDB: 5892 External resources * eMedicine: emerg/259 med/2717 derm/892 * Patient UK: Hidradenitis suppurativa * v * t * e Disorders of skin appendages Nail * thickness: Onychogryphosis * Onychauxis * color: Beau's lines * Yellow nail syndrome * Leukonychia * Azure lunula * shape: Koilonychia * Nail clubbing * behavior: Onychotillomania * Onychophagia * other: Ingrown nail * Anonychia * ungrouped: Paronychia * Acute * Chronic * Chevron nail * Congenital onychodysplasia of the index fingers * Green nails * Half and half nails * Hangnail * Hapalonychia * Hook nail * Ingrown nail * Lichen planus of the nails * Longitudinal erythronychia * Malalignment of the nail plate * Median nail dystrophy * Mees' lines * Melanonychia * Muehrcke's lines * Nail–patella syndrome * Onychoatrophy * Onycholysis * Onychomadesis * Onychomatricoma * Onychomycosis * Onychophosis * Onychoptosis defluvium * Onychorrhexis * Onychoschizia * Platonychia * Pincer nails * Plummer's nail * Psoriatic nails * Pterygium inversum unguis * Pterygium unguis * Purpura of the nail bed * Racquet nail * Red lunulae * Shell nail syndrome * Splinter hemorrhage * Spotted lunulae * Staining of the nail plate * Stippled nails * Subungual hematoma * Terry's nails * Twenty-nail dystrophy Hair Hair loss/ Baldness * noncicatricial alopecia: Alopecia * areata * totalis * universalis * Ophiasis * Androgenic alopecia (male-pattern baldness) * Hypotrichosis * Telogen effluvium * Traction alopecia * Lichen planopilaris * Trichorrhexis nodosa * Alopecia neoplastica * Anagen effluvium * Alopecia mucinosa * cicatricial alopecia: Pseudopelade of Brocq * Central centrifugal cicatricial alopecia * Pressure alopecia * Traumatic alopecia * Tumor alopecia * Hot comb alopecia * Perifolliculitis capitis abscedens et suffodiens * Graham-Little syndrome * Folliculitis decalvans * ungrouped: Triangular alopecia * Frontal fibrosing alopecia * Marie Unna hereditary hypotrichosis Hypertrichosis * Hirsutism * Acquired * localised * generalised * patterned * Congenital * generalised * localised * X-linked * Prepubertal Acneiform eruption Acne * Acne vulgaris * Acne conglobata * Acne miliaris necrotica * Tropical acne * Infantile acne/Neonatal acne * Excoriated acne * Acne fulminans * Acne medicamentosa (e.g., steroid acne) * Halogen acne * Iododerma * Bromoderma * Chloracne * Oil acne * Tar acne * Acne cosmetica * Occupational acne * Acne aestivalis * Acne keloidalis nuchae * Acne mechanica * Acne with facial edema * Pomade acne * Acne necrotica * Blackhead * Lupus miliaris disseminatus faciei Rosacea * Perioral dermatitis * Granulomatous perioral dermatitis * Phymatous rosacea * Rhinophyma * Blepharophyma * Gnathophyma * Metophyma * Otophyma * Papulopustular rosacea * Lupoid rosacea * Erythrotelangiectatic rosacea * Glandular rosacea * Gram-negative rosacea * Steroid rosacea * Ocular rosacea * Persistent edema of rosacea * Rosacea conglobata * variants * Periorificial dermatitis * Pyoderma faciale Ungrouped * Granulomatous facial dermatitis * Idiopathic facial aseptic granuloma * Periorbital dermatitis * SAPHO syndrome Follicular cysts * "Sebaceous cyst" * Epidermoid cyst * Trichilemmal cyst * Steatocystoma * simplex * multiplex * Milia Inflammation * Folliculitis * Folliculitis nares perforans * Tufted folliculitis * Pseudofolliculitis barbae * Hidradenitis * Hidradenitis suppurativa * Recurrent palmoplantar hidradenitis * Neutrophilic eccrine hidradenitis Ungrouped * Acrokeratosis paraneoplastica of Bazex * Acroosteolysis * Bubble hair deformity * Disseminate and recurrent infundibulofolliculitis * Erosive pustular dermatitis of the scalp * Erythromelanosis follicularis faciei et colli * Hair casts * Hair follicle nevus * Intermittent hair–follicle dystrophy * Keratosis pilaris atropicans * Kinking hair * Koenen's tumor * Lichen planopilaris * Lichen spinulosus * Loose anagen syndrome * Menkes kinky hair syndrome * Monilethrix * Parakeratosis pustulosa * Pili (Pili annulati * Pili bifurcati * Pili multigemini * Pili pseudoannulati * Pili torti) * Pityriasis amiantacea * Plica neuropathica * Poliosis * Rubinstein–Taybi syndrome * Setleis syndrome * Traumatic anserine folliculosis * Trichomegaly * Trichomycosis axillaris * Trichorrhexis (Trichorrhexis invaginata * Trichorrhexis nodosa) * Trichostasis spinulosa * Uncombable hair syndrome * Wooly hair nevus Sweat glands Eccrine * Miliaria * Colloid milium * Miliaria crystalline * Miliaria profunda * Miliaria pustulosa * Miliaria rubra * Occlusion miliaria * Postmiliarial hypohidrosis * Granulosis rubra nasi * Ross’ syndrome * Anhidrosis * Hyperhidrosis * Generalized * Gustatory * Palmoplantar Apocrine * Body odor * Chromhidrosis * Fox–Fordyce disease Sebaceous * Sebaceous hyperplasia [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Hidradenitis suppurativa	c0162836	29,808	wikipedia	https://en.wikipedia.org/wiki/Hidradenitis_suppurativa	2021-01-18T18:58:35	{"gard": ["6658"], "mesh": ["D017497"], "umls": ["C0162836"], "icd-9": ["705.83"], "wikidata": ["Q341999"]}
Licking eyeballs may cause viral conjunctivitis (pictured) Oculolinctus, also known as "worming" or eyeball-licking fetishism, refers to the paraphilic practice of licking eyeballs for erotic gratification. In mid-2013, English-language newspapers reported that this fetish had allegedly become popular in Japan, where it was referred to as Gankyū name purei (眼球舐めプレイ, "eyeball licking play").[1] However, other media have reported that the existence of this practice is a hoax based on a story in a Japanese tabloid[2][3] and many of the originally reporting articles were corrected[4] or retracted[5] as being possibly a hoax. ## Characteristics[edit] In 2013, oculolinctus reportedly became popular among teenagers in Japan, causing a significant rise in eye infections. According to a retracted article by The Guardian, eyeball-licking was "seen as a new second-base; the thing you graduate to when kissing gets boring", possibly due to it being featured in a music video by the Japanese band Born.[5] Further reports, e.g. in an article by the Huffington Post later corrected as a possible hoax, showed an increase in Japanese schoolchildren wearing eyepatches due to eye infections arising from the act, with one school finding one third of 12-year-old students admitting to engaging in oculolinctus.[4] There are also accounts of this practice in the U.S. Virgin Islands.[6] ## Risks of licking an eyeball[edit] The practice is associated with significant health risks, as tongues are coated with a film of microorganisms. These microorganisms may cause infections in the eye such as conjunctivitis, herpes, chlamydia, corneal abrasions[5] and corneal ulcers.[7] Oral bacteria on the tongue can potentially enter corneal scratches caused by licking the eye, which then lead to infection.[8] Furthermore, there is also the risk of blindness from the resulting infections, as well as styes. The difference in bacteria between the eye and mouth is why it is no longer recommended to lick contact lenses before they are inserted into one's eye.[6] ## References[edit] 1. ^ 2013-06-07, 小学生に眼球なめ変態プレイが大流行 Archived 2015-06-10 at the Wayback Machine, 読めるモ 2. ^ "LICK THIS! Mark Schreiber". Archived from the original on 2013-10-06. Retrieved 2013-08-04. 3. ^ "Blind spot: How a hoax about eye licking went global". CNET. 4. ^ a b David Moye, 2013-06-12, "Eyeball Licking Causing Pinkeye In Japan", The Huffington Post (later corrected as a hoax) 5. ^ a b c Heritage, Stuart (14 June 2013). "Eyeball-licking: the fetish that is making Japanese teenagers sick". The Guardian. Retrieved 14 June 2013. 6. ^ a b Waxman, Olivia B. (14 June 2013). "Eyeball-Licking Fetish Isn't Just Disgusting, It Spreads Pink Eye". TIME. Retrieved 14 June 2013. 7. ^ Narcisse, Quenton (14 June 2013). "Eyeball Licking: Japan's Craziest New Fetish". Mashable. Retrieved 14 June 2013. 8. ^ Ashik Siddique, 2013-06-12, "Eyeball Licking ‘Oculolinctus’ Fetish Spreads Pink Eye Among Japanese Preteens", Medical Daily * v * t * e Sexual fetishism Actions, states * Aquaphilia * Autassassinophilia * Coprophilia * Cuckold / Cuckquean * Emetophilia * Erotic hypnosis * Erotic lactation * Erotic spanking * Exhibitionism * Forced seduction * Gaining and feeding * Medical fetishism * Omorashi * Paraphilic infantilism (adult baby) * Pregnancy * Smoking * Tickling * Total enclosure * Transvestic * Tightlacing * Tamakeri * Urolagnia * Vorarephilia * Wet and messy fetishism Body parts * Armpit * Breast * Belly * Buttocks * Eyeball * Fat * Feet * Hands * Height * Hair * Legs * Navels * Noses Clothing * Boots * Ballet boots * Boot worship * Thigh-high boots * Clothing * Corset * Diapers * Gloves * Pantyhose * Latex * Rubber and PVC * Shoes * Spandex * Underwear * Uniforms Objects * Balloons * Dolls * Latex and PVC * Robots * Spandex Controversial / illegal * Lust murder * Necrophilia * Rape fantasy * Zoophilia Culture / media * Artists * Fetish art * Fetish clubs * Fashion * Magazines * Models Race * Asian sexual fetishism * Ethnic pornography * Sexual racism Related topics * BDSM * FetLife * International Fetish Day * Kink * Leather subculture * Leather Pride flag * Sexual roleplay * Book * Category [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Oculolinctus	None	29,809	wikipedia	https://en.wikipedia.org/wiki/Oculolinctus	2021-01-18T19:07:57	{"wikidata": ["Q8015448"]}
Hereditary lymphedema type II is a primary lymphedema that results from abnormal transport of lymph fluid. Individuals with this condition usually develop swelling in the lower legs and feet during puberty. Some affected individuals develop a non-contagious skin infection called cellulitis, which can further damage the lymphatic vessels (the thin tubes that carry lymph fluid). While the cause of hereditary lymphedema type II is unknown, it is thought to be genetic because it tends to run in families. It appears to have 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	Hereditary lymphedema type II	c0238261	29,810	gard	https://rarediseases.info.nih.gov/diseases/3324/hereditary-lymphedema-type-ii	2021-01-18T18:00:02	{"mesh": ["C562467"], "omim": ["153200"], "orphanet": ["90186"], "synonyms": ["Meige disease", "Meige lymphedema", "Lymphedema, late-onset", "Lymphedema praecox", "Lymphedema, hereditary, II", "Lymphedema hereditary type 2"]}
Charcot-Marie-Tooth disease type 1B (CMT1B) is a form of CMT1 (see this term), caused by mutations in the MPZ gene (1q22), that presents with the manifestations of peripheral neuropathy (distal muscle weakness and atrophy, foot deformities and sensory loss). The phenotype is variable depending on the particular mutation. Two distinct presentations have been described: (1) an early infantile onset severe phenotype with delayed walking and motor nerve conduction velocities (MNCV) <10 m/s, often referred to as Dejerine-Sottas syndrome (see this term), or (2) a much later onset phenotype (>age 40), with normal or mildly slowed MNCV and more frequent hearing loss and pupillary abnormalities. CMT1B can also cause the classical CMT phenotype in about 15% of total CMT1B cases. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Charcot-Marie-Tooth disease type 1B	c0270912	29,811	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=101082	2021-01-23T18:12:15	{"gard": ["1246"], "mesh": ["D002607"], "omim": ["118200"], "umls": ["C0270912"], "icd-10": ["G60.0"], "synonyms": ["CMT1B"]}
Hypervitaminosis A Forms of preformed vitamin A in the body SpecialtyToxicology Hypervitaminosis A refers to the toxic effects of ingesting too much preformed vitamin A (retinyl esters, retinol, and retinal). Symptoms arise as a result of altered bone metabolism and altered metabolism of other fat-soluble vitamins. Hypervitaminosis A is believed to have occurred in early humans, and the problem has persisted throughout human history. Toxicity results from ingesting too much preformed vitamin A from foods (such as fish or animal liver), supplements, or prescription medications and can be prevented by ingesting no more than the recommended daily amount. Diagnosis can be difficult, as serum retinol is not sensitive to toxic levels of vitamin A, but there are effective tests available. Hypervitaminosis A is usually treated by stopping intake of the offending food(s), supplement(s), or medication. Most people make a full recovery. High intake of provitamin carotenoids (such as beta-carotene) from vegetables and fruits does not cause hypervitaminosis A, as conversion from carotenoids to the active form of vitamin A is regulated by the body to maintain an optimum level of the vitamin. Carotenoids themselves cannot produce toxicity. ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Types of vitamin A * 2.2 Sources of toxicity * 2.3 Types of toxicity * 3 Mechanism * 3.1 Delivery to tissues * 3.1.1 Absorption * 3.1.2 Storage * 3.1.3 Transport * 3.2 Effects * 3.2.1 Increased bone turnover * 3.2.2 Altered fat-soluble vitamin metabolism * 3.2.2.1 Mitochondrial toxicity * 4 Diagnosis * 4.1 Tests * 4.2 Relevance of blood tests * 4.2.1 Retinol concentrations are nonsensitive indicators * 4.2.2 Retinol esters have been used as markers * 5 Prevention * 5.1 Daily tolerable upper level * 6 Treatment * 7 History * 8 Other animals * 8.1 Treatment * 9 See also * 10 References * 11 External links ## Signs and symptoms[edit] Symptoms may include:[1] * Abnormal softening of the skull bone (craniotabes—infants and children) * Blurred vision * Bone pain or swelling * Bulging fontanelle (infants) * Changes in consciousness * Decreased appetite * Dizziness * Double vision (young children) * Drowsiness * Headache * Gastric mucosal calcinosis[2] * Heart valve calcification[3] * Hypercalcemia * Increased intracranial pressure manifesting as cerebral edema, papilledema, and headache[4] (may be referred to as Idiopathic intracranial hypertension) * Irritability * Liver damage[5][6][7][8][9][10][11][12][13] * Nausea * Poor weight gain (infants and children) * Skin and hair changes * Cracking at corners of the mouth * Hair loss * Higher sensitivity to sunlight * Oily skin and hair (seborrhea) * Premature epiphyseal closure[14][15][16][17][18] * Skin peeling, itching * Spontaneous fracture[19][20] * Yellow discoloration of the skin (aurantiasis cutis) * Uremic pruritus[21] * Vision changes * Vomiting ## Causes[edit] Cod liver oil, a potentially toxic source of Vitamin A. Hypervitaminosis A can result from ingestion of too much vitamin A from diet, supplements, or prescription medications. Hypervitaminosis A results from excessive intake of preformed vitamin A. Genetic variations in tolerance to vitamin A intake may occur.[22] Children are particularly sensitive to vitamin A, with daily intakes of 1500 IU/kg body weight reportedly leading to toxicity.[20] ### Types of vitamin A[edit] * It is "largely impossible" for provitamin carotenoids, such as beta-carotene, to cause toxicity, as their conversion to retinol is highly regulated.[20] No vitamin A toxicity has ever been reported from ingestion of excessive amounts.[23] Overconsumption of beta-carotene can only cause carotenosis, a harmless and reversible cosmetic condition in which the skin turns orange. * Preformed vitamin A absorption and storage in the liver occur very efficiently until a pathologic condition develops.[20] When ingested, 70–90% of preformed vitamin A is absorbed and used.[20] ### Sources of toxicity[edit] * Diet – Liver is high in vitamin A. The liver of certain animals, including the polar bear, bearded seal,[24][25] walrus,[26] and moose,[27] are particularly toxic (see Liver_(food)#Toxicity). * Supplements – Dietary supplements can be toxic when taken above recommended dosages. Cod liver oil is particularly high in vitamin A. * Medications – Many drugs are used on a long-term basis in numerous preventive and therapeutic medical applications, which may lead to hypervitaminosis A.[28] ### Types of toxicity[edit] * Acute toxicity occurs over a period of hours or a few days, and is less of a problem than chronic toxicity. * Chronic toxicity results from daily intakes greater than 25,000 IU for 6 years or longer and more than 100,000 IU for 6 months or longer. ## Mechanism[edit] Absorption and storage in the liver of retinol occur very efficiently until a pathologic condition develops.[20] ### Delivery to tissues[edit] #### Absorption[edit] When ingested, 70–90% of preformed vitamin A is absorbed and used.[20] According to a 2003 review, water-miscible, emusified, and solid forms of vitamin A supplements are more toxic than oil-based supplement and liver sources.[29] #### Storage[edit] 80–90% of the total body reserves of preformed vitamin A are in the liver (with 80–90% of this amount being stored in hepatic stellate cells and the remaining 10–20% being stored in hepatocytes). Fat is another significant storage site, while the lungs and kidneys may also be capable of storage.[20] #### Transport[edit] Until recently, it was thought that the sole important retinoid delivery pathway to tissues involved retinol bound to retinol-binding protein (RBP4). More recent findings, however, indicate that retinoids can be delivered to tissues through multiple overlapping delivery pathways, involving chylomicrons, very low density lipoprotein (VLDL) and low density lipoprotein (LDL), retinoic acid bound to albumin, water-soluble β-glucuronides of retinol and retinoic acid, and provitamin A carotenoids.[30] The range of serum retinol concentrations under normal conditions is 1–3 μmol/l. Elevated amounts of retinyl ester (i.e., >10% of total circulating vitamin A) in the fasting state have been used as markers for chronic hypervitaminosis A in humans. Candidate mechanisms for this increase include decreased hepatic uptake of vitamin A and the leaking of esters into the bloodstream from saturated hepatic stellate cells.[20] ### Effects[edit] Effects include increased bone turnover and altered metabolism of fat-soluble vitamins. More research is needed to fully elucidate the effects. #### Increased bone turnover[edit] Retinoic acid suppresses osteoblast activity and stimulates osteoclast formation in vitro,[23] resulting in increased bone resorption and decreased bone formation. It is likely to exert this effect by binding to specific nuclear receptors (members of the retinoic acid receptor or retinoid X receptor nuclear transcription family) which are found in every cell (including osteoblasts and osteoclasts). This change in bone turnover is likely to be the reason for numerous effects seen in hypervitaminosis A, such as hypercalcemia and numerous bone changes such as bone loss that potentially leads to osteoporosis, spontaneous bone fractures, altered skeletal development in children, skeletal pain, radiographic changes,[20][23] and bone lesions.[31] #### Altered fat-soluble vitamin metabolism[edit] Preformed vitamin A is fat-soluble and high levels have been reported to affect metabolism of the other fat-soluble vitamins D,[23] E, and K. The toxic effects of preformed vitamin A might be related to altered vitamin D metabolism, concurrent ingestion of substantial amounts of vitamin D, or binding of vitamin A to receptor heterodimers. Antagonistic and synergistic interactions between these two vitamins have been reported, as they relate to skeletal health. Stimulation of bone resorption by vitamin A has been reported to be independent of its effects on vitamin D.[23] ##### Mitochondrial toxicity[edit] Preformed vitamin A and retinoids exerts several toxic effects regarding redox environment and mitochondrial function [32] ## Diagnosis[edit] ### Tests[edit] Tests may include:[1] * bone X-rays * blood calcium test * cholesterol test * liver function test * blood test for vitamin A ### Relevance of blood tests[edit] #### Retinol concentrations are nonsensitive indicators[edit] Assessing vitamin A status in persons with subtoxicity or toxicity is complicated because serum retinol concentrations are not sensitive indicators in this range of liver vitamin A reserves.[20] The range of serum retinol concentrations under normal conditions is 1–3 μmol/l and, because of homeostatic regulation, that range varies little with widely disparate vitamin A intakes.[20] #### Retinol esters have been used as markers[edit] Retinyl esters can be distinguished from retinol in serum and other tissues and quantified with the use of methods such as high-performance liquid chromatography.[20] Elevated amounts of retinyl ester (i.e., >10% of total circulating vitamin A) in the fasting state have been used as markers for chronic hypervitaminosis A in humans and monkeys.[20] This increased retinyl ester may be due to decreased hepatic uptake of vitamin A and the leaking of esters into the bloodstream from saturated hepatic stellate cells.[20] ## Prevention[edit] Hypervitaminosis A can be prevented by not ingesting more than the US Institute of Medicine Daily Tolerable Upper Level of intake for Vitamin A. This level is for synthetic and natural retinol ester forms of vitamin A. Carotene forms from dietary sources are not toxic. The dose over and above the RDA is among the narrowest of the vitamins and minerals. Possible pregnancy, liver disease, high alcohol consumption, and smoking are indications for close monitoring and limitation of vitamin A administration. ### Daily tolerable upper level[edit] Life stage group category Upper Level (μg/day) Infants 0–6 months 7–12 months 600 600 Children 1–3 years 4–8 years 600 900 Males 9–13 years 14–18 years 19 – >70 years 1700 2800 3000 Females 9–13 years 14–18 years 19 – >70 years 1700 2800 3000 Pregnancy <19 years 19 – >50 years 2800 3000 Lactation <19 years 19 – >50 years 2800 3000 See the USDA Nutrient Database for the amount of Vitamin A http://ndb.nal.usda.gov/ ## Treatment[edit] * Stopping high vitamin A intake is the standard treatment. Most people fully recover.[1] * Phosphatidylcholine (in the form of PPC or DLPC), the substrate for Lecithin retinol acyltransferase, which converts retinol into Retinyl esters (the storage forms of vitamin A). * Vitamin E may alleviate hypervitaminosis A.[33] * Liver transplantation may be a valid option if no improvement occurs.[34] If liver damage has progressed into fibrosis, synthesizing capacity is compromised and supplementation can replenish PC. However, recovery is dependent on removing the causative agent: halting high Vitamin A intake.[35][36][37][38] ## History[edit] Vitamin A toxicity is known to be an ancient phenomenon; fossilized skeletal remains of early humans suggest bone abnormalities may have been caused by hypervitaminosis A.[20] Vitamin A toxicity has long been known to the Inuit and has been known by Europeans since at least 1597 when Gerrit de Veer wrote in his diary that, while taking refuge in the winter in Nova Zemlya, he and his men became severely ill after eating polar bear liver.[39] In 1913, Antarctic explorers Douglas Mawson and Xavier Mertz were both poisoned (and Mertz died) from eating the livers of their sled dogs during the Far Eastern Party.[40] Another study suggests, however, that exhaustion and diet change are more likely to have caused the tragedy.[41] ## Other animals[edit] Some Arctic animals demonstrate no signs of hypervitaminosis A despite having 10–20 times the level of vitamin A in their livers as other Arctic animals. These animals are top predators and include the polar bear, Arctic fox, bearded seal, and glaucous gull. This ability to efficiently store higher amounts of vitamin A may have contributed to their survival in the extreme environment of the Arctic.[42] ### Treatment[edit] These treatments have been used to help treat or manage toxicity in animals. Although not considered part of standard treatment, they might be of some benefit to humans. * Vitamin E appears to be an effective treatment in rabbits, and[43] prevents side effects in chicks[44] * Taurine significantly reduces toxic effects in rats.[45] Retinoids can be conjugated by taurine and other substances. Significant amounts of retinotaurine are excreted in the bile,[46] and this retinol conjugate is thought to be an excretory form, as it has little biological activity.[47] * Red yeast rice ("cholestin") – significantly reduces toxic effects in rats.[48] * Vitamin K prevents hypoprothrombinemia in rats and can sometimes control the increase in plasma/cell ratios of vitamin A.[49] ## See also[edit] * Vitamin poisoning * Far Eastern Party * Retinoic acid syndrome * Piblokto ## References[edit] 1. ^ a b c https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001390/[full citation needed] 2. ^ Gorospe M, Fadare O (May 2007). "Gastric mucosal calcinosis: clinicopathologic considerations" (PDF). Advances in Anatomic Pathology. 14 (3): 224–8. doi:10.1097/PAP.0b013e31805048ea. PMID 17452819. 3. ^ Huk DJ, Hammond HL, Kegechika H, Lincoln J (February 2013). "Increased dietary intake of vitamin A promotes aortic valve calcification in vivo". 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"Biliary metabolites of all-trans-retinoic acid in the rat". Archives of Biochemistry and Biophysics. 224 (1): 13–8. doi:10.1016/0003-9861(83)90185-6. PMID 6870249. 47. ^ Skare KL, Sietsema WK, DeLuca HF (August 1982). "The biological activity of retinotaurine". The Journal of Nutrition. 112 (8): 1626–30. doi:10.1093/jn/112.8.1626. PMID 7097369. 48. ^ Yeh YH, Lee YT, Hsieh YL (May 2012). "Effect of cholestin on toxicity of vitamin A in rats". Food Chemistry. 132 (1): 311–8. doi:10.1016/j.foodchem.2011.10.082. PMID 26434295. 49. ^ Walker SE, Eylenburg E, Moore T (1947). "The action of vitamin K in hypervitaminosis A". The Biochemical Journal. 41 (4): 575–80. PMC 1258540. PMID 16748217. ## External links[edit] Classification D * ICD-10: E67.0 * ICD-9-CM: 278.2 * MeSH: D006986 * DiseasesDB: 13888 External resources * MedlinePlus: 000350 * eMedicine: med/2382 * Facts about Vitamin A and Carotenoids, from the National Institutes of Health's Office of Dietary Supplements. * v * t * e * Poisoning * Toxicity * Overdose History of poison Inorganic Metals Toxic metals * Beryllium * Cadmium * Lead * Mercury * Nickel * Silver * Thallium * Tin Dietary minerals * Chromium * Cobalt * Copper * Iron * Manganese * Zinc Metalloids * Arsenic Nonmetals * Sulfuric acid * Selenium * Chlorine * Fluoride Organic Phosphorus * Pesticides * Aluminium phosphide * Organophosphates Nitrogen * Cyanide * Nicotine * Nitrogen dioxide poisoning CHO * alcohol * Ethanol * Ethylene glycol * Methanol * Carbon monoxide * Oxygen * Toluene Pharmaceutical Drug overdoses Nervous * Anticholinesterase * Aspirin * Barbiturates * Benzodiazepines * Cocaine * Lithium * Opioids * Paracetamol * Tricyclic antidepressants Cardiovascular * Digoxin * Dipyridamole Vitamin poisoning * Vitamin A * Vitamin D * Vitamin E * Megavitamin-B6 syndrome Biological1 Fish / seafood * Ciguatera * Haff disease * Ichthyoallyeinotoxism * Scombroid * Shellfish poisoning * Amnesic * Diarrhetic * Neurotoxic * Paralytic Other vertebrates * amphibian venom * Batrachotoxin * Bombesin * Bufotenin * Physalaemin * birds / quail * Coturnism * snake venom * Alpha-Bungarotoxin * Ancrod * Batroxobin Arthropods * Arthropod bites and stings * bee sting / bee venom * Apamin * Melittin * scorpion venom * Charybdotoxin * spider venom * Latrotoxin / Latrodectism * Loxoscelism * tick paralysis Plants / fungi * Cinchonism * Ergotism * Lathyrism * Locoism * Mushrooms * Strychnine 1 including venoms, toxins, foodborne illnesses. * Category * Commons * WikiProject [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Hypervitaminosis A	c0020579	29,812	wikipedia	https://en.wikipedia.org/wiki/Hypervitaminosis_A	2021-01-18T19:00:14	{"mesh": ["D006986"], "umls": ["C0020579"], "wikidata": ["Q3100515"]}
Cat bite A cat wounded from the bite of another cat SpecialtyEmergency medicine, plastic surgery, pediatrics, veterinary medicine Cat bites are bites inflicted upon humans, other cats, and other animals by the domestic cat.[1][2] (Latin: Felis catus). Data from the United States show that cat bites represent between 5-15% of all animal bites inflicted to humans,[3][4] but it has been argued that this figure could be the consequence of under-reporting as bites made by Felis catus are considered by some to be unimportant.[5][6] Though uncommon, cat bites can sometimes lead to complications and, very rarely, death.[7][8] ## Contents * 1 Signs and symptoms * 2 Infections * 3 Diagnosis * 4 Prevention * 5 Treatment * 6 Epidemiology * 7 See also * 8 References * 9 External links ## Signs and symptoms[edit] Cat bites are usually considered minor injuries but can result in serious infection.[9] Common symptoms include pain and swelling around the affected area.[3] Sometimes, direct tissue damage from the cat bite can impair mobility or cause tenosynovitis or arthritis.[10] In these cases, surgical consultation is needed to assess severity.[3][4] Some unusual complications, like deep-vein thrombosis,[5] subcutaneous emphysema[11] and fetal tachycardia[11] have been described. Some of the infections acquired from a cat bite can be acquired otherwise, like plague.[12] ## Infections[edit] Ancylostoma braziliense mouthparts Further information: Feline zoonosis The resident flora in the mouth of the domestic cat includes Pasteurella, Staph, Bartonella, and Streptococcus species.[9] Bites from cats develop infections more frequently than bites from dogs.[6] The teeth of a cat are sharp, pointed and can cause deep wounds. After a cat bite, the skin usually closes rapidly over the bite and may trap microorganisms.[13][8] The bite from a cat can infect a person with: * Cat-scratch disease, caused by the bacterium Bartonella henselae[8][14] * Cat-scratch disease is a bacterial disease that people may get after being bitten or scratched by a cat. About 40% of cats carry the bacteria at some time in their mouths, although kittens younger than one year of age are more likely to have it.[15] Most cats with this infection show no signs of illness. * Hookworm, Ancylostoma tubaeforme, Ancylostoma braziliense, and Uncinaria stenocephala * Capnocytophaga canimorsus[16] * Pasteurellosis caused by the bacterial genus Pasteurella[17][18] * Pasteurellosis is a bacterial disease associated with animal bites and scratches. Pasteurella spp is a normal bacterium that also lives in the mouths of healthy cats. The bacteria do not typically make cats sick; however, cats can develop abscesses or skin infections in places where they were scratched or bitten by another animal. In people, pasteurellosis causes painful wound and skin infections. In severe cases, it can cause widespread infection and might even affect the nervous system. * Rabies, a fatal neurologic disease in animals and people, is caused by a virus. Animals and people are most commonly infected through bites from rabid animals. Infected cats may have a variety of signs, but most often have sudden behavioral changes and progressive paralysis.[19] ## Diagnosis[edit] The diagnosis is aided by obtaining a history of the circumstances surrounding the bite. The time the bite was experienced, the location of the bite, and examination of the bite is noted. The person may have drainage from the site of the bite. They may also be febrile, and swelling around the wound may occur. Because the wound from the bite may heal too quickly over the punctures, it may need to be opened and explored. Hydrogen peroxide may be used at home to reopen the wound, with pressure being applied around the wound to drain any abscesses. For deep wounds, this process may need to be repeated. At a hospital, you may request that the site be anesthetized prior to exploration. Neurovascular status is assessed. Immune status may determine treatment as does the presence of transplanted tissue or organs, rheumatic disease, diabetes, HIV/AIDS and sickle cell disease. Swollen lymph nodes and red streaks radiating upward may be evident.[20][14][9] The diagnosis of a cat with rabies is usually evident by observing the cat. Cats with rabies may also appear restless, pant, and attack other animals, people, or objects. Animals with rabies typically die within a few days of appearing sick. Vaccination of the cat can prevent rabies being transmitted by the cat through a bite. If the cat is suspected of being infected with rabies, the person bitten will immediately begin treatment with rabies vaccine.[19] ## Prevention[edit] Cat bites can often be prevented by: * avoiding cats * instructing children not to tease cats or other pets[21] * being cautious with unfamiliar cats * approaching cats with care, even if they appear to be friendly * avoiding rough play with cats and kittens. Rough play is perceived as aggressive. This will lead to the cat being defensive when approached by people. Preventing cat bites includes not provoking the cat. If a cat is reactive, handle it with care, being careful not to trigger any fear or aggression responses. The cat may bite its handler or someone nearby in an effort to defend itself. In the case of dogs, the potential for attack is well known. Unfortunately not in cats, although there are countless documented[22] [23] cases. ## Treatment[edit] The first step in treatment includes washing and then irrigating the bite wound with water and isopropyl alcohol.[24][25][9] Often, a tetanus shot is prescribed.[8] If a cat that has bitten another cat or animal and appears to be ill, the cat would benefit from an assessment and possible treatment by a veterinarian. If the wound has a low risk of being infected, it is sometimes only sutured.[24] A person who has been bitten by a cat with rabies will need specialized treatment. Resulting infections from cat bites can be prevented by immediately washing wounds with soap and warm water. Seek medical attention if the cat has not been vaccinated against rabies.[21] If a cat has bitten someone, and there is no evidence that the cat has been vaccinated against rabies, the person will be treated for rabies infection.[19] ## Epidemiology[edit] The examples and perspective in this article may not represent a worldwide view of the subject. You may improve this article, discuss the issue on the talk page, or create a new article, as appropriate. (December 2017) (Learn how and when to remove this template message) Over 400,000 cat bites are reported each year in the US, though the actual number of bites is much higher since many such bites are under-reported.[20] 40 million households in the United States have domestic cats.[26] Data on the number of people bitten or scratched by cats is limited because most of these incidents are not reported; however, 20%–80% of cat bites and scratches become infected.[17] Cat-scratch disease or cat-scratch fever, an infection that causes fever and swollen lymph nodes, can develop from cat scratches even if they only break the surface of the skin. Based on reports of people treated for cat bites at hospitals, women are most likely to be victims of cat bites and scratches.[19] Because of their smaller build, children are more likely to be bitten on their head, neck and face. Adults are more likely to bitten on the hands and arms.[9] Those who are immunocompromised are more susceptible to infection from a cat bite.[8] Data show that cat bites are more common found in women than in men,[3] and in older adults, particularly those over 75 years old.[3] Cat bites are more frequent in the mornings,[3] during spring and summer.[6] The most commonly affected human body part are the arms.[3] Attackers are usually stray females.[6] ## See also[edit] * Dog bite ## References[edit] 1. ^ Wozencraft, W.C. (2005). "Species Felis catus". In Wilson, D.E.; Reeder, D.M (eds.). Mammal Species of the World: A Taxonomic and Geographic Reference (3rd ed.). Johns Hopkins University Press. pp. 534–535. ISBN 978-0-8018-8221-0. OCLC 62265494. 2. ^ "ITIS Standard Report Page: Felis catus". ITIS Online Database. Reston, Virginia: Integrated Taxonomic Information System. 2011. Retrieved 14 December 2011. 3. ^ a b c d e f g Aziz, Hassan; Rhee, Peter; Pandit, Viraj; Tang, Andrew; Gries, Lynn; Joseph, Bellal (2015-03-01). "The current concepts in management of animal (dog, cat, snake, scorpion) and human bite wounds". Journal of Trauma and Acute Care Surgery. 78 (3): 641–648. doi:10.1097/TA.0000000000000531. ISSN 2163-0755. PMID 25710440. 4. ^ a b Olcott, Jessica L.; Bula-Rudas, Fernando J. (2018-10-01). "Human and Animal Bites". Pediatrics in Review. 39 (10): 490–500. doi:10.1542/pir.2017-0212. ISSN 0191-9601. PMID 30275032. 5. ^ a b Guadarrama-Conzuelo, F; Gutierrez-Castillo, A (2019-06-17). "Cathrombosis: Deep Vein Thrombosis After a Cat Bite - A Case Report". Cureus. 11 (6): e4924. doi:10.7759/cureus.4924. PMC 6692098. PMID 31423400. 6. ^ a b c d Philipsen, T. E. J.; Molderez, C.; Gys, T. (2006-01-01). "Cat And Dog Bites. What To Do?". Acta Chirurgica Belgica. 106 (6): 692–695. doi:10.1080/00015458.2006.11679983. ISSN 0001-5458. PMID 17290697. 7. ^ Gurry, Greta A.; Campion, Veronique; Premawardena, Chamath; Woolley, Ian; Shortt, Jake; Bowden, Donald K.; Kaplan, Zane; Dendle, Claire (2017). "High rates of potentially infectious exposures between immunocompromised patients and their companion animals: an unmet need for education". Internal Medicine Journal. 47 (3): 333–335. doi:10.1111/imj.13361. ISSN 1444-0903. PMID 28260250. 8. ^ a b c d e "First Aid: Animal Bites". The Nemours Foundation. 2017. Retrieved 2017-06-18. 9. ^ a b c d e Maniscalco, K; Edens, MA (April 20, 2017). "Animal Bites". National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved June 17, 2017. 10. ^ Jorup, Christina; Wretlind, Bengt; Settergren, Bo; Sandstedt, Karin; Ekblom, Anna Gerber; Cars, Björn; Farra, Anna; Westling, Katarina (2006-12-01). "Cat bite wound infections: A prospective clinical and microbiological study at three emergency wards in Stockholm, Sweden". Journal of Infection. 53 (6): 403–407. doi:10.1016/j.jinf.2006.01.001. ISSN 0163-4453. PMID 16483663. 11. ^ a b Wagner, Brian K.; Martone, Jeffrey D.; Conte, Harry; Hill, Melissa; Kusan, Karuna (September 2006). "Complications of a Cat Bite". Journal of the American Podiatric Medical Association. 96 (5): 455–457. doi:10.7547/0960455. ISSN 8750-7315. PMID 16988179. 12. ^ Gage, K. L.; Dennis, D. T.; Orloski, K. A.; Ettestad, P.; Brown, T. L.; Reynolds, P. J.; Pape, W. J.; Fritz, C. L.; Carter, L. G.; Stein, J. D. (2000). "Cases of Cat-Associated Human Plague in the Western US, 1977-1998". Clinical Infectious Diseases. 30 (6): 893–900. doi:10.1086/313804. ISSN 1058-4838. PMID 10852811. 13. ^ "Animal Bites". Handcare.org. American Society for Surgery of the Hand. 2017. Archived from the original on 28 July 2017. Retrieved 18 June 2017. 14. ^ a b "Cat scratch disease". U.S. National Library of Medicine. September 10, 2015. Retrieved June 17, 2017. 15. ^ Rijks, J. M.; Cito, F.; Cunningham, A. A.; Rantsios, A.T.; Giovannini, A. (2016). "Disease Risk Assessments Involving Companion Animals: an Overview for 15 Selected Pathogens Taking a European Perspective". Journal of Comparative Pathology. 155 (1): S75–S97. doi:10.1016/j.jcpa.2015.08.003. ISSN 0021-9975. PMID 26422413. 16. ^ Joanna Zajkowska, Monika Król, Daniel Falkowski, Norina Syed, Anna Kamieńska. "Capnocytophaga canimorsus – An Underestimated Danger After Dog or Cat Bite – Review of the Literature", Przegl Epidemiol. 2016;70(2):289-295. n.d. 17. ^ a b Lloret, Albert; Egberink, Herman; Addie, Diane; Belák, Sándor; Boucraut-Baralon, Corine; Frymus, Tadeusz; Gruffydd-Jones, Tim; Hartmann, Katrin; Hosie, Margaret J; Lutz, Hans; Marsilio, Fulvio; Möstl, Karin; Pennisi, Maria Grazia; Radford, Alan D; Thiry, Etienne; Truyen, Uwe; Horzinek, Marian C (2013). "Pasteurella Multocida Infection in Cats". Journal of Feline Medicine and Surgery. 15 (7): 570–572. doi:10.1177/1098612X13489215. ISSN 1098-612X. PMID 23813817. 18. ^ Chomel, Bruno (2014). "Emerging and Re-Emerging Zoonoses of Dogs and Cats". Animals. 4 (3): 434–445. doi:10.3390/ani4030434. ISSN 2076-2615. PMC 4494318. PMID 26480316. 19. ^ a b c d https://www.cdc.gov/healthypets/pets/cats.html This article incorporates public domain material from websites or documents of the Centers for Disease Control and Prevention. 20. ^ a b "Prevent Bite Wounds". American Academy of Pediatrics. 2017. Retrieved June 17, 2017. 21. ^ a b "First Aid: Animal Bites (for Parents) - KidsHealth". 22. ^ "German cat attack: Animal Bites (for Parents) - KidsHealth". 23. ^ "Woman dies after bite: Animal Bites (for Parents) - KidsHealth". 24. ^ a b "Animal bites Fact sheet N°373". World Health Organization. February 2013. Retrieved June 17, 2017. 25. ^ https://www.cdc.gov/healthypets/pets/cats.html#what-to-do This article incorporates public domain material from websites or documents of the Centers for Disease Control and Prevention. 26. ^ https://www.cdc.gov/rabies/pets/index.html This article incorporates public domain material from websites or documents of the Centers for Disease Control and Prevention. ## External links[edit] Classification D * ICD-10: W55.01XA External resources * MedlinePlus: 000888 * v * t * e Animal bites and stings Arthropod bites and stings Arachnid * Demodex mite bite * Scorpion sting * Spider bite / Arachnidism * Latrodectism * Loxoscelism Insects * Ant sting * Bee sting * Cimicosis * Mosquito bite * Pulicosis * Reduviid bite Myriapoda * Centipede bite * Millipede burn Vertebrate * Alligator attack * Bear attack * Beaver attack * Boar attack * Cougar attack * Cat bite * Coyote attack * Crocodile attack * Dingo attack * Dog attack * Killer whale attack * Leopard attack * Lion attack * Monkey bite * Piranha fish attack * Shark attack * Snakebite * Stingray attack * Stonefish attack * Tiger attack * Venomous fish * Walrus attack * Wolf attack Other * Animal attacks * Bristleworm sting * Cephalopod attack * Cone snail sting * Coral dermatitis * Dog bite prevention * Hydroid dermatitis * Jellyfish dermatitis / Jellyfish sting * Leech bite * Man-eater * Portuguese man-of-war dermatitis * Sea anemone dermatitis * Sea urchin injury * Seabather's eruption [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Cat bite	c0417713	29,813	wikipedia	https://en.wikipedia.org/wiki/Cat_bite	2021-01-18T18:31:15	{"wikidata": ["Q30325669"]}
## Summary ### Clinical characteristics. Virtually all individuals with Woodhouse-Sakati syndrome (WSS) have the endocrine findings of hypogonadism (evident at puberty) and progressive childhood-onset hair thinning that often progresses to alopecia totalis in adulthood. More than half of individuals have the neurologic findings of progressive extrapyramidal movements (dystonic spasms with dystonic posturing with dysarthria and dysphagia), moderate bilateral post-lingual sensorineural hearing loss, and mild intellectual disability. To date 32 families (including 23 with a molecularly confirmed diagnosis) with a total of 76 affected individuals have been reported. ### Diagnosis/testing. The diagnosis is established in a proband with suggestive clinical findings and by identification of biallelic pathogenic variants in DCAF17 (formerly known as C2orf37) on molecular genetic testing. ### Management. Treatment of manifestations: Treatment is symptomatic and should be managed by a multidisciplinary team. Hypogonadism requires hormone replacement therapy to induce secondary sex characteristics and promote bone health at the usual age of puberty. Alopecia is treated symptomatically for cosmetic reasons only. Treatment for dystonia is routine; oral medications are tried first and followed in some instances by botulinum toxin injection and/or deep-brain stimulation. Dysarthria often benefits from consultation with a speech therapist. Those with dysphagia often require measures to reduce oral secretions, use of thickened liquids and pureed foods to avoid aspiration, and eventually a gastrostomy to help maintain caloric intake. Hearing loss, intellectual disability, diabetes mellitus, and hypothyroidism are treated as per routine. Surveillance: Monitoring for endocrine abnormalities is recommended at the following ages: hypogonadism (12-14 years), diabetes mellitus (in the 20s or later), hypothyroidism (in the 20s or later). Neurologic manifestations should be monitored by a neurologist as well as experts in rehabilitative medicine, speech, and swallowing. Hearing should be monitored annually. Agents/circumstances to avoid: Persons with dystonia should avoid situations in which the risk of falling is increased. Evaluation of relatives at risk: Molecular genetic testing for the DCAF17 pathogenic variants identified in the proband is appropriate for evaluation of apparently asymptomatic older and younger sibs to identify, as early as possible, those who would benefit from early identification and treatment of potential complications. ### Genetic counseling. WSS is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the pathogenic DCAF17 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 options. ## Diagnosis ### Suggestive Findings Woodhouse-Sakati syndrome (WSS) should be suspected in individuals with the following findings. Endocrine * Hypogonadism (100% of individuals), hypogonadotropic in males and hypergonadotropic in females * Primary amenorrhea in females * Lack of development of secondary sexual characteristics in males and females * Low insulin-like growth factor 1 (IGF-1) (100%) * Adolescent- to young adult-onset diabetes mellitus (66%) * Hypothyroidism (30%) Alopecia. Hair loss beginning in childhood or adolescence, resulting in partial to complete loss of scalp hair and eyelashes (100%) (Figure 1A, 1H) #### Figure 1. Affected individuals from different families with WSS who have variable degrees of alopecia or hair loss and neurologic involvement A. Male age 23 with flat occiput; temporal and frontal alopecia Neurologic * Adolescent to young adult onset of extrapyramidal findings (56%) including focal (later generalized) dystonia and chorea, dysarthria, and dysphagia * Sensorineural hearing loss (SNHL) with onset in childhood (62%) * Intellectual disability (58%) #### Supportive Findings * On MRI: * Variable abnormalities in periventricular white matter (Figure 2A, 2C, 2D) [Al-Semari & Bohlega 2007, Schneider & Bhatia 2008] * Rarely, iron deposition in the globus pallidus (Figure 2B, 2D) [Al-Semari & Bohlega 2007, Gregory & Hayflick 2011, Hdiji et al 2016] * Parental consanguinity #### Figure 2. Brain MRI of individuals with WSS. Arrows indicate the following findings: A. Long TR sequence, showing increased signal intensities in the subcortical regions of the centrum semi-oval ### Establishing the Diagnosis The diagnosis of Woodhouse-Sakati syndrome is established in a proband with suggestive clinical findings and biallelic pathogenic variants in DCAF17 (formerly known as C2orf37) on molecular genetic testing (see Table 1). Molecular testing approaches can include single-gene testing, use of a multigene panel, and more comprehensive genomic testing. * Single-gene testing. Sequence analysis of DCAF17 identifies biallelic pathogenic variants in all individuals with typical findings of WSS. DCAF17 exon and whole-gene deletion/duplication variants have not been reported. However, gene-targeted deletion/duplication analysis may be useful to confirm homozygosity of a pathogenic variant detected by sequence analysis when parental DNA is not available (see Molecular Genetics, Pathogenic variants). For affected individuals who are ethnically Saudi Arabian or Qatari, targeted analysis for pathogenic variants may be performed first: to date, all affected individuals in these populations have been homozygous for the same founder pathogenic variant (c.436delC) [Alazami et al 2008, Ben-Omran et al 2011]. * A multigene panel that includes DCAF17 and other genes of interest (see Differential Diagnosis) may also be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. * More comprehensive genomic testing (when available) including exome sequencing, mitochondrial sequencing, and genome sequencing may be considered if serial single-gene testing (and/or use of a multigene panel that includes DCAF17) fails to confirm a diagnosis in an individual with features of WSS. Such testing may provide or suggest a diagnosis not previously considered (e.g., mutation of a different gene or genes that results in a similar clinical presentation). For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. ### Table 1. Molecular Genetic Testing Used in Woodhouse-Sakati Syndrome View in own window Gene 1MethodProportion of Probands with Pathogenic Variants 2 Detectable by Method DCAF17Sequence analysis 332/32 families Gene-targeted deletion/duplication analysis 4None reported 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on allelic variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include 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 Woodhouse-Sakati syndrome (WSS) is characterized by the endocrine findings of hypogonadism, diabetes mellitus, and hypothyroidism; and progressive childhood-onset alopecia along with neurologic findings of progressive extrapyramidal movements, sensorineural hearing loss, and intellectual disability. WSS was first described in a few consanguineous Saudi families [Woodhouse & Sakati 1983]. Of note, a review of earlier literature revealed two families that appeared to have similar clinical manifestations – one from Lebanon [Slti & Salem 1979] and one from Italy [Bjornstad 1965, Crandall et al 1973]. As of July 2016, 32 families (including 23 families with a molecularly confirmed diagnosis) with a total of 76 affected individuals have been reported. While the majority are from the Middle East (i.e., Saudi Arabia, United Arab Emirates, Qatar, Kuwait, Palestine, Turkey), families from India, Belgium, the Roma population in France, Croatia, Pakistan, Tunisia, and Italy have been reported [Al-Awadi et al 1985, Mégarbané et al 2003, Medica et al 2007, Tatar et al 2009, Steindl et al 2010, Nanda et al 2014, Abdulla et al 2015, Hdiji et al 2016, and references cited below in this section]. #### Endocrine Hypogonadism, present in all affected individuals, manifests as delayed puberty with lack of secondary sexual characteristics. The nature of hypogonadism has been difficult to characterize as both hypergonadotropic and hypogonadotropic hypogonadism have been described [Agopiantz et al 2014]; in about 30% of affected individuals the hormonal profile does not neatly fit either group. Sense of smell is normal. Women typically have primary amenorrhea. Detailed endocrine investigation, available in 52 of the women described in the literature, typically revealed severely reduced or absent estradiol and high FSH and LH, consistent with hypergonadotropic hypogonadism. There appears to be decreased hypothalamic-pituitary responsiveness, as the FSH and LH are not as high as expected for the degree of ovarian failure [Woodhouse & Sakati 1983, Rachmiel et al 2011, Agopiantz et al 2014]. The ovaries are streak or underdeveloped [Al-Swailem et al 2006] and not visualized by laparotomy, laparoscopy, or autopsy [Gül et al 2000, Al-Semari & Bohlega 2007, Ben-Omran et al 2011, Rachmiel et al 2011]. Ovarian biopsy showed fibrous tissue with no identifiable oocysts [Woodhouse & Sakati 1983]. Men have moderately low testosterone and – in contrast to women – inappropriately low gonadotropins, consistent with hypogonadotropic hypogonadism which may be of central or central and peripheral etiology. Semen analysis may show azoospermia [Agopiantz et al 2014, Ali et al 2016]. One male had cryptorchidism [Rachmiel et al 2011]. Although the testes are of normal size, testicular biopsy reveals reduced spermatogenesis with predominance of Sertoli cells and few Leydig cells [Woodhouse & Sakati 1983]. Low insulin-like growth factor 1 (IGF-1). First described in 12 families [Al-Semari & Bohlega 2007], low IGF-1 was identified in all subsequently reported cases [Alazami et al 2010, Ben-Omran et al 2011, Habib et al 2011, Rachmiel et al 2011, Agopiantz et al 2014, Ali et al 2016]. Reduction of IGF1 is more pronounced in females [Al-Semari & Bohlega 2007, Ben-Omran et al 2011]. The low IGF-1 levels may reflect the low sex steroids resulting from hypogonadism. The growth pattern is normal and growth hormone levels are usually normal; short stature is not a part of this syndrome [Agopiantz et al 2014]. Diabetes mellitus. Type 2 diabetes (either insulin dependent or non-insulin dependent) was reported in 66% of all individuals and 96% of those older than age 25 years [Al-Semari & Bohlega 2007, Agopiantz et al 2014]. Hypothyroidism of peripheral origin (primary but without evidence of autoimmunity) was found in 30% of individuals, typically around age 20 years [Al-Semari & Bohlega 2007]. Other. No abnormalities of the corticotropic axis or prolactin [Al-Semari & Bohlega 2007, Agopiantz et al 2014] have been reported. #### Ectodermal Alopecia. All affected individuals have predominantly frontotemporal alopecia with sparse thin scalp hair. Hair loss begins in childhood and often progresses to alopecia totalis in the third or fourth decade or earlier. Eyelashes and eyebrows are absent or sparse. In men, facial hair is absent or underdeveloped. Scanning electron microscopy of the hair shows longitudinal grooves with no specific abnormalities [Devriendt et al 1996, Al-Semari & Bohlega 2007]. Facial skin is often wrinkled in advanced stages conferring a progeroid appearance [Woodhouse & Sakati 1983, Al-Semari & Bohlega 2007, Schneider & Bhatia 2008, Agopiantz et al 2014]. Anodontia. Total loss of teeth is rare; when it occurs, it is usually seen at later stage of the disease [Al-Semari & Bohlega 2007, Steindl et al 2010, Agopiantz et al 2014]. Nails appear to be normal. #### Neurologic Extrapyramidal abnormal movement was seen in more than 56% of reported individuals. In particular, dystonic spasms with dystonic posturing was seen in the majority, including segmental dystonia affecting the craniocervical region, oromandibular region, or one extremity. Often, the first neurologic manifestation is abnormal posturing movements that typically start insidiously in childhood or the early teens. Dysarthria (often with a high-pitched voice) and dysphagia are common. In a majority of individuals, dystonia becomes generalized and disabling (Figure 1B, 1F, 1H). Progressive dystonia of the trunk may lead to severe dystonic scoliosis. As the dystonia progresses, gait difficulties ultimately lead to immobility. Inter- and intrafamilial variability is common [Al-Semari & Bohlega 2007, Schneider & Bhatia 2008, Ben-Omran et al 2011, Ali et al 2016]. For example, families with the founder DCAF17 (c.436delC) pathogenic variant can have dystonia [Al-Semari & Bohlega 2007] or not [Alazami et al 2008]. Of note, although extrapyramidal features were not mentioned in the original report of Woodhouse and Sakati [1983], subsequent follow up in the originally reported families revealed progressive dystonia in a few family members (Figure 1H) [Al-Semari & Bohlega 2007]. Sensorineural hearing loss (SNHL). Moderate bilateral SNHL was noted in 62% of reports. When present, deafness is invariably postlingual, usually starting in adolescence [Woodhouse & Sakati 1983, Al-Semari & Bohlega 2007, Schneider & Bhatia 2008, Ben-Omran et al 2011]. Intellectual disability is described in 58% of individuals. It is typically mild and usually overshadowed by accompanying severe and disabling dystonia, dysarthria, and SNHL. The authors observed ten individuals who were able to complete their college education and hold permanent manual occupations [Author, personal observation]. Other. Seizures with onset in early childhood, tremors, and mild Parkinsonism features were rarely reported [Al-Semari & Bohlega 2007, Schneider & Bhatia 2008]. Polyneuropathy with stocking glove sensory loss and diminished deep tendon reflexes but normal strength has been reported [Schneider & Bhatia 2008]. #### Other Findings Dysmorphic facial features include a long triangular face, prominent nasal bridge, widely spaced eyes, and sparse eyebrows, creating a characteristic facial appearance (Figure 1D, 1E, 1G). Bilateral keratoconus was reported in four individuals [Al-Swailem et al 2006, Schneider & Bhatia 2008, Ben-Omran et al 2011]. Electrocardiographic (ECG) abnormalities (lengthening of the ST segments and T-wave flattening) were described in the original report [Woodhouse & Sakati 1983]; however, they were rarely reported subsequently [Koshy et al 2008, Schneider & Bhatia 2008]. Of note, these ECG abnormalities were asymptomatic and individuals with WSS have no major cardiac manifestations. ### Genotype-Phenotype Correlations There is no clear genotype-phenotype correlation. Even individuals with the same Saudi Arabian founder DCAF17 pathogenic variant (c.436delC) have displayed marked phenotypic variability. ### Prevalence From the time of the original description in 1983 to the present (July 2016), 32 families with 76 affected individuals have been reported. Of these, 44 individuals from 23 families have had the diagnosis confirmed molecularly (see Clinical Description). The carrier frequency of the Saudi Arabian founder variant is 0.00243309 [Abouelhoda et al 2016]. ## Differential Diagnosis ### Table 2. Disorders/Phenotypes to Consider in the Differential Diagnosis of Woodhouse-Sakati Syndrome View in own window Disorder / PhenotypeGene(s)MOIDistinguishing Clinical Features Gonadotropin-releasing hormone deficiencySee footnote 1.XL AD ARIdiopathic hypogonadotropic hypogonadism w/congenital olfactory deficit w/ataxia, epilepsy & congenital paresis of cranial nerves III, IV, VI Gordon Holmes syndrome (OMIM 212840)RNF216 PNPLA6 2ARHypogonadism, cerebellar ataxia, white matter lesions; no alopecia Alopecia, neuropathy, endocrinopathy (ANE) syndrome (OMIM 612079) 3RBM28ARHypogonadotropic hypogonadism, alopecia, adrenal insufficiency and cognitive impairment Hutchinson-Gilford progeria syndromeLMNAAD 4Alopecia, aged-looking skin, joint abnormalities, loss of subcutaneous fat Cockayne syndromeERCC6 ERCC8ARShort stature & appearance of premature aging Deafness-dystonia-optic neuronopathy syndrome (Mohr-Tranebjaerg syndrome)TIMM8A 5XLEarly-onset hearing loss; movement disorder; impaired vision; behavior problems (almost exclusively in males) Neurodegeneration with brain iron storage disordersPANK2 PLA2G6 C19orf12 FA2H ATP13A2 WDR45 COASY FTL CPAR XL AD 6Variable phenotype: variable age of onset, dystonia w/postural instability Brain iron accumulation on MRI DystoniaSee footnote 7.AD AR XLVariable phenotype; hypogonadism & alopecia not observed Deafness and hereditary hearing lossSee footnote 8.AD AR XL mtDNAVariable phenotype w/variable age of onset; hypogonadism not a feature Perrault syndrome (PRLTS)HSD17B4 HARS2 CLPP LARS2 TWNKARHeterogeneous & variable; early deafness, premature ovarian failure, weakness, spasticity AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance; mtDNA = mitochondrial DNA; XL = X-linked 1\. See Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency for associated genes. 2\. See PNPLA6-Related Disorders. 3\. Only one family reported to date as per OMIM 4\. Almost all individuals with Hutchinson-Gilford progeria syndrome have the disorder as the result of a de novo autosomal dominant pathogenic variant. 5\. Deafness-dystonia-optic neuronopathy syndrome occurs as either a single-gene disorder resulting from mutation of TIMM8A or a contiguous gene deletion syndrome at Xq22. 6\. Eight of the ten genetically defined types of neurodegeneration with brain iron accumulation are inherited in an autosomal recessive manner. Exceptions are: beta-propeller protein-associated neurodegeneration, caused by de novo pathogenic variants in WDR45, which is inherited in an X-linked manner with suspected male lethality; and neuroferritinopathy, caused by pathogenic variants in FTL, which is inherited in an autosomal dominant manner. 7\. See Dystonia Overview for associated genes. 8\. See Deafness and Hereditary Hearing Loss Overview for associated genes. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with Woodhouse-Sakati syndrome (WSS), the following evaluations are recommended: * Endocrine. Evaluation for possible endocrine findings (if not done at the time of diagnosis) relating to: hypogonadism, low IGF-1, diabetes mellitus, hypothyroidism * Ectodermal. Assessment of scalp hair * Neurologic * Neurologic examination for evidence of dystonia (if not done at the time of diagnosis) (see Dystonia Overview) * Speech and language assessment of dysarthria and dysphagia * Assessment of hearing (see Hereditary Hearing Loss and Deafness) * Assessment of psychomotor development (in young children) or intellectual ability in individuals older than age six years * Other. Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations No specific treatment exists for WSS. All treatment is symptomatic. #### Endocrine * Hypogonadism. Sex hormone replacement therapy at the usual age of puberty to induce and maintain secondary sex characteristics and promote bone health Note: Standard replacement hormonal treatment will not promote fertility. It may be possible to stimulate testes with gonadotropins and harvest sperm with assisted reproductive technology. * Low IGF-1. Treatment with recombinant IGF-1 not recommended: no evidence shows that it improves the clinical features of WSS [Agopiantz et al 2014]. Of note, IGF-1 levels may increase with sex hormone replacement therapy. * Diabetes mellitus. Standard treatment * Hypothyroidism. L-thyroxine replacement therapy #### Ectodermal Treatment is symptomatic and cosmetic only. #### Neurologic Movement disorders * Dystonia. Treatment is aimed at relieving symptoms [Albanese et al 2015]: * Oral medications are usually tried first: * Anticholinergics such as trihexyphenidyl (moderately effective for ~40%-50% of individuals) Trihexyphenidyl can be titrated to high doses (~100 mg/day) in younger individuals. Anticholinergic side effects, particularly cognitive effects, must be monitored closely. * Baclofen (Lioresal®) * Benzodiazepines, especially clonazepam * Other medications tried alone or in combination with the above categories: levodopa, carbamazepine, and dopamine depleting agents (reserpine, tetrabenazine) * Botulinum toxin injections directly into dystonic muscles are generally the treatment of choice for adult-onset focal dystonias. For individuals with more widespread dystonia in whom specific muscle groups produce disabling symptoms, such injections may also be helpful, and are often used in combination with oral medications. * If medications fail, surgery to enable deep-brain stimulation (DBS) of the globus pallidus interna (GPi) has been shown to be an effective treatment for some forms of medically refractory primary generalized dystonia [Vidailhet et al 2007, Crowell & Shah 2016]. Its use in WSS has not been documented. * Dysarthria. Consultation with a speech therapist may be helpful. * Dysphagia. Oral secretions in individuals with bulbar symptoms can be reduced with tricylic antidepressants and anticholinergic agents, thus reducing the need for suctioning. Swallowing difficulties can be alleviated by thickening liquids and pureeing solid food, as well as eventually using a gastrostomy tube to help maintain caloric intake and hydration. Nutritional management by a knowledgeable nutritionist is helpful. Sensorineural hearing loss. See Hereditary Hearing Loss and Deafness. ### Surveillance Monitor for endocrine abnormalities: * Hypogonadism at age 12-14 years * Diabetes mellitus in the teens and later * Hypothyroidism in the teens and later Neurologic manifestations should be monitored by experts in rehabilitative medicine, speech, and swallowing. Dystonia may require monitoring by a neurologist. Monitor hearing annually. ### Agents/Circumstances to Avoid Persons with dystonia should avoid situations in which the risk of falling is increased. ### Evaluation of Relatives at Risk Molecular genetic testing for known familial DCAF17 pathogenic variants is appropriate for the evaluation of apparently asymptomatic older and younger sibs of a proband in order to identify as early as possible those who will benefit from early identification and treatment of potential complications. 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	Woodhouse-Sakati Syndrome	c0342286	29,814	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK378974/	2021-01-18T20:49:25	{"mesh": ["C536742"], "synonyms": ["Hypogonadism", "Alopecia", "Diabetes Mellitus", "Intellectual Disability", "and Extrapyramidal Syndrome"]}
Lipoblastoma Lipoblastoma. Note the plexiform vascular pattern and small immature adipocytes. SpecialtyOncology Lipoblastoma is a type of subcutaneous benign fatty tumor.[1][2] Types include: * Benign lipoblastomatosis, a tumor, also known as an embryonic lipoma, which usually occurs in children under three years old. This is the tumor of brown fat cells. * Myxoid lipoblastoma, a cutaneous condition characterized by excess mucin ## See also[edit] * Lipoblast * Lipoma ## References[edit] 1. ^ A. M. A. de Schepper; Paul M. Parizel; Filip M. Vanhoenacker (2006). Imaging of soft tissue tumors. Springer. pp. 233–6. ISBN 978-3-540-24809-5. OCLC 181443089. 2. ^ Akbar Bonakdar-Pour; William R. Reinus; Jasvir S. Khurana (22 September 2009). Diagnostic Imaging of Musculoskeletal Diseases: A Systematic Approach. Springer. p. 319. ISBN 978-1-58829-947-5. Retrieved 11 March 2011. * 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 This Dermal and subcutaneous growths 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	Lipoblastoma	c1260965	29,815	wikipedia	https://en.wikipedia.org/wiki/Lipoblastoma	2021-01-18T18:50:12	{"gard": ["12015"], "mesh": ["D062689"], "umls": ["C1260965"], "orphanet": ["247762"], "wikidata": ["Q1827370"]}
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: "Computer-induced medical problems" – news · newspapers · books · scholar · JSTOR (November 2010) (Learn how and when to remove this template message) This article possibly contains original research. Please improve it by verifying the claims made and adding inline citations. Statements consisting only of original research should be removed. (July 2013) (Learn how and when to remove this template message) (Learn how and when to remove this template message) Computer-induced health problems can be an umbrella term for the various problems a computer user can develop from extended and incorrect computer use. A computer user may experience many physical health problems from using computers extensively over a prolonged period of time in an inefficient manner. The computer user may have poor etiquette when using peripherals, for example incorrect posture. Reportedly, excessive use of electronic screen media can have ill effects on mental health related to mood, cognition, and behavior, even to the point of hallucination.[1] ## Contents * 1 Overview * 2 Common computer-induced medical problems * 2.1 Carpal Tunnel Syndrome * 2.2 Computer Vision Syndrome * 2.3 Musculoskeletal problems * 2.4 Mental problems * 3 Treatment * 4 See also * 5 References ## Overview[edit] In today’s world using computers is a necessity for the majority of people but not many people actually consider the medical consequences that working with computers can cause, such as damaged eyesight, bad posture, arthritis in fingers and computer stress injuries that can be caused by sitting in one position for a prolonged period of time. The above problems are more commonly associated with old age but due to many factors such as poor component design, proximity of the user to the screen and an excess of consecutive working hours mean that the above problems can feature in both young and old computer users. This is an extremely important issue as computers become more important in every corner of employment the medical effects caused by them will elevate unless sufficient research is performed and time is dedicated into eliminating and reducing these problems as much as possible. It is estimated that today at least 75% of all jobs involve some level of computer use; this means three-quarters of the workforce are being exposed to numerous health problems, the same can be said of students and educators who do not go through any day without access to a computer for academic work. The figure for people working with and using computers recreationally is to increase considerably in the coming years so it is crucially important that these problems are identified and resolved sooner rather than later in an effort to reduce if not eradicate these problems. ## Common computer-induced medical problems[edit] Notable physical medical problems that can arise from using computers include Carpal Tunnel Syndrome, Computer Vision Syndrome, and Musculoskeletal problems.[2] ### Carpal Tunnel Syndrome[edit] The medical problem associated with computer-related work is carpal tunnel syndrome (CTS). CTS is a stress-related injury caused by repetitive movement of joints, especially the wrist, and can lead to numerous musculoskeletal problems. It has become very common among Computer professionals due to poorly placed computer components and extensive typing over a long period of time. Studies conducted show that one in eight computer professionals suffer from CTS.[3] This study was conducted over 21 companies and the majority of sufferers said that they experienced acute and in some cases severe pain due to CTS. The main cause of CTS seems to be debatable, however, with many sources saying that the syndrome is predominantly caused by the acute positioning of the wrist while typing and this problem is exacerbated by the need for the user to be crouching towards the screen while typing. Different research conducted cites the mouse as being the main cause of CTS[3] as it was found that among the fingers the right thumb was revealed to be more susceptible to CTS due to the acute position of the thumb while using the mouse. CTS, although prevalent, seems to be very difficult to ameliorate or cure due to the consistency in the design of computer components such as the mouse and the keyboard, but some companies are leading the way with technologies such as touch screen monitors which will reduce stress on the hand and wrist. Employers in major companies are also taking measures to ameliorate CTS by implementing frequent work breaks and work rotation procedures to ensure that employees aren’t working on a single computer for hours on end "a higher level of intensity of computer work results in higher risk for CTS."[4] which causes severe stress on the joints and thus can lead to CTS Cumulative trauma disorders are caused by "people who sit at PC workstations or visual display terminals in fast-paced, repetitive keystroke jobs. Their fingers, wrists, arms, necks, and back may become so weak and painful that they cannot work,"[5] Many people do not think about this when they look at their computer while using it. It is important to note that everything down to the keyboard has a design process behind it focusing on user interface.[6] ### Computer Vision Syndrome[edit] In many cases, frequent computer users suffer from computer vision syndrome, which is a degenerative eye problem which can result in severely reduced eyesight (Myopia), blurred vision, overall eye tiredness and even Glaucoma. Computer Eye Syndrome is an umbrella term for many problems but the causes of these problems can be easily identified. When using a computer due to the size and setup of the monitor and components it is necessary for the user to be within at least two feet of the monitor when performing any type of computational work. This presents many problems especially in older monitors due to an elevated amount of monitor glare, poor display quality and insufficient picture display refresh rates. Although these problems are more evident in older computers the newer models are not free from these problems either. Studies have been conducted.[7] They state “Treatment requires a multidirectional approach combining ocular therapy with adjustment of the workstation”[7] which shows these problems are quite easily solved with minimal investment from computer manufacturers through producing higher quality monitors with better resolution and refresh rates. The most common form of Computer Vision Syndrome is a condition termed Dry Eye, which results in itchy, sore and even the illusion that something is stuck in your eye. This condition is often caused by extensively long period looking at a computer screen. Video screens have a design process for user interface. Video screens can cause eyestrain from prolonged viewing. Cathode ray tubes are what are used to display the information on your computer. These send off radiation. This is a concern that has been taken into account when designing better computer screens for user interface.[5][6] ### Musculoskeletal problems[edit] Another medical issue caused by the use of computers is back and posture problems. These problems relate to musculoskeletal disorders caused by the need for the user to be crouched and hunched towards the monitors and computer components due to the design and positioning of these particular computer peripherals. This hunching forward of the user causes posture and back problems but is also the cause of severe and acute pain in the upper back, particularly pain in the neck and or shoulders. A study [8] was conducted where 2146 technical assistants installed a computer program to monitor the musculoskeletal pain they suffered and answered questionnaires on the location and severity of the pain. The study showed interesting results, as it detailed how in the majority of cases any pain suffered was aggravated and exacerbated by the use of computer peripherals like the mouse and keyboard but overall the pain did not originate from using computers. "Moreover, there seems to be no relationship between computer use and prolonged and chronic neck and shoulder pain"[8] This is a positive study for computer manufacturers but although the pain may not originate from computer peripherals there is no doubt that the pain is exacerbated by their use and this revelation alone should lead computer manufacturers to pioneer new technologies that reduce the risk of posture or musculoskeletal problems aggravated by the use of poorly designed and linearly designed computer peripherals. In another study,[9] It was found that women are at a greater risk than men to suffer from musculoskeletal problems than men. Two explanations given were that "women appear to consistently report more neck and upper extremity symptoms than men.", and that women may assume more taxing positions while working than men do due to differences in anthropometrics. ### Mental problems[edit] Public Health England said children who spend too long on the internet face social problems such as loneliness, depression and anxiety.[10] According to Dr. Victoria Dunckley, excessive use of electronic screen media can have ill effects on mental health related to mood, cognition, and behavior—and may even result in psychosis in the form of hallucination.[1] She calls this "Electronic Screen Syndrome" (ESS). She claims the root of these symptoms appears to be linked to repeated stress on the nervous system, making self-regulation and stress management less efficient. She says interacting with screens shifts the nervous system into fight-or-flight mode which leads to dysregulation as an inability to modulate one’s mood, attention, or level of arousal in a manner appropriate to one’s environment. ## Treatment[edit] Modern medical treatment for computer-induced medical problems like carpal tunnel syndrome include splints, surgery, corticosteroids, and physiotherapy therapy.[11] Alternative medicine for computer-induced medical problems has also been shown to be effective, notably acupuncture.[12] ## See also[edit] * Computer vision syndrome * Keratoconjunctivitis sicca * Musculoskeletal disorder * Glaucoma ## References[edit] 1. ^ a b "Electronic Screen Syndrome: An Unrecognized Disorder? Screentime and the rise of mental disorders in children". Jul 23, 2012. 2. ^ "Computer-related injuries". 3. ^ a b Andersen, J. H.; Thomsen, JF; Overgaard, E; Lassen, CF; Brandt, LP; Vilstrup, I; Kryger, AI; Mikkelsen, S (2003). "Computer Use and Carpal Tunnel Syndrome: A 1-Year Follow-up Study". JAMA. 289 (22): 2963–9. doi:10.1001/jama.289.22.2963. PMID 12799404. 4. ^ Ali, KM; Sathiyasekaran, BW (2006). "Computer professionals and Carpal Tunnel Syndrome (CTS)". International Journal of Occupational Safety and Ergonomics. 12 (3): 319–25. CiteSeerX 10.1.1.1002.3294. doi:10.1080/10803548.2006.11076691. PMID 16984790. 5. ^ a b O’Brien & Marakas, 2007, p. 553 6. ^ a b O’Brien, J. & Marakas, G. (2011).Management Information System, 10e. New York, NY. McGraw-Hill Irwin.[page needed] 7. ^ a b Blehm, Clayton; Vishnu, Seema; Khattak, Ashbala; Mitra, Shrabanee; Yee, Richard W. (2005). "Computer Vision Syndrome: A Review". Survey of Ophthalmology. 50 (3): 253–62. doi:10.1016/j.survophthal.2005.02.008. PMID 15850814. 8. ^ a b Andersen, J H; Harhoff, M; Grimstrup, S; Vilstrup, I; Lassen, C F; Brandt, L P A; Kryger, A I; Overgaard, E; et al. (2008). "Computer mouse use predicts acute pain but not prolonged or chronic pain in the neck and shoulder" (PDF). Occupational and Environmental Medicine. 65 (2): 126–31. doi:10.1136/oem.2007.033506. PMID 17681996. 9. ^ Wahlstro¨m, Jens. "Ergonomics, musculoskeletal disorders and computer work" (PDF). oxfordjournals.org. Oxford University Press. Retrieved 20 April 2014. 10. ^ "Too much time on web 'gives children mental health problems'". 11. ^ Feuerstein, Michael; Burrell, Lolita M.; Miller, Virginia I.; Lincoln, Andrew; Huang, Grant D.; Berger, Ruth (1999). "Clinical management of carpal tunnel syndrome: A 12-year review of outcomes". American Journal of Industrial Medicine. 35 (3): 232–45. doi:10.1002/(SICI)1097-0274(199903)35:3<232::AID-AJIM3>3.0.CO;2-G. PMID 9987556. 12. ^ Khosrawi, Saeid; Moghtaderi, Alireza; Haghighat, Shila (2012). "Acupuncture in treatment of carpal tunnel syndrome: A randomized controlled trial study". Journal of Research in Medical Sciences. 17 (1): 1–7. PMC 3523426. PMID 23248650. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Computer-induced medical problems	None	29,816	wikipedia	https://en.wikipedia.org/wiki/Computer-induced_medical_problems	2021-01-18T18:34:35	{"wikidata": ["Q5157396"]}
Scheie syndrome Other namesMPS I-S Structure of dermatan sulfate, one of the molecules that accumulates in the lysosomes of Hurler syndrome patients SymptomsSymptoms are variable, but may include: mild learning disabilities, psychiatric issues, visual problems, skeletal deformities, carpal tunnel syndrome, aortic valve disease, and/or sleep apnea Usual onsetSymptoms may appear by age 5; diagnosis is usually made after age 10 CausesDeficiency of the alpha-L iduronidase enzyme Differential diagnosisOther forms of MPS I; Hunter Syndrome; other mucopolysaccharidoses TreatmentEnzyme replacement therapy with iduronidase; surgery may be necessary PrognosisThese patients may live to adulthood. Frequency1 in 500,0000[1] Scheie syndrome is a disease caused by a deficiency in the enzyme iduronidase, leading to the buildup of glycosaminoglycans (GAGs) in the body. It is the most mild subtype of mucopolysaccharidosis type I; the most severe subtype of this disease is called Hurler Syndrome. Scheie syndrome is characterized by corneal clouding, facial dysmorphism, and normal lifespan.[2][3] People with this condition may have aortic regurgitation.[4] ## Contents * 1 Symptoms * 2 Genetics * 3 History * 4 See also * 5 References * 6 External links ## Symptoms[edit] The symptoms of Scheie syndrome are variable, but are milder than Hurler Syndrome. Symptoms may begin to appear by age 5, but affected children are often not diagnosed until after age 10. Patients with Scheie Syndrome may have normal intelligence, or they may have mild learning impairments or psychiatric problems. Glaucoma, retinal degeneration, and clouded corneas may cause visual impairments. Aortic valve disease may be present, along with carpal tunnel syndrome, deformed hands and feet, stiff joints, or sleep apnea. People with Scheie syndrome may live into adulthood.[1] ## Genetics[edit] Scheie syndrome has an autosomal recessive pattern of inheritance. Children with Scheie Syndrome carry two defective copies of the IDUA gene, which has been mapped to the 4p16.3 site on chromosome 4. This is the gene which encodes for the protein iduronidase. All patients with subtypes of MPS I have mutations in the same gene, leading to deficiencies of the same enzyme. However, patients with Scheie Syndrome have a greater level of iduronidase activity than patients with Hurler Syndrome. Because Scheie syndrome is an autosomal recessive disorder, affected persons have two nonworking copies of the gene. A person born with one normal copy and one defective copy is called a carrier. They will produce less α-L-iduronidase than an individual with two normal copies of the gene. The reduced production of the enzyme in carriers, however, remains sufficient for normal function; the person should not show any symptoms of the disease. ## History[edit] In 1919, Gertrud Hurler, a German pediatrician, described a syndrome involving corneal clouding, skeletal abnormalities, and mental retardation. This became known as Hurler Syndrome.[5][6] In 1962, a milder variant of Hurler Syndrome was identified by Scheie, leading to the designation of Scheie syndrome.[7] ## See also[edit] * Hunter syndrome (MPS II) * Sanfilippo syndrome (MPS III) * Morquio syndrome (MPS IV) ## References[edit] 1. ^ a b "Mucopolysaccharidoses Fact Sheet". National Institute of Neurological Disorders and Stroke. 15 Nov 2017. Retrieved 11 May 2018. 2. ^ Ropper AH, Samuels MA, "Chapter 37. Inherited Metabolic Diseases of the Nervous System" (Chapter). Ropper AH, Samuels MA: Adams and Victor's Principles of Neurology, 9e: http://www.accessmedicine.com/content.aspx?aID=3636356. 3. ^ Bonakdar-Pour, Akbar (2010-06-09). Diagnostic Imaging of Musculoskeletal Diseases: A Systematic Approach. ISBN 9781597453554. 4. ^ "Scheie syndrome - National Library of Medicine - PubMed Health". ncbi.nlm.nih.gov. Retrieved 19 January 2014. 5. ^ Hurler's syndrome at Who Named It? 6. ^ Hurler, G. (1919). "Über einen Typ multipler Abartungen, vorwiegend am Skelettsystem". Zeitschrift für Kinderheilkunde. 24 (5–6): 220–234. doi:10.1007/BF02222956. S2CID 34471544. 7. ^ Moore, David; Connock, Martin J.; Wraith, Ed; Lavery, Christine (2008-01-01). "The prevalence of and survival in Mucopolysaccharidosis I: Hurler, Hurler-Scheie and Scheie syndromes in the UK". Orphanet Journal of Rare Diseases. 3: 24. doi:10.1186/1750-1172-3-24. ISSN 1750-1172. PMC 2553763. PMID 18796143. ## External links[edit] Classification D * ICD-10: E76.0 * OMIM: 607016 External resources * Orphanet: 93474 * v * t * e Lysosomal storage diseases: Inborn errors of carbohydrate metabolism (Mucopolysaccharidoses) Catabolism * MPS I * Hurler Syndrome, Hurler-Scheie Syndrome, Scheie Syndrome * MPS II: Hunter Syndrome * MPS III: Sanfilippo Syndrome * MPS IV: Morquio Syndrome * MPS VI: Maroteaux-Lamy Syndrome * MPS VII: Sly Syndrome * MPS IX: Hyaluronidase deficiency [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Scheie syndrome	c0026708	29,817	wikipedia	https://en.wikipedia.org/wiki/Scheie_syndrome	2021-01-18T18:57:25	{"gard": ["12561"], "mesh": ["D008059"], "omim": ["607016"], "orphanet": ["93474"], "synonyms": ["MPS1S", "MPSIS", "Mucopolysaccharidosis type 1S", "Mucopolysaccharidosis type IS"], "wikidata": ["Q3281299"]}
A rare, genetic, non-syndromic, obesity disease characterized by severe, early-onset obesity, associated with major hyperphagia and endocrine abnormalities, resulting from leptin receptor deficiency. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Obesity due to leptin receptor gene deficiency	c3554225	29,818	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=179494	2021-01-23T18:28:22	{"omim": ["614963"], "icd-10": ["E66.8"]}
Cleidocranial dysplasia is a condition that primarily affects development of the bones and teeth. Signs and symptoms of cleidocranial dysplasia can vary widely in severity, even within the same family. Individuals with cleidocranial dysplasia usually have underdeveloped or absent collarbones, also called clavicles ("cleido-" in the condition name refers to these bones). As a result, their shoulders are narrow and sloping, can be brought unusually close together in front of the body, and in some cases can be made to meet in the middle of the body. Delayed maturation of the skull (cranium) is also characteristic of this condition, including delayed closing of the growth lines where the bones of the skull meet (sutures) and larger than normal spaces (fontanelles) between the skull bones that are noticeable as "soft spots" on the heads of infants. The fontanelles normally close in early childhood, but they may remain open throughout life in people with this disorder. Some individuals with cleidocranial dysplasia have extra pieces of bone called Wormian bones within the sutures. Affected individuals are often shorter than other members of their family at the same age. Many also have short, tapered fingers and broad thumbs; flat feet; knock knees; short shoulder blades (scapulae); and an abnormal curvature of the spine (scoliosis). Typical facial features include a wide, short skull (brachycephaly); a prominent forehead; wide-set eyes (hypertelorism); a flat nose; and a small upper jaw. Individuals with cleidocranial dysplasia often have decreased bone density (osteopenia) and may develop osteoporosis, a condition that makes bones progressively more brittle and prone to fracture, at a relatively early age. Women with cleidocranial dysplasia have an increased risk of requiring a cesarean section when delivering a baby, due to a narrow pelvis preventing passage of the infant's head. Dental abnormalities are very common in cleidocranial dysplasia and can include delayed loss of the primary (baby) teeth; delayed appearance of the secondary (adult) teeth; unusually shaped, peg-like teeth; misalignment of the teeth and jaws (malocclusion); and extra teeth, sometimes accompanied by cysts in the gums. In addition to skeletal and dental abnormalities, people with cleidocranial dysplasia may have hearing loss and are prone to sinus and ear infections. Some young children with this condition are mildly delayed in the development of motor skills such as crawling and walking, but intelligence is unaffected. ## Frequency Cleidocranial dysplasia occurs in approximately 1 per million individuals worldwide. It is likely underdiagnosed because many affected individuals have mild signs and symptoms. ## Causes Cleidocranial dysplasia is usually caused by mutations in the RUNX2 gene. This gene provides instructions for making a protein that is involved in the development and maintenance of teeth, bones, and cartilage. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone (a process called ossification), except for the cartilage that continues to cover and protect the ends of bones and is present in the nose, airways, and external ears. The RUNX2 protein is a transcription factor, which means it attaches (binds) to specific regions of DNA and helps control the activity of particular genes. Researchers believe that the RUNX2 protein acts as a "master switch," regulating a number of other genes involved in the development of cells that build bones (osteoblasts) and in the development of teeth. The RUNX2 gene mutations that cause cleidocranial dysplasia reduce or eliminate the activity of the protein produced from one copy of the RUNX2 gene in each cell, decreasing the total amount of functional RUNX2 protein. This shortage of functional RUNX2 protein interferes with the normal development of bones, cartilage, and teeth, resulting in the signs and symptoms of cleidocranial dysplasia. In rare cases, individuals with a deletion of genetic material that includes RUNX2 and other nearby genes may experience additional features, such as developmental delay, resulting from the loss of these genes. In about 30 percent of individuals with cleidocranial dysplasia, no mutation in the RUNX2 gene has been found. The cause of the condition in these individuals is unknown. ### Learn more about the gene associated with Cleidocranial dysplasia * RUNX2 ## Inheritance Pattern This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Some affected individuals inherit the mutation from one affected parent. Often the parent is mildly affected, and in some cases had not previously been recognized as having the disorder. Other cases result from new mutations in the gene. These cases 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	Cleidocranial dysplasia	c0008928	29,819	medlineplus	https://medlineplus.gov/genetics/condition/cleidocranial-dysplasia/	2021-01-27T08:25:12	{"gard": ["6118"], "mesh": ["D002973"], "omim": ["119600"], "synonyms": []}
For a general discussion of hereditary prostate cancer, see 176807. Mapping Amundadottir et al. (2006) reported a common variant on 8q24 associated with prostate cancer, discovered in a genomewide linkage scan in 871 Icelandic men with prostate cancer that grouped into 323 extended families. The linkage signal had a maximum lod score of 2.11 (D8S529 at 148.25 cM). To refine the location of the linkage signal, they performed an association study and found the strongest association to prostate cancer for allele -8 of the microsatellite DG8S737, with an odds ratio (OR) of 1.79. Of SNPs identified within the linkage disequilibrium block that contains DG8S737, allele A of rs1447295 showed the strongest association with prostate cancer (OR = 1.72, P = 1.7 x 10(-9)). The result was replicated in 3 case-control series of European ancestry in Sweden and the United States. Combining results from the 3 case-control groups of European ancestry gave an estimated OR of 1.62 (P = 2.7 x 10(-11)) for DG8S737 -8 and an OR of 1.51 (P = 1.0 x 10(-11)) for rs1447295. Amundadottir et al. (2006) found that about 19% of affected men and 13% of the general population carried at least 1 copy of allele -8, yielding a population attributable risk (PAR) of about 8%. The association was also replicated in an African American case-control group with a similar OR, in which 41% of affected individuals and 30% of the population were found to be carriers. This led to a greater estimated PAR (16%) for the African American group, which may contribute to the higher incidence of prostate cancer in African American men than in men of European ancestry. Freedman et al. (2006) performed a whole-genome admixture scan in 1,597 African Americans and identified a 3.8-Mb interval on chromosome 8q24 as significantly associated with susceptibility to prostate cancer (lod = 7.1). The increased risk associated with African ancestry at 8q24 was greater in men diagnosed before 72 years of age (P less than 0.00032), and Freedman et al. (2006) suggested that this finding supports the epidemiologic observation that the higher risk for prostate cancer in African Americans is greater in younger men and attenuates with older age. The authors noted that the same region had been identified by Amundadottir et al. (2006) through linkage analysis of prostate cancer, followed by fine mapping. Freedman et al. (2006) strongly replicated this association (P less than 4.2 x 10(-9)) but found that the previously described alleles (DG8S737, rs1447295) did not explain more than a fraction of the admixture signal. Following up on the study of Amundadottir et al. (2006), which identified the correlated variants allele A rs1447295 and allele -8 of microsatellite marker DG8S737 associated with prostate cancer, Gudmundsson et al. (2007) performed a genomewide association scan of 1,453 affected Icelandic individuals and 3,064 controls using microarray analysis followed by 4 replication studies. The rs1447295 gave the most significant results for association (OR = 1.71, P = 1.6 x 10(-14)). They constructed a 14-SNP haplotype that efficiently tagged a susceptibility variant, rs16901979, relatively uncommon (2 to 4%) in individuals of European descent but very common (approximately 42%) in African Americans. The rs16901979 variant showed a stronger association with affected individuals who had an earlier age at diagnosis. Gudmundsson et al. (2007) estimated the PAR of the rs16901979 A allele alone to be 24% in African Americans and approximately 13% in populations of European ancestry; with updated estimates for the effect of DG8S737 -8 in African Americans, the 2 variants had a combined estimated PAR of 31% in that population. The authors suggested that these 2 variants could account for a large fraction of the excess of prostate cancer rates in African Americans relative to European Americans. The genomic region containing rs16901979 did not contain any known genes or microRNAs. Following up on the admixture scan of Freedman et al. (2006) in African Americans with prostate cancer, Haiman et al. (2007) genotyped 2,973 SNPs in up to 7,518 men with or without prostate cancer from African American, Japanese American, Native Hawaiian, Latino, and European American populations. They identified 7 risk variants, 5 theretofore undescribed, spanning 430 kb and each independently predicting risk for prostate cancer. The strongest association was for rs6983561 (P = 7.9 x 10(-19)). The variants defined common genotypes that span more than a 5-fold range of susceptibility to prostate cancer in some populations. None of the variants aligned to a known gene or altered the protein sequence of an encoded protein. In a genomewide association analysis using 550,000 SNPs in a nested case-control study (1,172 cases and 1,157 controls of European origin), Yeager et al. (2007) identified a new association at 8q24 with an independent effect on prostate cancer susceptibility. The most significant signal, rs6983267, was 70 kb centromeric to the previously reported rs1447295, but showed little evidence of linkage disequilibrium with it. A combined analysis with 4 additional studies (total: 4,296 cases and 4,299 controls) confirmed association with prostate cancer for rs6983267 in the centromeric locus (P = 9.42 x 10(-13); heterozygote OR: 1.26, 95% confidence interval: 1.13-1.41; homozygote OR: 1.58, 95% confidence interval: 1.40-1.78). Each SNP remained significant in a joint analysis after adjusting for the other (rs1447295, P = 1.41 x 10(-11); rs6983267, P = 6.62 x 10(-10)). These observations, combined with compelling evidence for a recombination hotspot between the 2 markers, indicated the presence of at least 2 independent loci within 8q24 that contribute to prostate cancer in men of European ancestry. Yeager et al. (2007) estimated that the PAR of the new locus, marked by rs6983267, is higher than the locus marked by rs1447295 (21% versus 9%). They noted that rs6983267 has an overall population frequency in northern Europeans of 50% for the at-risk G allele. Witte (2007) reviewed the studies of Amundadottir et al. (2006), Freedman et al. (2006), Gudmundsson et al. (2007), Haiman et al. (2007), and Yeager et al. (2007). Combining results for rs1447295, which resides in a region designated 'region 1,' across the studies of Gudmundsson et al. (2007), Haiman et al. (2007), and Yeager et al. (2007) indicated an extraordinarily strong association, with an adjusted P value of 4 x 10(-29). However, Witte (2007) noted that, as in the studies of Amundadottir et al. (2006) and Freedman et al. (2006), relatively weak associations were observed in this region among African Americans. Merging the findings for rs16901979, within region 2 located approximately 350 kb upstream of region 1, gave an adjusted P value of 1 x 10(-19). Combining results for rs6983267, within region 3 between regions 1 and 2, from the 3 later studies gave an adjusted P value of 1 x 10(-11). Witte (2007) concluded that SNPs across all 3 neighboring regions seem to contribute independently to the 8q24 signal, and the combined effects of SNPs across regions closely follow a multiplicative model. In a large genomewide association study to search for common variants with moderate risk, Thomas et al. (2008) confirmed the association of 2 independent SNPs at 8q24 with prostate cancer, 4242382 (P = 1.12 x 10(-4)) and rs6983267 (P = 3.92 x 10(-4)). Eeles et al. (2008) likewise confirmed the association, identifying 20 SNPs on 8q24 with P less than 10(-6). Yeager et al. (2008) used next-generation sequencing technology to conduct a resequence analysis of a 136-kb region on chromosome 8q24 in 39 cases of advanced prostate cancer and 40 controls of European origin. The study yielded a comprehensive catalog of common SNPs within this region, including 442 novel SNPs, as well as the pattern of linkage disequilibrium across the region. Yeager et al. (2008) suggested that their results would be useful in choosing SNPs for fine mapping of association signals in 8q24 in prostate and colorectal cancer and for investigations of the functional consequences of select common variants. Several groups found association of the prostate cancer risk-associated SNP rs6983267 with susceptibility to colorectal cancer; see CRCS2, 611469. Yeager et al. (2009) reported a genomewide association study in 10,286 cases and 9,135 controls of European ancestry in the Cancer Genetic Markers of Susceptibility (CGEMS) initiative. They identified a new association with prostate cancer risk on chromosome 8q24 (rs620861, P = 1.3 x 10(-10), heterozygote OR, 1.17, 95% CI 1.10-1.24; homozygote OR, 1.33, 95% CI 1.21-1.45). The risk is associated with the C allele of this SNP. Because previous studies had identified multiple loci on 8q24 associated with prostate cancer risk, Al Olama et al. (2009) performed a comprehensive analysis of SNP associations across 8q24 by genotyping tag SNPs in 5,504 prostate cancer cases and 5,834 controls. They confirmed associations at 3 previously reported loci and identified additional loci in 2 other linkage disequilibrium blocks (rs1006908: per-allele OR = 0.87, P = 7.9 x 10(-8); rs620861: OR = 0.90, P = 4.8 x 10(-8)). Eight SNPs in 5 linkage disequilibrium blocks were independently associated with prostate cancer susceptibility. The 2 highest were rs6983267 with a per allele OR of 1.26, 95% CI of 1.18-1.35, and P value of 6.2 x 10(-23); and rs10090154, with a per-allele OR of 1.47 and P value of 6.8 x 10(-24). Gudmundsson et al. (2009) reported a prostate cancer genomewide association follow-up study. They identified association with 2 SNPs on chromosome 8q24.21, 16902094G (OR 1.21, P = 6.2 x 10(-15)) and rs445114T (OR = 1.14, P = 4.7 x 10(-10)). In a multivariate analysis using 22 prostate cancer risk variants typed in the Icelandic population, Gudmundsson et al. (2009) estimated that carriers in the top 1.3% of the risk distribution are at 2.5 times greater risk of developing the disease than members of the general population. Tuupanen et al. (2009) and Sotelo et al. (2010) independently determined that rs6983267 lies within a functional TCF4 (TCF7L2; 602228)-binding enhancer element of the MYC gene (190080). Tuupanen et al. (2009) were unable to show a definite correlation between rs6983267 genotype and MYC expression. However, Sotelo et al. (2010) found that the T allele of rs6983267 consistently stimulated activity of a MYC reporter to a greater extent than the G allele in both the presence and absence of beta-catenin (CTNNB1; 116806)/TCF4. The effect of rs6983267 was not large, but it was highly reproducible, with p less than 0.0022. Gudmundsson et al. (2012) analyzed 32.5 million variants discovered by whole-genome sequencing 1,795 Icelanders, and identified a new low-frequency variant at 8q24 associated with prostate cancer in European populations, rs188140481-A (odds ratio = 2.90; p(combined) = 6.2 x 10(-34)), with an average risk allele frequency in controls of 0.54%. This variant is only very weakly correlated (r(2) less than or equal to 0.06) with previously reported risk variants at 8q24, and its association remained significant after adjustment for all risk-associated variants known to that time. Carriers of rs188140481-A were diagnosed with prostate cancer 1.26 years younger than noncarriers (p = 0.0059). Chung et al. (2011) performed resequencing and fine mapping of a region in chromosome 8q24 (region 2) that had been shown to have the strongest association with prostate cancer susceptibility in Japanese Americans and African Americans (e.g., Haiman et al., 2007). They mapped the association peak within a region of approximately 13 kb (chr8:128.16-128.175 Mb, NCBI36) and demonstrated that this region was transcribed, yielding a long noncoding RNA (PRNCR1; 615452) whose expression was upregulated in prostate cancer and its precursor lesions. Chung et al. (2011) identified a 4-SNP haplotype (ATTT) involving rs1456315, SNP34 (chr8:128,173,151, NCBI36), rs5013678, and rs7463708 that showed significant association with prostate cancer in the Japanese population (p = 2.00 x 10(-24), OR = 1.74, 95% confidence interval = 1.56-1.93). They hypothesized that the 8q24 region 2 prostate cancer susceptibility locus is likely to be located within a linkage disequilibrium block encompassing these SNPs (chr8:128,173,119-128,173,237, NCBI36). Breyer et al. (2014) found that 8q24 genomewide association study (GWAS) SNPs are cis-acting expression quantitative trait loci (eQTLs) that modify POU5F1B (615739) expression in normal prostate. In normal prostate tissues, risk alleles for prostate cancer susceptibility by GWAS were consistently accompanied by reduced POU5F1B expression, whereas the protective alleles are accompanied by increased POU5F1B expression. Breyer et al. (2014) found that POU5F1B and POU5F1 (164177) are coexpressed in normal prostate. The risk allele rs6983267 was significantly associated with reduced POU5F1B (p = 0.001) and POU5F1 (p = 0.005) expression in normal prostate of white subjects and was trending for all subjects combined. POU5F1B and POU5F1 were coexpressed in prostate cancer, but POU5F1 expression in prostate cancer accompanied indices of poor prognoses. Breyer et al. (2014) found that the risk allele of rs6983267 marked several common haplotypes encompassing the adjacent gene, POU5F1B. These haplotypes did not have consistent risk effects either within or across the tested populations. In contrast, the protective allele of rs6983267 marked a haplotype that was consistently inversely associated with prostate cancer risk among United States study subjects of European descent, United States study subjects of African descent, and Finnish study subjects. Although this protective haplotype was the most common one in the subjects of European descent (42% frequency in control subjects), it was notably less common among those of African descent (17% frequency in control subjects). Predicted deleterious alleles of 2 POU5F1B missense SNPs, rs6998061 (G176E) and rs7002225 (E238Q), mark that haplotype. In the POU5F1B region, the effect of the GWAS SNP rs6983267 is correlated with the effects of these 2 missense SNPs, the latter more directly detecting risk effects among United States subjects of European descent. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	PROSTATE CANCER, HEREDITARY, 10	c2931456	29,820	omim	https://www.omim.org/entry/611100	2019-09-22T16:03:38	{"doid": ["10283"], "mesh": ["C537243"], "omim": ["611100"], "orphanet": ["1331"]}
A subtype of autosomal recessive limb-girdle muscular dystrophy characterized by a childhood onset of progressive shoulder and pelvic girdle muscle weakness and atrophy frequently associated with calf hypertrophy, diaphragmatic weakness, and/or variable cardiac abnormalities. Mild to moderate elevated serum creatine kinase levels and positive Gowers sign are 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	Gamma-sarcoglycan-related limb-girdle muscular dystrophy R5	c0410173	29,821	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=353	2021-01-23T19:04:03	{"gard": ["2429"], "mesh": ["C535900"], "omim": ["253700"], "umls": ["C0410173"], "icd-10": ["G71.0"], "synonyms": ["Autosomal recessive limb-girdle muscular dystrophy type 2C", "Gamma-sarcoglycan-related LGMD R5", "Gamma-sarcoglycanopathy", "LGMD due to gamma-sarcoglycan deficiency", "LGMD type 2C", "LGMD2C", "Limb-girdle muscular dystrophy due to gamma-sarcoglycan deficiency", "Limb-girdle muscular dystrophy type 2C"]}
A number sign (#) is used with this entry because Kearns-Sayre syndrome is caused by various mitochondrial deletions. Kearns (1965) reported 9 unrelated patients with ophthalmoplegia, pigmentary degeneration of the retina, and cardiomyopathy as leading features. Less consistent features were weakness of facial, pharyngeal, trunk and extremity muscles, deafness, small stature, electroencephalographic changes, and markedly increased cerebrospinal fluid protein. In none of the 9 was a positive family history present. Shy et al. (1967) described a 21-year-old black woman with progressive ptosis, external ophthalmoplegia, retinitis pigmentosa, ataxia, absent deep tendon reflexes, elevated cerebrospinal fluid protein, and histologic features compatible with either Hurler syndrome (MPS I; see 607014) or Refsum disease (266500). Neither phytanic acid nor mucopolysaccharide was found in excess in the tissues, however. Hurwitz et al. (1969) described affected brother and sister. They and both parents had amino aciduria which was of uncertain relationship to the myopathy. Clinically the myopathy most resembled that described by Batten and Turner (see congenital myopathy; 255300). Ophthalmoplegia and floppiness also occur with myotubular myopathy (see centronuclear myopathy; 255200), but this entity was excluded by the muscle biopsy in the cases of Hurwitz et al. (1969). Ross et al. (1969) described the association of chronic progressive external ophthalmoplegia and complete heart block, and noted 4 earlier reports of the same. Rosenberg et al. (1968) reviewed syndromes involving ophthalmoplegia. Iannaccone et al. (1974) observed progressive ophthalmoplegia in females in 4 successive generations and demonstrated ragged-red fibers in skeletal muscle from the extremities. Electron microscopy showed subsarcolemmal clusters of mitochondria containing paracrystalline inclusions. Nonfamilial cases were reported by Olson et al. (1972) and others. The great difficulty in classification of cases of external ophthalmoplegia was noted by many authors. Butler and Gadoth (1976) reported a 17-year-old man and found reports of 19 cases in the literature, all of which were sporadic. Berenberg et al. (1977) reviewed 5 new cases and 30 others from the literature. They suggested that a 'persistent viral infection' may be causal. Drachman (1975) gave a classification of disorders associated with progressive external ophthalmoplegia, which he termed 'ophthalmoplegia plus' (Drachman, 1968). Bastiaensen et al. (1978) described 4 patients who had chronic progressive external ophthalmoplegia with retinal, neurologic, endocrine, and auditory anomalies. Three had signs of cardiomyopathy, with abnormalities confirmed by histologic study of a cardiac biopsy in one. Biochemical studies showed disturbances in pyruvate and lactate metabolism and in respiratory control. Biopsy of skeletal muscle in all 4 showed aggregates of abnormal mitochondria. The pedigrees of 2 families with many affected members in an autosomal dominant pattern, including several instances of male-to-male transmission, were diagrammed. Bertorini et al. (1978) referred to this condition as 'childhood oculocraniosomatic neuromuscular disease with ragged-red fibers.' Mitochondrial abnormalities were present. In some cases Bertorini et al. (1978) demonstrated the presence of a major, diffuse leukoencephalopathy by means of computerized axial tomography. Robertson et al. (1979) reported an 8-year-old girl who had electron-microscopically abnormal mitochondria in skeletal muscle and, by computerized axial tomography, cerebellar and brainstem atrophy and calcification in the region of the basal ganglia. With the possibility of mitochondrial inheritance in mind, Egger and Wilson (1983) studied the pedigrees of 6 affected families whose members they had examined personally and of 24 families described in the literature. In 27 families maternal transmission occurred exclusively; in 3 there was also paternal transmission in 1 generation. Altogether, 51 mothers and only 3 fathers had transmitted the condition, which the authors referred to as mitochondrial cytopathy. They concluded that mitochondrial inheritance is very likely. Fine (1978) outlined the characteristics expected of mitochondrial inheritance, based on the fact that the mitochondria are probably derived exclusively from the mother. The complete nucleotide sequence of the mitochondrial chromosome, which might be called man's 25th chromosome or chromosome M, has been determined (Anderson et al., 1981)--all 16,569 basepairs. Lestienne and Ponsot (1988) described a 5-kb deletion in the mitochondrial DNA from muscle of a patient with Kearns-Sayre syndrome. The deletion was observed only in muscle mitochondria and not in DNA from lymphocytes or fibroblasts. The deletion was mapped to the region including the sequence for 4 subunits of complex I, 2 subunits of complex IV and V, and 5-to-8 tRNA genes. Holt et al. (1988) analyzed 25 patients with mitochondrial myopathy associated with various neurologic symptoms, some of which included the ophthalmoplegia and ptosis characteristic of Kearns-Sayre syndrome. Nine cases were found to harbor heteroplasmic deletions OH and OL. Moraes et al. (1989) surveyed mitochondrial encephalomyopathy patients for mitochondrial DNA deletions. Deletions were found in 78% of Kearns-Sayre patients, 56% of chronic progressive external ophthalmoplegia-plus patients, but none of the patients with MERRF (545000), MELAS (540000), Leigh syndrome, or infantile mitochondrial myopathy (551000). Egger and Wilson (1983) referred to homochondrial and heterochondrial persons; homoplasmic and heteroplasmic were later preferred terms. Ogasahara et al. (1985) described a KSS patient with reduced levels of coenzyme Q(10) in serum and in the mitochondrial fraction of skeletal muscle. The patient had been well until age 12 when progressive ophthalmoparesis and ptosis were first observed. Bilateral atypical degeneration of the retina and hearing loss were noted at age 18. After administration of coenzyme Q(10), 60-120 mg daily for 3 months, serum levels of lactate and pyruvate became normal, with improvement of a previously existing first-degree atrioventricular block and improvement in ocular movements. Bernal et al. (1986) found clear autosomal recessive inheritance of the Kearns-Sayre syndrome in an inbred kindred in Colombia. Whitaker et al. (1987) restudied the pituitary from one of the cases of Kearns and Sayre (1958) and labeled the patient's disorder as Laurence-Moon syndrome. Jankowicz et al. (1977) reported a father and son with pigmentary retinopathy, chronic progressive external ophthalmoplegia (CPEO), myopathy, and ataxia, associated with a cardiac conduction defect in the son, who had mitochondrial abnormalities on muscle biopsy. A similar but variable spectrum of clinical features was observed by Leveille and Newell (1980) in a pedigree that appeared to support autosomal dominant inheritance. In this family, 1 male with CPEO and limb weakness had a daughter with CPEO, retinopathy, cardiac arrhythmias, and proximal myopathy. The father had ragged-red fibers on muscle biopsy but his daughter did not. Scorza Smeraldi et al. (1983) presented a family with 5 affected in 3 generations and transmission only by females. Close linkage to HLA was excluded. Moraes et al. (1989) found deletions in muscle mitochondrial DNA of 32 of 123 patients with various mitochondrial myopathies or encephalopathies. All patients had progressive external ophthalmoplegia. Some patients had only ocular myopathy, whereas others had Kearns-Sayre syndrome. Deletions ranged in size from 1.3 to 7.6 kb, but in 11 patients, an identical 4.9-kb deletion was found in the same location. Zeviani et al. (1988) found large-scale deletions in muscle mitochondrial DNA in all 7 patients with KSS studied. Deletions ranged in size from 2.0 to 7.0 kb and did not localize to any single region of the mitochondrial genome. The proportion of mutated chromosomes in each KSS patient ranged from 45 to 75% of total mtDNA. Channer et al. (1988) reported a 21-year-old man in whom the Kearns-Sayre syndrome was associated with rapid development of progressive congestive cardiac failure requiring cardiac transplantation. Rowland et al. (1988) described concordantly affected monozygotic twins with KSS. Johns et al. (1989) found that in each of 4 patients with chronic progressive external ophthalmoplegia and a large deletion of mitochondrial DNA, the deletion breakpoint occurred within a directly repeated sequence of 13-18 basepairs, present in different regions of the normal mitochondrial genome. In 2 of the patients the deletions were identical. Partially deleted and normal mitochondrial DNAs were found in all tissues examined, but in very different proportions, indicating that these mutations originated before the primary cell layers diverged. Comparison of the repeated sequences showed a consensus of 11 nucleotides, suggesting involvement of a recombinational event in the development of the deletions. Larsson et al. (1990) found heteroplasmy for mtDNA deletions in muscle of 3 patients with KSS. The deletions were mapped to the same region of mtDNA but were of different sizes. Two of the 3 deletions may have included nucleotide 8993 which has been demonstrated to be the site of mutation in NARP syndrome (551500; 516060.0001). The same type of deletion could also be detected in fibroblasts in all 3 cases, but the percentage was considerably lower. In 2 cases, the fraction of mtDNA increased with time in muscle and this increase paralleled the progression of the disease. One case spontaneously recovered from an infantile sideroblastic anemia before the development of KSS. The anemia was of the type seen in Pearson marrow-pancreas syndrome (557000). There have been rather numerous examples of children surviving the pancytopenic crisis of Pearson syndrome and subsequently developing progressive symptoms of KSS (Norby et al., 1994). Poulton et al. (1991) described a patient with Kearns-Sayre syndrome and 2 asymptomatic relatives, the mother and a maternal aunt, all of whom were found to carry the same mtDNA mutation. This was the first report of deletion of mtDNA in the germline. Larsson et al. (1992) described a woman with Kearns-Sayre syndrome and a high percentage of deleted mtDNA in muscle. Although the mtDNA deletion was detected in fibroblasts, bone marrow, and peripheral blood cells by Southern blot analysis, it was detected in all tissues examined when polymerase chain reaction (PCR) was used. The patient had healthy parents and 9 healthy sibs. No deleted mtDNA was detected in the blood of the patient's mother. The patient delivered a healthy daughter in whom no mtDNA deletion was detected by PCR. The presence of deleted mtDNA was excluded at a fractional level of less than 1:100,000 in all examined tissues. Fischel-Ghodsian et al. (1992) pointed out that the same 4,977-bp deletion has been identified in patients with 2 very different diseases: KSS and Pearson marrow-pancreas syndrome. Thus it is not possible to predict the clinical phenotype from the size or location of the deletion; instead, differential tissue distribution of the deletion is probably a critical determinant of phenotype. For example, in KSS the deletion has not been detected by Southern blotting in blood, whereas in Pearson syndrome it is easily detectable. However, Fischel-Ghodsian et al. (1992) described an 11-year-old boy with clinically characteristic KSS and a 7.4-kb mitochondrial DNA deletion between nucleotides 7194 and 14595. Southern blotting demonstrated that 75% of the mitochondrial DNA molecules from peripheral blood had the deletion. Thus, the molecular distinction between KSS and Pearson syndrome was blurred and it was necessary to question whether tissue distribution is a sufficient explanation for the difference in phenotype. In a case of Kearns-Sayre syndrome, Remes et al. (1993) found a deletion in the mitochondrial chromosome comprising 3,236 bp starting from nucleotide 10170. The deletion was bracketed by direct repeats that were unusual in that one of them was located 11-13 nucleotides from the deletion site and both were conserved, which should not occur in slip replication or illegitimate elongation. The deleted region was demarcated on the deletion side by sequences that could be predicted to form hairpin structures. The arrangement around the deletion bore some resemblance to that described by Rotig et al. (1991) in association with Pearson marrow-pancreas syndrome. Identical deletions have been reported in KSS, Pearson syndrome, and CPEO. The tissue distribution of mutant mtDNA is, however, different. In Pearson syndrome, high levels of mutant mtDNA are present in all tissues, particularly blood. In KSS, they are more localized to muscle and the central nervous system. In CPEO, the mutant mtDNA is probably still more localized. It is not known what determines the subsequent clinical course: Pearson syndrome may evolve into KSS and this seems to be associated with a change in the distribution of abnormal mtDNA, which decreases in blood and accumulates in muscle. Poulton et al. (1994) suggested that the mitochondrial chromosome rearrangements that have previously been thought to represent simple deletions have, in fact, a more complex genetic abnormality and that the failure to recognize the complexity results from the use of inappropriate restriction enzymes to linearize mtDNA. The finding of families of rearranged mtDNA molecules in 3 patients with KSS prompted Poulton et al. (1994) to investigate a further 18 patients with KSS/CPEO who had previously documented mtDNA deletions, 1 of whom had a history of Pearson syndrome. They detected mtDNA duplication in 10 of 10 patients with KSS, while deletion monomers were the only recombinant mtDNA easily detectable in 8 of 8 patients with CPEO. Deletion dimers were found only in cases having duplications. Thus, duplications of mtDNA seem to be a hallmark of KSS, including the patient where Pearson syndrome was the first manifestation. Poulton et al. (1994) suggested that duplication of mtDNA is characteristic of early-onset KSS and that the balance of mtDNA rearrangements may be central to the pathogenesis of this unique group of disorders. Replicative segregation of mtDNA can produce large differences in the proportions of wildtype and mutant mtDNAs in different cell types of patients with mitochondrial encephalomyopathy. Shoubridge et al. (1997) noted that these differences are particularly striking in the skeletal muscle of patients with KSS, a sporadic disease associated with large-scale mtDNA deletions, and in sporadic patients with tRNA point mutations. Although the skeletal muscle fibers of these patients invariably contain a large proportion of mutant mtDNAs, mutant mtDNAs are rare or undetectable in satellite cells cultured from the same muscle biopsy specimens. Since satellite cells are responsible for muscle fiber regeneration, restoration of the wildtype mtDNA genotype might be achieved in these patients by encouraging muscle regeneration. To test this concept, Shoubridge et al. (1997) rebiopsied a patient with the KSS phenotype and an mtDNA point mutation in the MTTL2 gene (590055.0001) and analyzed muscle fibers regenerating at the site of the original muscle biopsy. Regenerating fibers were identified by morphologic criteria and by expression of neural cell adhesion molecule (116930). All such fibers were positive for cytochrome c oxidase (COX) activity by cytochemistry and essentially homoplasmic for wildtype mtDNA, while the majority of non-regenerating fibers were COX-negative and contained predominantly mutant mtDNAs. These results demonstrated that it may be possible to improve muscle function in similar patients by methods that promote satellite cell incorporation into existing myofibers. In postmortem examination of 2 patients with KSS, Tanji et al. (1999) found a moderate loss of Purkinje cells and spongiform degeneration of the cerebellar white matter. The dentate nuclei showed spongiform degeneration and capillary proliferation, but no significant loss of neurons. Immunostaining of neurons in the dentate nuclei showed a marked reduction of mitochondrial-encoded proteins. Tanji et al. (1999) concluded that the findings likely underlie the cerebellar dysfunction in KSS. Wang et al. (1999) reproduced the biochemical, morphologic, and physiologic features of the dilated cardiomyopathy of Kearns-Sayre syndrome in the mouse by heart-specific inactivation of mitochondrial DNA gene expression through disruption of the gene encoding mitochondrial transcription factor A (TFAM; 600438). Lertrit et al. (1999) found a 3.5-kb deletion of mtDNA by Southern blot analysis. The deleted position was localized to nucleotides 10208-13765 or nucleotides 10204-13761, spanning the coding area of subunits 3 (ND3; 516002), 4L (ND4L; 516004), 4 (ND4; 516003), and 5 (ND5; 516005). Of the respiratory chain enzyme complex I, as well as the tRNA genes for histidine, serine, leucine, and arginine. The sequence flanking the deletion was a 4-bp repeat of TCCC. All 4 patients, who were not known to be related, had exactly the same 3,558-bp mtDNA deletion. Although they had the same deletion, clinical features were different: 2 had experienced onset during childhood, whereas the other 2 came to the hospital at ages greater than 30 years. The clinical symptoms that presented since childhood, such as hypotonia, epilepsy, and ataxia, involved the neuromuscular system. Both adult patients presented with chronic progressive external ophthalmoplegia, ptosis in both eyes, and pigmentary retinopathy. All 4 patients were heteroplasmic for the deletion. As with several other reported deletions, the defect in this case preserved the promoters of transcription of heavy and light strands, the 12-S and 16-S ribosomal RNA genes, and the origin of heavy strand replication. Thus, the affected mtDNA must be competent for replication to account for the high proportion of genomes with deletions. The deletion was found in heteroplasmic form in muscle samples from the 4 patients but not in their leukocytes. Two patients had KSS and ragged-red fibers on muscle biopsy. Lertrit et al. (1999) reported that the 3.5-kb deletion appears to be unique to Thai patients and that the common 4977-bp deletion (nucleotides 8470-13446) found elsewhere in Asia, in Japanese (Goto et al., 1990; Anan et al., 1995), Taiwanese (Lee et al., 1994), and Chinese, had not been found in Thai patients. Although endocrinopathies (e.g., growth hormone deficiency, hypogonadism, diabetes mellitus, and hypoparathyroidism) are common in KSS, Boles et al. (1998) appeared to have provided the first report of nonautoimmune Addison disease in KSS. The patient had a 4.9-kb deletion extending from approximately 2 o'clock in the ND5 gene to 6 o'clock in the ATP8 gene (516070). Barshop et al. (2000) reported a patient who presented with 2-oxoadipic aciduria and 2-aminoadipic aciduria (204750) at 2 years of age with manifestations typical of organic acidemia, episodes of ketosis and acidosis, progressive to coma. This resolved and the key metabolites disappeared from the urine and blood. At 9 years of age, she developed typical Kearns-Sayre syndrome with complete heart block, retinopathy, and ophthalmoplegia. Southern blot revealed a deletion in the mitochondrial genome. Puoti et al. (2003) reported a mother and son with KSS who both carried an identical large heteroplasmic mtDNA rearrangement detected in muscle and blood lymphocytes. The rearrangement was present in 2 forms: an mtDNA deletion in skeletal muscle, and a combination of partially deleted and partially duplicated mtDNA molecules in blood. Puoti et al. (2003) emphasized that, although rare, mother-to-offspring transmission of large mtDNA rearrangements is possible. Pineda et al. (2006) reported a child with an incomplete form of KSS and a large mtDNA deletion. The patient had a profound decrease of cerebrospinal fluid folate levels with normal serum folate levels, suggesting a transport defect across the blood-brain barrier. Oral folinic acid treatment resulted in marked clinical improvement, particularly with regard to near normalization of white matter lesions. History Poulton et al. (1989) described a duplication of about 8 kb in the mitochondrial genome in several tissues in 2 patients with mitochondrial myopathy and multisystem involvement. Both patients were heteroplasmic. INHERITANCE \- Mitochondrial GROWTH Height \- Short stature HEAD & NECK Head \- Microcephaly Ears \- Sensorineural hearing loss Eyes \- Progressive external ophthalmoplegia \- Pigmentary retinopathy \- Ptosis CARDIOVASCULAR Heart \- Complete heart block \- Cardiomyopathy \- Cardiac conduction defects GENITOURINARY Kidneys \- Renal tubular acidosis \- Fanconi syndrome MUSCLE, SOFT TISSUES \- Muscle weakness \- Ragged-red fibers seen on muscle biopsy NEUROLOGIC Central Nervous System \- Cerebellar ataxia \- Basal ganglia calcifications \- Diffuse signal abnormality of central white matter \- Dementia \- Seizures \- Sensory neuropathy \- Motor neuropathy METABOLIC FEATURES \- Lactic acidosis ENDOCRINE FEATURES \- Diabetes mellitus \- Hypoparathyroidism \- Addison disease HEMATOLOGY \- Sideroblastic anemia LABORATORY ABNORMALITIES \- Increased cerebrospinal fluid (CSF) protein (>100mg/dl) \- Lactic acidosis \- Decreased cerebrospinal fluid folic acid \- Decreased serum and muscle coenzyme Q \- Mitochondrial DNA deletions MISCELLANEOUS \- Onset before age 20 \- Most cases are sporadic \- Single mitochondrial DNA deletions are found in sporadic KSS patients \- Some pedigrees are consistent with autosomal dominant inheritance \- Multiple mitochondrial DNA deletions are found in autosomal dominant pedigrees MOLECULAR BASIS \- Caused by mutation in the mitochondrial tRNA (leucine)-1 gene (MTTL1, 590050.0011 ) \- Caused by deletion of multiple genes in the mitochondrial DNA ▲ 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	KEARNS-SAYRE SYNDROME	c0022541	29,822	omim	https://www.omim.org/entry/530000	2019-09-22T16:16:49	{"doid": ["12934"], "mesh": ["D007625"], "omim": ["530000"], "icd-10": ["H49.81"], "orphanet": ["480"], "synonyms": ["Alternative titles", "OPHTHALMOPLEGIA, PIGMENTARY DEGENERATION OF RETINA, AND CARDIOMYOPATHY", "OCULOCRANIOSOMATIC SYNDROME", "OPHTHALMOPLEGIA-PLUS SYNDROME", "MITOCHONDRIAL CYTOPATHY", "OPHTHALMOPLEGIA, PROGRESSIVE EXTERNAL, WITH RAGGED-RED FIBERS", "CHRONIC PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MYOPATHY", "CPEO WITH MYOPATHY", "CPEO WITH RAGGED-RED FIBERS"], "genereviews": ["NBK1224", "NBK1203"]}
Lethal occipital encephalocele-skeletal dysplasia syndrome is a rare, genetic, bone development disorder characterized by occipital and parietal bone hypoplasia leading to occipital encephalocele, calvarial mineralization defects, craniosynostosis, radiohumeral fusions, oligodactyly and other skeletal anomalies (arachnodactyly, terminal phalangeal aplasia of the thumbs, bilateral absence of the great toes, pronounced bilateral angulation of femora, shortened limbs, advanced osseous maturation). Fetal death in utero is associated. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Lethal occipital encephalocele-skeletal dysplasia syndrome	c3280729	29,823	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=293925	2021-01-23T17:58:03	{"omim": ["614416"], "icd-10": ["Q87.5"]}
repeated occurrence of excessive sweating during sleep This article is about the medical condition. For the television series, see Night Sweats. Night sweats Other namesSleep sweats, nocturnal hyperhidrosis SpecialtyInfectious disease, oncology Night sweats, or also referred to as nocturnal hyperhidrosis (Hyperhidrosis - a medical term for excessive sweating [1] \+ nocturnal - night) is the repeated occurrence of excessive sweating during sleep.[2] The person may or may not also perspire excessively while awake. One of the most common causes of night sweats in women over 40 is the hormonal changes related to menopause and perimenopause.[3] This is a very common occurrence during the menopausal transition years. Over 80% of women experience hot flashes, which may include excessive sweating, during menopause. [4] Night sweats range from being relatively harmless to a sign of underlying disease. Night sweats may happen because the sleep environment is too warm, either because the bedroom is unusually hot or because there are too many covers on the bed.[2] Night sweats have been associated with a long list of clinical conditions.[5] However, there is very little evidence that supports clinical recommendations for this condition.[5] ## Associated conditions[edit] The condition may be a sign of various disease states, including but not exclusive to the following: * Cancers * Lymphoma[6][7] * Leukemia[6][7] * Infections * HIV/AIDS[6][8] * Tuberculosis[6][7] * Mycobacterium avium-intracellulare infection[6] * Infectious mononucleosis[6] * Fungal infections (histoplasmosis, coccidioidomycosis)[6] * Lung abscess[6] * Infective endocarditis[6] * Brucellosis[9] * Pneumocystis pneumonia (most often - in immunocompromised individuals) * Endocrine disorders * Menopause[10] * Premature ovarian failure[6] * Hyperthyroidism[6] * Diabetes mellitus (nocturnal hypoglycemia)[6] * Endocrine tumors (pheochromocytoma, carcinoid)[6] * Orchiectomy[6] * Rheumatic disorders * Takayasu's arteritis[6] * Temporal arteritis[6] * Other * Obstructive sleep apnea[6] * Gastroesophageal reflux disease[6] * Chronic fatigue syndrome[6] * Fibromyalgia * Granulomatous disease[6] * Chronic eosinophilic pneumonia[6] * Lymphoid hyperplasia[6] * Diabetes insipidus[6] * Prinzmetal's angina[6] * Anxiety[6] * Pregnancy[6] * Drugs * Antipyretics (salicylates, acetaminophen)[6] * Antihypertensives[6] * Anabolic–androgenic steroids, in particular trenbolone, and the nandrolones[6] * Dinitrophenol \- a common side effect * Phenothiazines[6] * Drug withdrawal: ethanol, benzodiazepines, heroin (and other opioids), * Over-bundling[6] * Autonomic over-activity[6] * Inflammatory bowel disease (IBD) - Crohn's disease/ulcerative colitis ## References[edit] 1. ^ "Hyperhidrosis - MeSH - NCBI". www.ncbi.nlm.nih.gov. Retrieved 29 October 2020. 2. ^ a b "Night sweats - Mayo Clinic". www.mayoclinic.org. Retrieved 29 October 2020. 3. ^ T. F. Kruger; M. H. Botha (2008). Clinical Gynaecology. Juta and Company Ltd. p. 333. ISBN 978-0-7021-7305-9. 4. ^ Bansal, Ramandeep; Aggarwal, Neelam (January–March 2019). "Menopausal Hot Flashes: A Concise Review". Journal of Mid-Life Health. 10 (1): 6–13. doi:10.4103/jmh.JMH_7_19. ISSN 0976-7800. PMC 6459071. PMID 31001050. 5. ^ a b Mold, James W.; Holtzclaw, Barbara J.; McCarthy, Laine (November–December 2012). "Night sweats: a systematic review of the literature". Journal of the American Board of Family Medicine: JABFM. 25 (6): 878–893. doi:10.3122/jabfm.2012.06.120033. ISSN 1558-7118. PMID 23136329. S2CID 24179827. 6. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af Viera, Anthony J.; Bond, Michael M.; Yates, Scott W. (1 March 2003). "Diagnosing Night Sweats". American Family Physician. 67 (5): 1019–1024. PMID 12643362. Retrieved 13 June 2012. 7. ^ a b c Jonathan E. Teitelbaum; Kathleen O. DeAntonis; Scott Kahan (2004). In a page: Pediatric signs & symptoms. Lippincott Williams & Wilkins. p. 6. ISBN 978-1-4051-0427-2. 8. ^ Tao Le; Vikas Bhushan (2006). First Aid for the USMLE Step 2 CS. McGraw-Hill Professional. p. 74. ISBN 978-0-07-147058-2. 9. ^ "Night sweats : Causes". Mayo Clinic. 22 March 2011. Retrieved 10 May 2012. 10. ^ Deecher, D. C.; K. Dorries (2007). "Understanding the pathophysiology of vasomotor symptoms (hot flushes and night sweats) that occur in perimenopause, menopause, and postmenopause life stages". Archives of Women's Mental Health. 10 (6): 247–257. doi:10.1007/s00737-007-0209-5. PMID 18074100. S2CID 21865706. ## External links[edit] Classification D * ICD-10: R61 * ICD-9-CM: 780.8, 327 * v * t * e Symptoms and signs that are general or constitutional Temperature heat * Fever * of unknown origin * drug-induced * postoperative * Hyperthermia * Hyperhidrosis * Night sweats cold * Chills * Hypothermia Aches and pains * Headache * Chronic pain * Cancer pain * Myalgia * Tenderness Malaise and fatigue * Lassitude * Lethargy * Atrophy * of muscle * Debility (or asthenia) Miscellaneous * Cachexia * Anorexia * Polyphagia and polydipsia * Flu-like 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	Night sweats	c0028081	29,824	wikipedia	https://en.wikipedia.org/wiki/Night_sweats	2021-01-18T18:41:03	{"umls": ["C0028081"], "wikidata": ["Q474718"]}
Cerebrotendinous xanthomatosis is a disorder characterized by abnormal storage of fats (lipids) in many areas of the body. People with this disorder cannot break down certain lipids effectively, specifically different forms of cholesterol, so these fats accumulate in the body in the form of fatty yellow nodules called xanthomas. These xanthomas are most commonly found in the brain and in connective tissue called tendons that attach muscle to bone, which is reflected in the condition name (cerebro- meaning brain and -tendinous referring to tendons). People with cerebrotendinous xanthomatosis often develop neurological problems in early adulthood that are thought to be caused by an abnormal accumulation of fats and an increasing number of xanthomas in the brain. These neurological problems include recurrent seizures (epilepsy), movement disorders, impaired speech (dysarthria), loss of sensation in the arms and legs (peripheral neuropathy), decline in intellectual function (dementia), hallucinations, and depression. Xanthomas can accumulate in the fatty substance that insulates and protects nerves (myelin), causing the destruction of myelin and disrupting nerve signaling in the brain. Degeneration (atrophy) of brain tissue caused by excess lipid deposits also contributes to the neurological problems. Xanthomas in the tendons begin to form in early adulthood. The most common areas for xanthomas to develop are tendons in the hands, elbows, knees, neck, and in the Achilles tendon, which connects the heel of the foot to the calf muscles in the leg. Tendon xanthomas may cause discomfort and interfere with tendon flexibility. While many affected people develop tendon xanthomas, these nodules may not be easily visible underneath the skin. Other features of cerebrotendinous xanthomatosis include clouding of the lenses of the eyes (cataracts) and chronic diarrhea in childhood; a reduced ability to produce and release a digestive fluid called bile (cholestasis), which can lead to a yellowing of the skin or whites of the eyes (jaundice); and progressively brittle bones that are prone to fracture (osteoporosis). People with cerebrotendinous xanthomatosis are also at an increased risk of developing cardiovascular disease or respiratory failure because of lipid accumulation in the heart or lungs, respectively. If untreated, the signs and symptoms related to cerebrotendinous xanthomatosis worsen over time; however, this condition varies greatly among those who are affected. ## Frequency The incidence of cerebrotendinous xanthomatosis is estimated to be 1 per million individuals worldwide. This condition is more common in the Moroccan Jewish population with an incidence of 1 in 108 individuals. ## Causes Mutations in the CYP27A1 gene cause cerebrotendinous xanthomatosis. The CYP27A1 gene provides instructions for producing an enzyme called sterol 27-hydroxylase. This enzyme works in the pathway that breaks down cholesterol to form acids used in the digestion of fats (bile acids), specifically a bile acid called chenodeoxycholic acid. Mutations in the CYP27A1 gene lead to the production of a nonfunction or abnormal sterol 27-hydroxylase that cannot help form chenodeoxycholic acid. As a result, other molecules are formed by an alternative pathway. A molecule called cholestanol, which is similar to cholesterol, is produced as well as substances called bile alcohols. Cholestanol and bile alcohols are increased in the blood, while blood cholesterol levels are typically normal. In various tissues in the body, including the brain and heart, cholesterol and cholestanol levels are increased. These lipids make up much of the fats found in xanthomas. The accumulation of cholesterol and cholestanol throughout the body's tissues causes the signs and symptoms of cerebrotendinous xanthomatosis. ### Learn more about the gene associated with Cerebrotendinous xanthomatosis * CYP27A1 ## 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	Cerebrotendinous xanthomatosis	c0238052	29,825	medlineplus	https://medlineplus.gov/genetics/condition/cerebrotendinous-xanthomatosis/	2021-01-27T08:24:53	{"gard": ["5622"], "mesh": ["D019294"], "omim": ["213700"], "synonyms": []}
Partington syndrome is a neurological disorder that causes intellectual disability along with a condition called focal dystonia that particularly affects movement of the hands. Partington syndrome usually occurs in males; when it occurs in females, the signs and symptoms are often less severe. The intellectual disability associated with Partington syndrome usually ranges from mild to moderate. Some affected individuals have characteristics of autism spectrum disorders that affect communication and social interaction. Recurrent seizures (epilepsy) may also occur in Partington syndrome. Focal dystonia of the hands is a feature that distinguishes Partington syndrome from other intellectual disability syndromes. Dystonias are a group of movement problems characterized by involuntary, sustained muscle contractions; tremors; and other uncontrolled movements. The term "focal" refers to a type of dystonia that affects a single part of the body, in this case the hands. In Partington syndrome, focal dystonia of the hands, which is called the Partington sign, begins in early childhood and gradually gets worse. This condition typically causes difficulty with grasping movements or using a pen or pencil. People with Partington syndrome may also have dystonia affecting other parts of the body; dystonia affecting the muscles in the face and those involved in speech may cause impaired speech (dysarthria). People with this disorder may also have an awkward way of walking (gait). Signs and symptoms can vary widely, even within the same family. ## Frequency The prevalence of Partington syndrome is unknown. At least 20 cases have been described in the medical literature. ## Causes Partington syndrome is caused by mutations in the ARX gene. This gene provides instructions for producing a protein that regulates the activity of other genes. Within the developing brain, the ARX protein is involved with movement (migration) and communication of nerve cells (neurons). In particular, this protein regulates genes that play a role in the migration of specialized neurons (interneurons) to their proper location. Interneurons relay signals between other neurons. The normal ARX protein contains four regions where a protein building block (amino acid) called alanine is repeated multiple times. These stretches of alanines are known as polyalanine tracts. The most common mutation that causes Partington syndrome, a duplication of genetic material written as c.428_451dup, adds extra alanines to the second polyalanine tract in the ARX protein. This type of mutation is called a polyalanine repeat expansion. The expansion likely impairs ARX protein function and may disrupt normal interneuron migration in the developing brain, leading to the intellectual disability and dystonia characteristic of Partington syndrome. ### Learn more about the gene associated with Partington syndrome * ARX ## Inheritance Pattern This condition is inherited in an X-linked recessive 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), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. Females with one altered copy of the gene may have some signs and symptoms related to the condition. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. Rarely, the genetic change that causes Partington syndrome is not inherited but occurs at some point during embryonic development. As cells continue to grow and divide, some of these cells will have the genetic change, and others will not (a situation known as mosaicism). The mosaic nature of these genetic changes lead to relatively mild features of Partington syndrome. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Partington syndrome	c0796250	29,826	medlineplus	https://medlineplus.gov/genetics/condition/partington-syndrome/	2021-01-27T08:24:55	{"gard": ["4235"], "mesh": ["C536300"], "omim": ["309510"], "synonyms": []}
Polysubstance dependence Psychoactive drugs SpecialtyPsychiatry Polysubstance dependence refers to a type of substance dependence disorder in which an individual uses at least three different classes of substances indiscriminately and does not have a favorite drug that qualifies for dependence on its own. Although any combination of three drugs can be used, studies have shown that alcohol is commonly used with another substance.[1] This is supported by one study on polysubstance use that separated participants who used multiple substances into groups based on their preferred drug. The results of a long-term or longitudinal study on substance use led the researchers to observe that excessively using or relying on one drug increased the probability of excessively using or relying on another drug.[2] ## Contents * 1 Common combinations * 2 Presentation * 2.1 Associated cognitive impairments * 2.1.1 Learning ability * 2.1.2 Memory, reasoning and decision making * 2.1.3 Length of abstinence matter * 3 Causes * 3.1 Biological * 3.2 Psychological * 3.3 Sociocultural * 4 Comorbidity of mental disorders * 4.1 Depression * 4.2 Eating disorders * 5 Diagnosis * 6 Treatment * 6.1 Inpatient treatment center * 6.2 Outpatient treatments * 6.3 Twelve-step programs * 6.4 Cognitive behavioral therapy * 6.5 Medications * 6.6 Medications that aid in treating addictions * 7 Epidemiology * 7.1 Gender differences * 8 See also * 9 References * 10 External links ## Common combinations[edit] The three substances were cocaine, alcohol, and heroin, which implies that those three are very popular.[3] Other studies have found that opiates, cannabis, amphetamines, hallucinogens, inhalants and benzodiazepines are often used in combination as well.[4] ## Presentation[edit] ### Associated cognitive impairments[edit] Cognition refers to what happens in the mind, such as mental functions like "perception, attention, memory, language, problem solving, reasoning, and decision making."[5] Although many studies have looked at cognitive impairments of individuals who are dependent on one drug, there are few researchers who have tried to determine the problems with cognitive functioning that are caused by dependence on multiple substances.[6] Therefore, what is known about the effects of polysubstance dependence on mental abilities is based on the results of a few studies. #### Learning ability[edit] The effect of polysubstance dependence on learning ability is one area of interest to researchers. A study involving 63 polysubstance dependent women and 46 controls (participants who were not using drugs) used the Benton Visual Retention Test (BVRT) and the California Verbal Learning Test (CVLT) to look at visual memory and verbal ability.[7] This study showed that in polysubstance dependent women, verbal learning ability was significantly decreased, though visual memory was not affected. In addition, alcohol and cocaine use led to more severe issues with verbal learning, recall, and recognition.[7] #### Memory, reasoning and decision making[edit] Sometimes studies about specific groups in the general population can be informative. One study decided to test the cognitive abilities of participants in rave parties who used multiple substances. To do this, they compared 25 rave party attenders with 27 control participants who were not using drugs. The results of this study indicated that in general, the rave attender group did not perform as well on tasks that tested speed of information processing, working memory, knowledge of similarities between words, ability to attend to a task with interference in the background, and decision making.[3] Certain drugs were associated with particular mental functions, but the researchers suggested that the impairments for working memory and reasoning were caused by the misuse of multiple substances.[3] Another study that tried to find differences between the effects of particular drugs focused on polysubstance users who were seeking treatment for addictions to cannabis, cocaine, and heroin. They studied a group of polysubstance users and a group that was not dependent on any drugs. Because alcohol was a common co-substance for nearly all of the polysubstance user group, it was difficult to tell exactly which drugs were affecting certain cognitive functions. The researchers found that the difference in the two groups' performance levels on executive function, or higher-level cognitive processing tasks were consistently showing that the polysubstance group scored lower than the control group.[8] In general, this meant that multiple substances negatively affected the polysubstance group's cognitive functioning. More specifically, the researchers found that the amount of cannabis and cocaine affected the verbal part of working memory, the reasoning task, and decision making, while cocaine and heroin had a similar negative effect on visual and spatial tasks, but cannabis particularly affected visual and spatial working memory.[8] These results suggest that the combined use of cannabis, cocaine, and heroin impair more cognitive functions more severely than if used separately.[8] Alcohol's negative effects on learning, spatial abilities and memory has been shown in many studies.[9] This raises a question: does using alcohol in combination with other substances impair cognitive functioning even more? One study decided to try to determine if polysubstance users who also abused alcohol would display poorer performance on a verbal learning and memory test in comparison to those who abused alcohol specifically.[10] The California Verbal Learning Test (CVLT) was used due to its ability to "quantify small changes in verbal learning and memory" by evaluating errors made during the test and the strategies used to make those errors.[10] The results of this study showed that the group of polysubstance and alcohol abusers did perform poorly on the CVLT recall and recognition tests in comparison to the group of alcohol abusers only, which implies that alcohol and drug abuse combined impaired the memory and learning of the group of polysubstance and alcohol abusers in a different way than the effects of alcohol alone can explain.[10] #### Length of abstinence matter[edit] Does abstinence for long periods of time help polysubstance dependent individuals to recover cognitive functioning? To examine this question, a group of researchers tested 207 polysubstance dependent men, of whom 73.4% were dependent on three or more drugs.[6] The researchers were interested in 6 areas of cognitive functioning, which included visual memory, verbal memory, knowledge of words, abstract reasoning, inhibition (interference), and attention.[6] The study used the Benton Visual Retention Test (BVRT) for testing visual memory, the California Verbal Learning Test (CVLT) for verbal memory, the Wechsler Adult Intelligence Scale vocabulary portion for knowledge of words, the Booklet Category Test for abstract reasoning, the Stroop Neuropsychological Screening task for inhibition, and the Trail Making Test for attention.[6] The results showed that neuropsychological ability did not improve with increases in the length of time abstinent. This suggests that polysubstance dependence leads to serious impairment which cannot be recovered much over the span of a year.[6] ## Causes[edit] ### Biological[edit] There is data to support that some genes contribute to substance dependence.[11] Some studies have focused on finding genes that predispose the person to be dependent on marijuana, cocaine, or heroin by studying genes that control a person's dopamine and opioid receptors, but no conclusive findings were reported.[12] Other researchers found a connection between dopamine receptor genes and dependency on a substance.[12] A potential problem with this study was that alcohol is commonly used with another substance, so the results of the study may not have been caused by dependency on a single substance. This means that multiple substances may have been contributing to the results, but the researchers suggested that further research should be done.[12] However, there are studies that have found evidence of the influence of genes on vulnerability to substance dependence.[13] These studies often use genotype, or the genetic information found on a person's chromosomes, and phenotype, which consists of the visible features of a person, to look at genetic patterns.[14] One study examined the phenotype and genotype of 1,858 participants from 893 families to look at differences in three nicotinic acetylcholine receptor genes found within these individuals.[13] The experimenters found significant connections between receptor genes for nicotine and polysubstance dependence, which indicated that differences in these genes can create the risk of being dependent on multiple substances.[13] ### Psychological[edit] A 1989 study conducted by Khantzian and Treece found that nearly 60% of their opioid-dependent sample met criteria for an Axis II diagnosis. In the same study, 93% of the sample had a comorbid disorder, implying that the comorbid disorder plays some role in the addiction.[15] It has also been shown that depression and polysubstance dependence are often both present at the same time. If a person is genetically predisposed to be depressed then they are at a higher risk of having polysubstance dependence.[16] Possibly the most widely accepted cause of addictions is the self-medication hypothesis, that views drug addiction as a form of coping with stress through negative reinforcement, by temporarily alleviating awareness of or concerns over the stressor.[17] Substance users learn that the effects of each type of drug work to relieve or better painful states. They use drugs as a form of self-medication to deal with difficulties of self-esteem, relationships, and self-care. Individuals with substance use disorders often are overwhelmed with emotions and painful situations and turn to substances as a coping method.[18] ### Sociocultural[edit] The sociocultural causes are areas in a person’s life that might have influenced their decision to start and continue using multiple substances. Sociocultural causes can be divided into social causes and cultural causes. * Social Causes: Some studies have shown that adolescents have one of the highest rates of polysubstance dependence. According to one study this population, ages 12–25, represents about half of the nation's illicit drug users. Of these illicit drug users, half of them have started using substances by the end of 12th grade. This could be attributed to social expectations of peers, peer pressure to fit it, or a way of numbing their emotions. Some of these young kids start trying different drugs initially to fit in, but then after a while they start to develop a tolerance for these substances and experience withdrawal if they don’t have enough substances in their system and eventually become dependent on having the effects of substance dependence. With tolerance comes the craving for additional drugs to get high, this constant need for that feeling is polysubstance dependence.[19] In the older generations, polysubstance dependence had been linked to additional considerations such as personality disorder, homelessness, bipolar disorder, major depressive disorder and so on. Medical care being so expensive and difficult to get long term has been linked to polysubstance dependence. Those who need psychological help sometimes use multiple substances as a type of self medication to help manage their mental illnesses.[19] ## Comorbidity of mental disorders[edit] For most of these disorders, in relation to polysubstance dependence, there is a vicious cycle that those with a dependence go through. First, Ingesting the drug creates a need for more, which creates a dopamine surge, which then creates pleasure. As the dopamine subsides, the pleasure adds to the emotional and physical pain and triggers stress transmitters, which in turn creates a craving, which must then be medicated, and thus the cycle begins again. However, the next time they use, more of the drug will need to be used to get to the same degree of intoxication .[20][21] ### Depression[edit] Scientists have hypothesized that the use of a drug either causes a mood disorder such as depression or at least attributes to a pre-existing one. Additionally, the substances that sufferers of depression use can be a misguided method of self-medication in order to manage their depression.[22] This is the classic chicken or egg hypothesis, does the pre-existing condition cause dependence or does dependence cause the condition? The underlying mental illness needs to be identified and treated in conjunction with treating the polysubstance dependence in order to increase the success rate of treatment and decrease the probability of relapse.[16] One specific study focused on alcohol and depression, because they are so commonly inter-related. Researchers have discovered that depression continues for several weeks after a patient had been rehabilitated and those who relapsed developed depression again. This means that the onset of depression happens after alcohol dependence occurs, which means that alcohol is a major contributor to depression.[16] ### Eating disorders[edit] One study showed that patients who are recovering from an addiction, who have had an eating disorder in the past, often use food to try to replace the substance that they are no longer getting. Or they obsess over controlling their weight and appearance. Some rehabilitation centers have licensed nutritionists to help patients develop healthy eating habits to help them cope while recovering from their addictions. It is important that those who have a former eating disorder be taught how to eat healthfully, so they don’t continuously switch from one addiction back to another.[21] ## Diagnosis[edit] According to the DSM-IV, a diagnosis of polysubstance dependence must include a person who has used at least three different substances (not including caffeine or nicotine) indiscriminately, but does not have a preference to any specific one. In addition they must show a minimum of three of the following symptoms listed below, all within the past twelve months.[23] There is a distinct difference between a person having three separate dependence issues and having Polysubstance dependence the main difference is polysubstance dependence means that they are not specifically addicted to one particular substance. This is often confused with multiple specific dependences present at the same time. To elaborate, if a person is addicted to three separate substance such as cocaine, methamphetamines and alcohol and is dependent on all three then they would be diagnosed with three separate dependence disorders existing together (cocaine dependence, methamphetamine dependence and alcohol dependence,) not polysubstance dependence.[23] In addition to using three different substances without a preference to one, there has to be a certain level of dysfunction in a person’s life to qualify for a diagnosis of polysubstance dependence.[24] One of the bigger challenges that often occurs when trying to diagnose is the fact that people don't always report what they are taking because they are afraid of getting into legal trouble.[19] When coding polysubstance Dependence in a DSM-IV it would be a multiaxial diagnosis 304.80- Polysubstance Dependence", next to the classification, it is accompanied by a list of other types of Substance dependence (e.g. "305.00 Alcohol Abuse" or "305.60 Cocaine Abuse").[25] The DSM-IV requires at least three of the following symptoms present during a 12-month period for a diagnoses of polysubstance dependence.[26] * Tolerance: Use of increasingly high amounts of a substance or they find the same amount less and less effective ( the amount has to be at least 50% more of the original amount needed.) * Withdrawal: Either withdrawal symptoms when drug stops being used or the drug is used to prevent withdrawal symptoms. * Loss of control: Repeated use of more drugs than planned or use of the drugs over longer periods of time than planned. * Inability to stop using: Either unsuccessfully attempted to cut down or stop using the drugs or a persistent desire to stop using. * Time: Spending a lot of time studying drugs, obtaining drugs, using drugs, being under the influence of drugs, and recovering from the effects of drugs. * Interference with activities: Give up or reduce the amount of time involved in recreational activities, social activities, and/or occupational activities because of the use of drugs. * Harm to self: Continuous use of drugs despite having a physical or psychological problem caused by or made worse by the use of drugs.[26] DSM-5 eliminated polysubstance disorder; there the drugs must be specified, among other related changes.[27] ## Treatment[edit] Treatment for polysubstance dependence has many critical aspects. Drug rehabilitation is a lengthy and difficult process. Treatment must be individualized and last a sufficient amount of time to ensure the patient has kicked the addictions and to ensure the prevention of relapse. The most common forms of treatment for polysubstance dependence include: inpatient and outpatient treatment centers, counseling and behavioral treatments, and medications. It is important that treatments be carried on throughout the patient’s life in order to prevent relapse. It is a good idea that recovering addicts continue to attend social support groups or meet with counselors to ensure they do not relapse.[28] ### Inpatient treatment center[edit] Inpatient treatment centers are treatment centers where addicts move to the facility while they are undergoing treatment. Inpatient treatment centers offer a safe environment where patients will not be exposed to potentially harmful situations during their treatments as they would on the outside. Inpatients usually undergo the process of detoxification. Detox involves withdrawing the user (usually medically) from all substances of concern. During their stay in the treatment facility, patients often are learning to manage and identify their drug addictions and to find alternate ways to cope with whatever is the cause of their addiction.[29] ### Outpatient treatments[edit] Outpatient treatments include many of the same activities offered in an inpatient treatment facility,[30] but the patient is not protected by the secure and safe environment of an inpatient treatment center. For this reason, they are significantly less effective. The patient usually continues to hold a job and goes to treatment nightly.[29] ### Twelve-step programs[edit] Both in-patient and out-patient treatments can offer introductions to 12-step programs. Suggested 12-step programs are Alcoholics Anonymous (AA) and Narcotics Anonymous (NA). They offer regular meetings where members can discuss their experiences in a non-judgmental and supportive place.[31] ### Cognitive behavioral therapy[edit] Also offered to patients are one-on-one counseling sessions and cognitive behavioral therapy(CBT).[29] When looked at through a cognitive-behavioral perspective, addictions are the result of learned behaviors developed through positive experiences. In other words, when an individual uses a drug and receives desired results (happiness, reduced stress, etc.) it may become the preferred way of attaining those results, leading to addictions. The goal of CBT is to identify the needs that the addictions are being used to meet and to develop skills and alternative ways of meeting those needs. The therapist will work with the patient to educate them on their addictions and give them the skills they need to change their cognition's and behaviors.Addicts will learn to identify and correct problematic behavior. They will be taught how to identify harmful thoughts and drug cravings. CBT is an effective treatment for addictions.[32] ### Medications[edit] Medications can be very helpful in the long term treatment of polysubstance dependence. Medications are a useful aid in helping to prevent or reducing drug cravings. Another benefit of medications is helping to preventing relapse. Since drug addictions effect brain functioning, medications assist in returning to normal brain functioning. Polysubstance abusers require medications for each substance they are addicted to, as the current medications do not treat all addictions simultaneously. Medications are a useful aid in treatments, but are not effective when they are the sole treatment method.[28] ### Medications that aid in treating addictions[edit] * Methadone treatment for heroin addiction.[33] * 'Naltrexone: Reduces opiates and alcohol cravings. * Disulfiram: induces intense nausea after drinking alcohol. * Acamprosate:normalizes brain chemistry disrupted by alcohol withdrawal and aids alcohol abstinence. * Buprenorphine/naloxone: The two drugs together reduce cravings and block the pleasure from opiates.[34] ## Epidemiology[edit] There are not very many studies that have examined how often polysubstance dependence occurs or how many people are dependent on multiple substances. However, according to a study that analyzed the results from the National Epidemiological Survey on Alcohol and Related Conditions, approximately 215.5 out of a total of 43,093 individuals in the United States (0.5%) met the requirements for polysubstance abuse/dependence.[35] Another study suggested that the number of new cases of polysubstance dependence has been going up.[36] This idea was supported by a study that took place in Munich, Germany. A group of researchers chose to look at responses to a survey using the M-Composite International Diagnostic Interview (M-CIDI). The M-CIDI is a version of the Composite International Diagnostic Interview (CIDI).[37] The researchers collected data from 3,021 participants, all between the ages of 14 and 24, to estimate the prevalence, or total number of cases, of drug abuse/dependence and of polysubstance abuse/dependence.[38] The results of this study indicated that of the 17.3% who said that they regularly used drugs, 40% said that they used more than one substance, but 3.9% specifically reported using three or more substances, indicating that there is a lot of overlap in the use of different substances.[38] The researchers compared their results to earlier German studies and found that substance dependence seems to be increasing, at least in Germany.[38] ### Gender differences[edit] Women and men differ in various ways when it comes to addictions. Research has shown that women are more likely to be polysubstant dependent. It has been noted that a larger percentage of women abuse licit (legal) drugs such as tranquilizers, sedatives, and stimulants. On the other hand, men are more likely to abuse illicit (illegal) drugs such as cocaine, meth, and other street drugs. Research suggests that women addicts more frequently have a family history of drug abuse. When asked to describe their onset of addictions, women more frequently describe their addiction as sudden where as men describe them as gradual. Females have a higher percentage of fatty tissues and a lower percentage of body water than men. Therefore, women have slower absorption rates of drug substances. This means these substances are at a higher concentration in a women’s bloodstream. Women addicts are known to be at greater risk for fatty liver disease, hypertension, anemia, and other disorders.[39] ## See also[edit] * Self-medication ## References[edit] 1. ^ Malcolm, Barris P.; Hesselbrock, Michie N.; Segal, Bernard (2006). "Multiple Substance Dependence and Course of Alcoholism among Alaska Native Men and Women". Substance Use & Misuse. 41 (5): 729–41. doi:10.1080/10826080500391803. PMID 16603457. S2CID 33406853. 2. ^ Newcomb, Michael D.; Galaif, Elisha R.; Locke, Thomas F. (2001). "Substance use diagnoses within a community sample of adults: Distinction, comorbidity, and progression over time". Professional Psychology: Research and Practice. 32 (3): 239–47. doi:10.1037/0735-7028.32.3.239. 3. ^ a b c Verdejo-García, Antonio; Pérez-García, Miguel (2006). "Profile of executive deficits in cocaine and heroin polysubstance users: Common and differential effects on separate executive components". Psychopharmacology. 190 (4): 517–30. doi:10.1007/s00213-006-0632-8. PMID 17136401. S2CID 38338649. 4. ^ Kornreich, Charles; Delle-Vigne, Dyna; Campanella, Salvatore; Noël, Xavier; Papageorgiou, Constantin; Brown, Olivier; Verbanck, Paul; Ermer, Elsa (2012). "Conditional reasoning difficulties in polysubstance-dependent patients". Psychology of Addictive Behaviors. 26 (3): 665–71. doi:10.1037/a0025841. PMID 21988481. 5. ^ Goldstein, E. Bruce (2008). "Cognitive psychology". Cognitive Psychology: Connecting Mind, Research, and Everyday Experience (2nd ed.). Belmont, CA: Wadsworth. p. 488. ISBN 978-0-495-09557-6. 6. ^ a b c d e Medina, K; Shear, PK; Schafer, J; Armstrong, TG; Dyer, P (2004). "Cognitive functioning and length of abstinence in polysubstance dependent men". Archives of Clinical Neuropsychology. 19 (2): 245–58. doi:10.1016/S0887-6177(03)00043-X. PMID 15010089. 7. ^ a b Medina KL, Shear PK, Schafer J (2006). "Memory functioning in polysubstance dependent women". Drug and Alcohol Dependence. 84 (3): 248–55. doi:10.1016/j.drugalcdep.2006.02.009. PMID 16595165. 8. ^ a b c Fernandez-Serrano, M. J.; Perez-Garcia, M.; Schmidt Rio-Valle, J.; Verdejo-Garcia, A. (2009). "Neuropsychological consequences of alcohol and drug abuse on different components of executive functions". Journal of Psychopharmacology. 24 (9): 1317–32. doi:10.1177/0269881109349841. PMID 20007413. S2CID 9084814. 9. ^ "Cognitive impairment and recovery from alcoholism". Alcohol Alert. National Institute on Alcohol Abuse and Alcoholism. July 2001. 10. ^ a b c Bondi, Mark W.; Drake, Angela I.; Grand, Igor (1998). "Verbal learning and memory in alcohol abusers and polysubstance abusers with concurrent alcohol abuse". Journal of the International Neuropsychological Society. 4 (4): 319–28. doi:10.1017/S1355617798003191. PMID 9656605. 11. ^ Uhl, George R.; Liu, Qing-Rong; Walther, Donna; Hess, Judith; Naiman, Daniel (2001). "Polysubstance Abuse–Vulnerability Genes: Genome Scans for Association, Using 1,004 Subjects and 1,494 Single-Nucleotide Polymorphisms". American Journal of Human Genetics. 69 (6): 1290–300. doi:10.1086/324467. PMC 1235541. PMID 11704927. 12. ^ a b c Reich, T; Hinrichs, A; Culverhouse, R; Bierut, L (1999). "Genetic Studies of Alcoholism and Substance Dependence". American Journal of Human Genetics. 65 (3): 599–605. doi:10.1086/302561. PMC 1377965. PMID 10441565. 13. ^ a b c Sherva, Richard; Kranzler, Henry R; Yu, Yi; Logue, Mark W; Poling, James; Arias, Albert J; Anton, Raymond F; Oslin, David; et al. (2010). "Variation in Nicotinic Acetylcholine Receptor Genes is Associated with Multiple Substance Dependence Phenotypes". Neuropsychopharmacology. 35 (9): 1921–31. doi:10.1038/npp.2010.64. PMC 3055642. PMID 20485328. 14. ^ Smith, Maree T. (September 2010). "Pharmacogenetics". Pain: Clinical Updates. 18 (8): 1–8. 15. ^ Hall, Danny H.; Queener, John E. (2007). "Self-Medication Hypothesis of Substance Use: Testing Khantzian's Updated Theory". Journal of Psychoactive Drugs. 39 (2): 151–8. doi:10.1080/02791072.2007.10399873. PMID 17703709. S2CID 25558656. 16. ^ a b c Swendsen, J; Merikangas, KR (2000). "The comorbidity of depression and substance use disorders". Clinical Psychology Review. 20 (2): 173–89. doi:10.1016/S0272-7358(99)00026-4. PMID 10721496. 17. ^ Khantzian, Edward J. (18 September 2008). Understanding Addiction as Self Medication: Finding Hope Behind the Pain. Lanham, Maryland: Rowman & Littlefield Publishers. pp. 113. ISBN 978-0-7425-6137-3. 18. ^ Khantzian, Edward J. (1997). "The Self-Medication Hypothesis of Substance Use Disorders: A Reconsideration and Recent Applications". Harvard Review of Psychiatry. 4 (5): 231–44. doi:10.3109/10673229709030550. PMID 9385000. S2CID 39531697. 19. ^ a b c Troncale, Joseph A. (May 2004). "Understanding dynamics of polysubstance dependence". Addiction Professionals. 20. ^ Johnson, Jayne. "The Addicted Brain". Boca Raton, Florida: Wellness Resource Center.[unreliable medical source?] 21. ^ a b "Treatment Dual Diagnosis". Boca Raton, Florida: Wellness Resource Center.[unreliable medical source?] 22. ^ Abraham, Henry David; Fava, Maurizio (1999). "Order of onset of substance abuse and depression in a sample of depressed outpatients". Comprehensive Psychiatry. 40 (1): 44–50. doi:10.1016/S0010-440X(99)90076-7. PMID 9924877. 23. ^ a b "Practice-Relevant Changes to the DSM-IV-TR: Clarification of Concept of Polysubstance Dependence". American Psychiatric Association. Retrieved 2012-07-05. 24. ^ American Psychiatric Association (2000). Quick reference to the diagnostic criteria from DSM-IV-TR. The American Psychiatric Association. ISBN 978-0-89042-026-3.[page needed] 25. ^ Skodol, Andrew E.; Oldham, John M.; Gallaher, Peggy E. (1999). "Axis II Comorbidity of Substance Use Disorders Among Patients Referred for Treatment of Personality Disorders". The American Journal of Psychiatry. 156 (5): 733–8. doi:10.1176/ajp.156.5.733 (inactive 2020-12-16). PMID 10327906.CS1 maint: DOI inactive as of December 2020 (link) 26. ^ a b American Psychiatric Association (2000). Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition: DSM-IV-TR. American Psychiatric Pub. pp. 293–4. ISBN 978-0-89042-025-6. 27. ^ "Highlights of Changes from DSM-IV-TR to DSM-5" (PDF). American Psychiatric Publishing. American Psychiatric Association. 2013. p. 16. "The DSM-IV specifier for a physiological subtype has been eliminated in DSM-5, as has the DSM-IV diagnosis of polysubstance dependence." 28. ^ a b "Treatment Approaches for Drug Addiction". DrugFacts. NIDA. September 2009. 29. ^ a b c "What is Drug rehab?" drugrehab.org[full citation needed][unreliable medical source?] 30. ^ "Inpatient Rehab Facilities - Find Inpatient Rehab Near Me". Recovery.org. 2013-05-15. Retrieved 2020-11-13. 31. ^ Laudet, A.; Stanick, V.; Sands, B. (2007). "An Exploration of the Effect of On-Site 12-Step Meetings on Post-Treatment Outcomes among Polysubstance-Dependent Outpatient Clients". Evaluation Review. 31 (6): 613–46. doi:10.1177/0193841X07306745. PMC 2396509. PMID 17986710. 32. ^ Kadden, Ronald M. (9 October 2002). "Cognitive-Behavior Therapy for Substance Dependence: Coping Skills Training" (PDF). Archived from the original (PDF) on 5 January 2012.[unreliable medical source?] 33. ^ Purvis, Andrew (11 December 1989). "Medicine: Can drugs cure drug addiction?". Time. 34. ^ "Addiction Treatments Past and Present". Archived from the original on November 13, 2011. 35. ^ Agrawal, Arpana; Lynskey, Michael T.; Madden, Pamela A. F.; Bucholz, Kathleen K.; Heath, Andrew C. (2007). "A latent class analysis of illicit drug abuse/dependence: Results from the National Epidemiological Survey on Alcohol and Related Conditions". Addiction. 102 (1): 94–104. doi:10.1111/j.1360-0443.2006.01630.x. PMID 17207127. 36. ^ Suresh, Stelinas.D; Venkatesan, J (2008). "Substance dependence: Decades apart in a teaching hospital". Indian Journal of Psychiatry. 50 (2): 100–5. doi:10.4103/0019-5545.42396. PMC 2738335. PMID 19742216. 37. ^ Schumann, A. (2001). "The association between degree of nicotine dependence and other health behaviours: Findings from a German general population study". The European Journal of Public Health. 11 (4): 450–2. doi:10.1093/eurpub/11.4.450. PMID 11766489. 38. ^ a b c Perkonigg, Axel; Lieb, Roselind; Wittchen, Hans-Ulrich (1998). "Prevalence of Use, Abuse and Dependence of Illicit Drugs among Adolescents and Young Adults in a Community Sample". European Addiction Research. 4 (1–2): 58–66. doi:10.1159/000018923. PMID 9740818. S2CID 46220739. 39. ^ Nelson-Zlupko, Lani; Kauffman, Eda; Dore, Martha Morrison (1995). "Gender differences in drug addiction and treatment: Implications for social work intervention with substance-abusing women". Social Work. 40 (1): 45–54. doi:10.1093/sw/40.1.45. PMID 7863372. ## External links[edit] * A great resource for more information: http://www.nida.nih.gov/nidahome.html * v * t * e Combined substance use and adulteration Combined substance use * Active metabolite * Codrug * Combination drug * Combined drug intoxication * Drug interaction * Poly drug use * Polypharmacy * Polysubstance dependence * Prodrug * Synergy Adulteration * Contamination * Clandestine chemistry * Cutting agent * Diluent * Impurity * Lacing * Mickey Finn Harm reduction * Pill testing * Reagent testing [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Polysubstance dependence	c0032606	29,827	wikipedia	https://en.wikipedia.org/wiki/Polysubstance_dependence	2021-01-18T19:04:56	{"wikidata": ["Q7227004"]}
Malignant peripheral nerve sheath tumor (MPNST) is a rare and often aggressive soft tissue sarcoma occurring in a wide range of anatomical sites. ## Epidemiology Exact prevalence and incidence are unknown. Incidence of MPNST in the general population has been reported to be 1/100,000. MPNSTs account for about 5 to 10% of all soft tissue sarcomas. The sex ratio is about equal. Incidence among neurofibromatosis type 1 patients (NF1; see this term) is reported to be approximately 5 to 10%. ## Clinical description The age of occurrence is highly variable but most cases are reported in adults (typically between 20 and 50 years of age). In most cases, tumors arise in major nerve trunks such as the sciatic nerve or in the brachial plexus and sacral plexus. They are highly variable in appearance and commonly present as a rapidly enlarging palpable mass that is sometimes painful, with associated neurologic deficits such as radicular pain, paresthesia, and motor weakness. Tumors are fusiform to globular in shape, usually well circumscribed, and can be white to yellow and soft or firm. They occur most commonly in the trunk, head, neck and proximal extremities. Very rare anatomical sites include the brain, breast, posterior mediastinum, bladder, adrenal gland and skin. Tumors are often aggressive and high-grade, with the tendency to recur or to metastasize. MPNSTs can occur sporadically or in patients with NF1. They occur either de novo or from a preexisting neurofibroma or rarely from a schwannoma. ## Etiology The etiology is unknown. Identified gene alterations include loss of the NF1 (17q11.2) and TP53 tumor suppressor gene (17p13.1). About 10% of tumors are associated with prior therapeutic or environmental radiation exposure. ## Diagnostic methods Histopathological examination is needed for definitive diagnosis. Biopsy usually reveals MPNST to be an infiltrative neoplasm with a varied range of cell morphologies (spindle, rounded or fusiform cells), with cellular fascicles which alternate with myxoid regions (marbled pattern). Diagnosis may be challenging because there are no specific immunohistochemical or molecular markers. Radiological imaging is used to determine the site and extension of the tumor. ## Differential diagnosis Other malignant neoplasms to include in the differential diagnosis include synovial sarcoma, fibrosarcoma, undifferentiated pleomorphic sarcoma, angiosarcoma (see these terms), melanoma, and myoepithelial tumors. ## Management and treatment Total surgical resection is the mainstay of treatment. If removal is not possible, excision combined with high-dose radiation therapy may be used. Local Radiotherapy may be beneficial, but appears to have little effect on long-term survival. Chemotherapy is generally not effective. ## Prognosis Prognosis is generally poor and depends on the size of the tumor and success of treatment. A less favorable prognosis is associated with large tumors, NF1-associated cases, and truncal localization. The recurrence rate is reported to be as high as 40% and approximately two thirds of cases metastasize (lungs and bone). Five-year survival rate is reported to be 26% to 60%, and 10-year survival to be around 45%. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Malignant peripheral nerve sheath tumor	c0751690	29,828	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3148	2021-01-23T18:17:49	{"gard": ["10872", "8211"], "mesh": ["D018319"], "umls": ["C0206729", "C0751690"], "icd-10": ["C47.9"], "synonyms": ["MPNST", "Malignant neurilemmoma", "Malignant neurofibroma", "Malignant schwannoma", "Neurofibrosarcoma", "Neurogenic sarcoma"]}
## Summary ### Clinical characteristics. Huntington disease (HD) is a progressive disorder of motor, cognitive, and psychiatric disturbances. The mean age of onset is 35 to 44 years, and the median survival time is 15 to 18 years after onset. ### Diagnosis/testing. The diagnosis of HD rests on positive family history, characteristic clinical findings, and the detection of an expansion of 36 or more CAG trinucleotide repeats in HTT. ### Management. Treatment of manifestations: Pharmacologic therapy including typical neuroleptics (haloperidol), atypical neuroleptics (olanzapine), benzodiazepines, or the monoamine-depleting agent tetrabenazine for choreic movements; anti-parkinsonian agents for hypokinesia and rigidity; psychotropic drugs or some types of antiepileptic drugs for psychiatric disturbances (depression, psychotic symptoms, outbursts of aggression); valproic acid for myoclonic hyperkinesia. Supportive care with attention to nursing needs, dietary intake, special equipment, and eligibility for state and federal benefits. Prevention of secondary complications: Attention to the usual potential complications in persons requiring long-term supportive care and to side effects associated with pharmacologic treatments. Surveillance: Regular evaluations of the appearance and severity of chorea, rigidity, gait problems, depression, behavioral changes, and cognitive decline; routine assessment of functional abilities using the Behavior Observation Scale Huntington (BOSH) and the Unified Huntington's Disease Rating Scale (UHDRS). Agents/circumstances to avoid: L-dopa-containing compounds (may increase chorea), alcohol consumption, smoking. Other: Children and adolescents with a parent with HD may benefit from referral to a local HD support group for educational materials and psychological support. ### Genetic counseling. HD is inherited in an autosomal dominant manner. Offspring of an individual with a pathogenic variant have a 50% chance of inheriting the disease-causing allele. Predictive testing in asymptomatic adults at risk is available but requires careful thought (including pre- and post-test genetic counseling) as there is currently no cure for the disorder. However, asymptomatic individuals at risk may be eligible to participate in clinical trials. Predictive testing is not considered appropriate for asymptomatic at-risk individuals younger than age 18 years. Prenatal testing by molecular genetic testing and preimplantation genetic testing are possible. ## Diagnosis ### Suggestive Findings Huntington disease (HD) should be suspected in individuals with any of the following: * Progressive motor disability featuring chorea. Voluntary movement may also be affected. * Mental disturbances including cognitive decline, changes in personality, and/or depression * Family history consistent with autosomal dominant inheritance Note: The appearance and sequence of motor, cognitive, and psychiatric disturbances can be variable in HD (see Clinical Description). ### Establishing the Diagnosis The diagnosis of HD is established in a proband with clinical signs and symptoms of HD by the identification of a heterozygous abnormal CAG trinucleotide repeat expansion in HTT by molecular genetic testing (see Table 1). Note: Pathogenic (CAG)n repeat expansions in HTT cannot currently be detected by clinical sequence-based multigene panels, exome sequencing, or genome sequencing. CAG repeat sizes * Normal. 26 or fewer CAG repeats * Intermediate. Range from 27 to 35 CAG repeats. An individual with an allele in this range is not at risk of developing symptoms of HD but, because of instability in the CAG tract, may be at risk of having a child with an allele in the HD-causing range [Semaka et al 2006]. Risk estimates for germline CAG expansion have been established [Semaka et al 2013a, Semaka & Hayden 2014]. * Pathogenic HD-causing alleles. 36 or more CAG repeats. Persons who have an HD-causing allele are considered at risk of developing HD in their lifetime. HD-causing alleles are further classified as: * Reduced-penetrance HD-causing alleles. Range from 36 to 39 CAG repeats. An individual with an allele in this range is at risk for HD but may not develop symptoms. Elderly asymptomatic individuals with CAG repeats in this range are common [Kay et al 2016]. * Full-penetrance HD-causing alleles. 40 or more CAG repeats. Alleles of this size are associated with development of HD with increased certainty assuming a normal life span. Molecular genetic testing relies on targeted analysis to characterize the number of HTT CAG repeats. ### Table 1. Molecular Genetic Testing Used in Huntington Disease View in own window Gene 1Method 2, 3Proportion of Probands with a Pathogenic Variant Detectable by Method HTTTargeted analysis for CAG trinucleotide expansions100% 1\. See Table A. Genes and Databases for chromosome locus and protein name. 2\. See Table 6 for specific methods to characterize the number of CAG repeats in HTT. 3\. Current clinical sequence-based multigene panels, exome sequencing, and genome sequencing cannot detect pathogenic repeat expansions in this gene. Note: For comprehensive recommendations pertaining to predictive genetic testing for HD, see Genetic Counseling and MacLeod et al [2013]. ## Clinical Characteristics ### Clinical Description During the prodromal phase of Huntington disease (HD) individuals may have subtle changes in motor skills, cognition, and personality (see Figure 1) [Tabrizi et al 2013, Ross et al 2014, Liu et al 2015]. These subtle changes can occur as early as 15-20 years prior to the clinical onset of manifest HD. #### Figure 1. Natural history of Huntington disease (HD). Presymptomatic individuals are free from signs and symptoms of HD. During the prodromal phase, subtle signs and symptoms may be present prior to the diagnosis of HD, which is usually based on motor symptoms. (more...) Reilmann et al [2014] present guidelines for the diagnostic criteria of presymptomatic, prodromal, and manifest HD; see Table 2. This table can be used to place individuals into different diagnostic categories, which may have clinical management implications over time. For example, awareness of presymptomatic and prodromal HD may allow for preventive (rather than symptomatic) therapies. Note the clear differentiation of genetically confirmed HD in the classification system. ### Table 2. Categories of Huntington Disease Diagnosis View in own window HD ClassificationHD Signs/Symptoms Genetically ConfirmedNOT Genetically Confirmed Presymptomatic HD: HD, genetically confirmed, presymptomaticClinically at risk for HD: HD, not genetically confirmed, clinically at risk * No clinical motor signs/symptoms (motor DCL = 0 or 1) * No cognitive signs/symptoms * May have changes in imaging, quantitative motor assessments, or other biomarkers * No symptomatic treatment indicated * Disease-modifying treatment when safe & available Prodromal HD: HD, genetically confirmed, prodromalClinically prodromal HD: HD, not genetically confirmed, clinically prodromal * Subtle motor signs (usually motor DCL = 2) AND/OR subtle cognitive signs or symptoms * Minor decline from individual premorbid level of function possibly detectable, but not required & not detectable on TFC * Apathy or depression or other behavioral changes judged related to HD may be present. * Usually changes in imaging & quantitative motor assessments * May/may not require symptomatic treatment (e.g., for depression) * Disease-modifying treatment appropriate Manifest HD: HD, genetically confirmed, manifestClinically manifest HD: HD, not genetically confirmed, clinically manifest 1 * Presence of clinical motor &/or cognitive signs & symptoms that have an impact on life, with: * Functional changes (e.g., ↓ TFC); * Motor DCL = 3 or 4 (or motor DCL of 2 if cognitive changes significant AND evidence of progression) * Symptomatic & disease-modifying treatment appropriate Adapted from Reilmann et al [2014]; used with permission DCL = diagnostic confidence level (from the UHDRS rating scale); HD = Huntington disease; TFC = total functional capacity 1\. Requires motor DCL = 4, plus cognitive changes The mean age of onset for HD is approximately 45 years [Bates et al 2015]. About two thirds of affected individuals first present with neurologic manifestations; others present with psychiatric changes. In the early stages following diagnosis, manifestations include subtle changes in eye movements, coordination, minor involuntary movements, difficulty in mental planning, and often a depressed or irritable mood (see Table 3). Affected individuals are usually able to perform most of their ordinary activities and to continue working [Ross et al 2014, Bates et al 2015]. In approximately 25% of individuals with HD, the onset is delayed until after age 50 years, with some after age 70 years. These individuals have chorea, gait disturbances, and dysphagia, but a more prolonged and benign course than the typical individual. In the next stage, chorea becomes more prominent, voluntary activity becomes increasingly difficult, and dysarthria and dysphagia worsen. Most individuals are forced to give up their employment and depend increasingly on others for help, although they are still able to maintain a considerable degree of personal independence. The impairment is usually considerable, sometimes with intermittent outbursts of aggressive behaviors and social disinhibition. In late stages of HD, motor disability becomes severe and the individual is often totally dependent, mute, and incontinent. The median survival time after onset is 15 to 18 years (range: 5 to >25 years). The average age at death is 54 to 55 years [Bates et al 2015]. ### Table 3. Onset of Clinical Signs and Symptoms in HD View in own window Clinical Signs in HD Early * Clumsiness * Agitation * Irritability * Apathy * Anxiety * Disinhibition * Delusions * Hallucinations * Abnormal eye movements * Depression * Olfactory dysfunction Middle * Dystonia * Involuntary movements * Trouble w/balance & walking * Chorea, twisting & writhing motions, jerks, staggering, swaying, disjointed gait (can seem like intoxication) * Trouble w/activities that require manual dexterity * Slow voluntary movements; difficulty initiating movement * Inability to control speed & force of movement * Slow reaction time * General weakness * Weight loss * Speech difficulties * Stubbornness Late * Rigidity * Bradykinesia (difficulty initiating & continuing movements) * Severe chorea (less common) * Significant weight loss * Inability to walk * Inability to speak * Swallowing problems; danger of choking * Inability to care for oneself Abnormalities of movement. Disturbances of both involuntary and voluntary movements occur in individuals with HD. Chorea, an involuntary movement disorder consisting of nonrepetitive, nonperiodic jerking of limbs, face, or trunk, is the major sign of the disease. Chorea is present in more than 90% of individuals, and typically increases in severity during the first ten years. The choreic movements are continuously present during waking hours, cannot be suppressed voluntarily, and are worsened by stress. With advancing disease duration, other involuntary movements such as bradykinesia, rigidity, and dystonia occur. Impairment in voluntary motor function is an early sign. Affected individuals and their families describe clumsiness in common daily activities. Motor speed, fine motor control, and gait are affected. Oculomotor disturbances occur early and worsen progressively. Difficulty in initiating ocular saccades, slow and hypometric saccades, and problems in gaze fixation may be seen in up to 75% of symptomatic individuals [Blekher et al 2006, Golding et al 2006]. Dysarthria occurs early and is common. Dysphagia occurs in the late stages. Hyperreflexia occurs early in 90% of individuals, while clonus and extensor plantar responses occur late and less frequently. Abnormalities of cognition. A global and progressive decline in cognitive capabilities occurs in all individuals with HD. Cognitive changes include forgetfulness, slowness of thought processes, impaired visuospatial abilities, and impaired ability to manipulate acquired knowledge. Several studies have identified subtle but definite cognitive deficits prior to the onset of motor symptoms [Bourne et al 2006, Montoya et al 2006, Paulsen et al 2008, Tabrizi et al 2009, Rupp et al 2010]. The initial changes often involve loss of mental flexibility and impairment of executive functions such as mental planning and organization of sequential activities. Memory deficits with greater impairment for retrieval of information occur early, but verbal cues, priming, and sufficient time may lead to partial or correct recall. Early in the disease the memory deficits in HD are usually much less severe than in Alzheimer disease. The overall cognitive and behavioral syndrome in individuals with HD is more similar to frontotemporal dementia than to Alzheimer disease. Attention and concentration are involved early [Peinemann et al 2005], resulting in easy distractibility. Language functions are relatively preserved, but a diminished level of syntactic complexity, cortical speech abnormalities, paraphasic errors, and word-finding difficulties are common in late stages. Neuropsychologic testing reveals impaired visuospatial abilities, particularly in late stages of the disease. Lack of awareness, especially of one's own disabilities, is common [Ho et al 2006, Bates et al 2015]. Psychiatric disturbances. Individuals with HD develop significant personality changes, affective psychosis, or schizophrenic psychosis [Rosenblatt 2007]. Prior to onset of HD, they tend to score high on measures of depression, hostility, obsessive-compulsiveness, anxiety, and psychoticism [Duff et al 2007]. Unlike the progressive cognitive and motor disturbances, the psychiatric changes tend not to progress with disease severity [Epping et al 2016]. Behavioral disturbances such as intermittent explosiveness, apathy, aggression, alcohol abuse, sexual dysfunction and deviations, and increased appetite are frequent. Delusions, often paranoid, are common. Hallucinations are less common. Depression and suicide risk. The incidence of depression in preclinical and symptomatic individuals is more than twice that in the general population [Paulsen et al 2005b, Marshall et al 2007]. The etiology of depression in HD is unclear; it may be a pathologic rather than a psychological consequence of having the disease [Slaughter et al 2001, Pouladi et al 2009]. Suicide and suicide ideation are common in persons with HD, but the incidence rate changes with disease course and predictive testing results [Larsson et al 2006, Robins Wahlin 2007, van Duijn et al 2018]. The critical periods for suicide risk were found to be just prior to receiving a diagnosis and later, when affected individuals experience a loss of independence [Baliko et al 2004, Paulsen et al 2005a, Eddy et al 2016]. Other. Persons with HD tend to have a lower body mass index than controls [Pratley et al 2000, Stoy & McKay 2000, Djoussé et al 2002, Robbins et al 2006], which may be related to altered metabolism [Duan et al 2014] and could represent a biomarker of clinical progression [van der Burg et al 2017]. Individuals with HD also demonstrate disturbed cholesterol metabolism [Valenza & Cattaneo 2006, Wang et al 2014]. It is also common for persons with HD to demonstrate increased appetite and energy expenditure [Pratley et al 2000, Trejo et al 2004, Gaba et al 2005]. Sleep and circadian rhythms are disrupted in individuals with HD [Goodman & Barker 2010, Morton 2013], possibly as a result of hypothalamic dysfunction [Petersén & Björkqvist 2006] and/or alterations in melatonin secretion [Kalliolia et al 2014]. Insomnia and daytime somnolence may also be present, although this is more commonly due to psychiatric changes, depression, or chorea [Videnovic et al 2009]. Neuropathology. The primary neuropathologic feature of HD is degeneration of neurons in the caudate and putamen as well as the cerebral cortex [Waldvogel et al 2015]. The preferential degeneration of enkephalin-containing, medium spiny neurons of the indirect pathway of movement control in the basal ganglia provides the neurobiologic basis for chorea [Galvan et al 2012]. The additional loss of substance P-containing medium spiny neurons of the direct pathway results in akinesia and dystonia [Galvan et al 2012]. There is also evidence for loss of neurons in the globus pallidus, subthalamic nucleus, thalamus, hypothalamus, substantia nigra, and hippocampus [Vonsattel et al 1985, Vonsattel & DiFiglia 1998, Heinsen et al 1999, Petersén et al 2005, Guo et al 2012, Domínguez et al 2013, Singh-Bains et al 2016]. Region-specific patterns of neuronal loss in the basal ganglia and cortex may underlie the most evident symptoms in affected individuals and could contribute to the phenotypic variability among individuals [Thu et al 2010, Hadzi et al 2012, Kim et al 2014, Waldvogel et al 2015, Mehrabi et al 2016]. Pathology is also observed in peripheral tissues [Björkqvist et al 2008, van der Burg et al 2009]. Intraneuronal inclusions containing huntingtin, the protein expressed from HTT, are also a prominent neuropathologic feature of the disease. However, the expression of the huntingtin protein and the pattern and timing of huntingtin-containing inclusions in the brain do not correlate with the selective degeneration of the disease and are not believed to be primary determinants of pathology [Kuemmerle et al 1999, Michalik & Van Broeckhoven 2003, Arrasate et al 2004, Slow et al 2005, Slow et al 2006]. Neuroimaging. Imaging studies provide additional support for the clinical diagnosis of HD and are valuable tools for studying progression of the disease [Biglan et al 2009, Paulsen 2009, Tabrizi et al 2011, Tabrizi et al 2012, Tabrizi et al 2013]. In addition to significant striatal atrophy in symptomatic individuals, regional and whole-brain gray and white matter changes have been detected [Majid et al 2011, Tabrizi et al 2011, Tabrizi et al 2012, Tabrizi et al 2013]. Furthermore, MRI studies have revealed progressive gray and white matter atrophy many years prior to predicted disease onset [Tabrizi et al 2011, Tabrizi et al 2012, Tabrizi et al 2013]. Numerous studies in recent years have used neuroimaging to elucidate the clinical progression of HD, with the specific interest of using these objective measures in clinical trials for testing efficacy of experimental therapeutics [Tabrizi et al 2012, Tabrizi et al 2013]. Juvenile HD is defined by the onset of symptoms before age 20 years and accounts for 5%-10% of individuals with HD [Gonzalez-Alegre & Afifi 2006, Quarrell et al 2013]. The motor, cognitive, and psychiatric disturbances observed in adult HD are also observed in juvenile HD, but the clinical presentation of these disturbances is different. Severe mental deterioration, prominent motor and cerebellar symptoms, speech and language delay, and rapid decline are also characteristic of juvenile HD [Nance & Myers 2001, Gonzalez-Alegre & Afifi 2006, Squitieri et al 2006, Yoon et al 2006]. Epileptic seizures, unique to the youngest-onset group, are present in 30%-50% of those with onset of HD before age ten years [Gonzalez-Alegre & Afifi 2006]. In teenagers, symptoms are more similar to adult HD, in which chorea and severe behavioral disturbances are common initial manifestations [Nance & Myers 2001]. Intermediate alleles (IA). An individual with a CAG repeat in the 27-35 range is not believed to be at risk of developing HD but, because of instability in the CAG tract, may be at risk of having a child with an allele in the pathogenic CAG range [Semaka et al 2006, Kay et al 2018]. Limited data suggest that individuals with IAs may exhibit behavioral changes as well as motor and cognitive impairments, although more research is required in this regard [Killoran et al 2013, Cubo et al 2016]. ### Genotype-Phenotype Correlations A significant inverse correlation exists between the number of CAG repeats and the age of onset of HD [Langbehn et al 2004, Langbehn et al 2010]. See Molecular Genetics. * Individuals with adult onset of symptoms usually have an HTT allele with CAG repeats ranging from 36 to 55. * Individuals with juvenile onset of symptoms usually have an HTT allele with CAG repeats greater than 60. * Intermediate alleles (ranging from 27 to 35 CAG repeats) usually have not been associated with disease but are prone to CAG repeat instability [Semaka et al 2013b]. For data on the age-specific likelihood of onset by trinucleotide repeat size, see ubc.ca (pdf). In addition to age at clinical onset, CAG repeat length has also been shown to predict age at death, but not the duration of the illness [Keum et al 2016]. The rate of deterioration of motor, cognitive, and functional measures increases with larger CAG repeat sizes [Aziz et al 2009, Chao et al 2017]. The progression of behavioral symptoms appears not to be related to repeat size [Ravina et al 2008]. Homozygotes for fully penetrant HD alleles appear to have a similar age of onset to heterozygotes, but may exhibit an accelerated rate of disease progression [Squitieri et al 2011, Lee et al 2012]. A significant negative correlation also exists between CAG size and variability of onset, in which more variability in the late age of onset is associated with smaller CAG sizes, suggesting that non-CAG modifiers may have a greater effect at lower CAG sizes than at larger CAG sizes [Langbehn et al 2004, Gusella & Macdonald 2009]. On average, the CAG repeat size accounts for up to 70% of the variability in age of onset, with an estimated 10%-20% of the residual variability being accounted for by heritable factors [Li et al 2006, Gusella & Macdonald 2009]. Many genes at other loci have been shown to account for small amounts of this heritable portion of the variability [GeM-HD Consortium 2015]. Significant progress has been made in recent years in the identification of these additional genomic modifiers, both at the HTT locus and throughout the genome. * Cis-acting factors. The most common CAG repeat tract (>95% of alleles) has a CAA interruption in the penultimate repeat [(CAG)n-CAA-CAG]. Uninterrupted CAG repeats [(CAG)n] are associated with decreased age of onset in HD and increased somatic instability of the repeat [Ciosi et al 2019, GeM-HD Consortium 2019, Wright et al 2019] (GeM-HD 2019 full text). These findings suggest that uninterrupted CAG length is more predictive than polyglutamine length in estimating HD age of onset. * Trans-acting factors. Genome-wide association studies have identified other candidate modifier genes for HD [GeM-HD Consortium 2015, Moss et al 2017]. These analyses have shown the important role of biologic pathways involved in DNA repair, mitochondrial fission, and oxidoreductase activity with regard to this phenotype, and have identified candidate modifier genes for future study (e.g., FAN1, MLH1, MTMR10, MSH3, and RRM2B). ### Penetrance Alleles with 36 to 39 CAG repeats are considered HD-causing alleles, but exhibit incomplete penetrance. Elderly asymptomatic individuals with CAG repeats in this range are common [Kay et al 2016]. Disease risk varies for the common [(CAG)n-CAA-CAG] interrupted repeat, observed in more than 95% of alleles, and the rare [(CAG)n] uninterrupted repeat, observed in about 1% of alleles [Ciosi et al 2019, GeM-HD Consortium 2019, Wright et al 2019] (GeM-HD 2019 full text): * 36-39 repeats. Approximately one third of symptomatic individuals have a pure [(CAG)n] repeat. * 36 and 37 repeats. The majority of symptomatic individuals have a pure [(CAG)n] repeat. The loss of the CAA repeat has been termed the loss of interruption (LOI) variant [Wright et al 2019] and will be useful in modifying the probability of disease in individuals with 36-39 CAG repeats. Alleles that contain more than 40 CAG repeats are completely penetrant. No asymptomatic elderly individuals with alleles of more than 40 CAG repeats have been reported. ### Anticipation Anticipation, the phenomenon in which increasing disease severity or decreasing age of onset is observed in successive generations, is known to occur in HD. Anticipation occurs far more commonly in paternal transmission of the mutated allele. The phenomenon of anticipation arises from instability of the CAG repeat during spermatogenesis [Semaka et al 2013a]. Large expansions (i.e., an increase in allele size of >7 CAG repeats) occur almost exclusively through paternal transmission. Most often children with juvenile-onset disease inherit the expanded allele from their fathers, although on occasion they inherit it from their mothers [Nahhas et al 2005]. ### Nomenclature In the pre-molecular-genetic era, there were many different names for chorea, including St. Vitus's dance and Sydenham's chorea. Juvenile HD, or childhood-onset HD, was previously called the Westphal variant of HD. Individuals who do not yet show symptoms are in the premanifest phase of HD. Individuals who have been diagnosed with chorea and/or other validated signs of the disorder have manifest HD. ### Prevalence HD prevalence varies across world regions. Populations of European ancestry display an average prevalence of 9.71:100,000 [Rawlins et al 2016], but estimates as high as 17:100,000 have been reported [Fisher & Hayden 2014, Baig et al 2016]. In contrast, HD appears much less frequently in Japan, China, Korea, and Finland, as well as in indigenous African populations from South Africa, with estimated prevalence values ranging from 0.1:100,000 to 2:100,000 [Pringsheim et al 2012, Sipilä et al 2015, Xu & Wu 2015]. Individuals living in the Lake Maracaibo region of Venezuela are believed to have the highest prevalence of HD in the world [Wexler et al 2004]. The uneven distribution of HD is at least partially explained by the distribution of specific predisposing alleles and haplotypes in the general population of these ethnic groups [Warby et al 2009, Warby et al 2011, Kay et al 2018]. For example, a recent study of 15 diverse global populations demonstrated that the mean CAG size in a population, as well as intermediate allele frequency, correlates with HD prevalence and contributes to differences in disease prevalence across major ancestry groups [Kay et al 2018]. Reduced-penetrance HTT alleles (see Establishing the Diagnosis, CAG repeat sizes) have recently been shown to occur at a high frequency in the general population, with as many as one in 400 individuals having these alleles – although the penetrance rate was determined to be lower than previously reported (i.e., 0.2%-2% for 36-38 CAG alleles) [Kay et al 2016]. ## Differential Diagnosis Huntington disease (HD) falls into the differential diagnosis of chorea, dementia, and psychiatric disturbances. The differential diagnosis of several HD-like disorders is summarized here and reviewed elsewhere [Schneider et al 2007, Martino et al 2013]. The co-occurrence of Alzheimer disease and HD has also been reported [Davis et al 2014]. Noninherited conditions are associated with chorea, but most can be excluded easily in an individual with suspected HD based on associated findings and the course of illness. Causes of chorea include tardive dyskinesia, levodopa-induced dyskinesia, thyrotoxicosis, cerebrovascular disease, cerebral lupus, polycythemia, and group A beta-hemolytic Streptococcus. Inherited conditions. See Table 4. ### Table 4. Inherited Conditions to Consider in the Differential Diagnosis of Huntington Disease View in own window DisorderGene(s)MOIClinical Features of the Disorder Overlapping w/HDDistinguishing from HD Frontotemporal dementia &/or amyotrophic lateral sclerosisC9orf72AD * Movement disorders * Dementia * Psychiatric disturbances * Myoclonus * Tremor * Torticollis Huntington disease-like 1 (HDL1) (OMIM 603218) 1PRNPADRange of clinical features that overlap w/HD * Early onset * Slow progression Huntington disease-like 2 (HDL2)JPH3ADClinically indistinguishable from HDPrevalence highest among & perhaps exclusive to individuals of African descent Chorea-acanthocytosis (ChAc)VPS13AAR * Progressive movement disorder * Progressive cognitive & behavior changes * Myopathy * ↑ serum CK * Acanthocytosis * Seizures common * Mean age of onset ~30 yrs McLeod neuroacanthocytosis syndrome (MLS)XKXL * Cognitive impairment * Psychiatric symptoms * Acanthocytosis * Compensated hemolysis * McLeod blood group phenotype Spinocerebellar ataxia type 17 (SCA17)TBPAD * Chorea * Dementia * Psychiatric disturbances Cerebellar ataxia is the prominent movement disorder. Dentatorubral-pallidoluysian atrophy (DRPLA)ATN1AD * Progressive movement disorders & dementia * Psychiatric disturbances Ataxia & myoclonus are prominent movement disorders. Benign hereditary chorea (OMIM 118700)NKX2-1ADChorea * Nonprogressive chorea * Not assoc w/dementia Hereditary cerebellar ataxia (see Hereditary Ataxia Overview)ManyAD AR XLMovement disorderHereditary cerebellar ataxia assoc w/prominent cerebellar & long tract signs Familial Creutzfeld-Jakob disease (fCJD) (See Genetic Prion Disease.)PRNPAD * Typically late onset * Progressive dementia * Movement disorders * Behavior changes * Psychiatric symptoms * fCJD progresses more rapidly. * Myoclonus is a prominent involuntary movement. Early-onset familial Alzheimer diseaseAPP PSEN1 PSEN2ADDementiaNo movement disorders Familial frontotemporal dementia with parkinsonism-17MAPTAD * Late onset * Progressive movement disorders, dementia, & behavior changes * Psychiatric disturbances No chorea AD = autosomal dominant; AR = autosomal recessive; CNS = central nervous system; MOI = mode of inheritance; XL = X-linked 1\. HDL1 is caused by a specific pathogenic variant (8 extra octapeptide repeats) in the prion protein gene, PRNP, on chromosome 20p [Laplanche et al 1999, Moore et al 2001]. Similar pathogenic variants at this locus also result in other forms of prion disease such as familial Creutzfeldt-Jakob disease. The diagnosis of HD in children is straightforward in a family with a history of HD. In simplex cases (an affected individual with no known family history of HD), ataxia-telangiectasia, pantothenate kinase-associated neurodegeneration (previously known as Hallervorden-Spatz syndrome), Lesch-Nyhan syndrome, Wilson disease, progressive myoclonic epilepsy [Gambardella et al 2001], and other metabolic diseases must be excluded. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with Huntington disease (HD), the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended: * Physical examination * Neurologic assessment * Assessment of the full range of motor, cognitive, and psychiatric symptoms associated with HD. Among a range of clinical scoring systems that have been described, the Unified Huntington's Disease Rating Scale (UHDRS) provides a reliable and consistent assessment of the clinical features and progression of HD. * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations Pharmacologic therapy is limited to symptomatic treatment [Mestre et al 2009, Killoran & Biglan 2014]. * Choreic movements can be partially suppressed by typical (haloperidol) and atypical (olanzapine) neuroleptics; benzodiazepines; or the monoamine-depleting agent tetrabenazine [de Tommaso et al 2005, Bonelli & Wenning 2006, Huntington Study Group 2006]. Tetrabenazine can be effective as an antichoreic drug; however, its use is associated with severe adverse effects including extrapyramidal symptoms. Deutetrabenazine, a deuterated analog of tetrabenazine, has been modified by deuterium atom substitutions at specific sites on the molecule to increase half-life and systemic exposure [Stamler et al 2013]. These properties allow for less frequent dosing with fewer adverse effects [Frank et al 2016, Reilmann 2016]. * Anti-parkinsonian agents may ameliorate hypokinesia and rigidity, but may increase chorea. * Psychiatric disturbances such as depression, psychotic symptoms, and outbursts of aggression generally respond well to psychotropic drugs or some types of antiepileptic drugs. * Valproic acid has improved myoclonic hyperkinesia in Huntington disease [Saft et al 2006]. Supportive care with attention to nursing, diet, special equipment, and eligibility for state and federal benefits is much appreciated by individuals with HD and their families. Numerous social problems beset individuals with HD and their families; practical help, emotional support, and counseling can provide relief [Williams et al 2009]. ### Prevention of Secondary Complications Significant secondary complications of HD include the following: * The complications typically observed with any individual requiring long-term supportive care * The side effects associated with various pharmacologic treatments. Drug side effects are dependent on a variety of factors including the compound involved, the dosage, and the individual; with the medications typically used in HD, side effects may include depression, sedation, nausea, restlessness, headache, neutropenia, and tardive dyskinesia. For some individuals, the side effects of certain therapeutics may be worse than the symptoms; such individuals would benefit from being removed from the treatment, having the dose reduced, or being "rested" regularly from the treatment. Current medications used to treat chorea are particularly prone to significant side effects. Individuals with mild-to-moderate chorea may be better assisted with nonpharmacologic therapies such as movement training and speech therapy. * Depression. Standard treatment is appropriate when indicated [Paulsen et al 2005b, Phillips et al 2008]. ### Surveillance Regular evaluations should be made to address the appearance and severity of chorea, rigidity, gait problems, depression, behavioral changes, and cognitive decline [Anderson & Marshall 2005, Skirton 2005]. The Behavior Observation Scale Huntington (BOSH) is a scale developed for the rapid and longitudinal assessment of functional abilities of persons with HD in a nursing home environment [Timman et al 2005]. For longitudinal studies, the Unified Huntington's Disease Rating Scale (UHDRS) is used [Huntington Study Group 1996, Siesling et al 1998, Youssov et al 2013]. The total functional capacity (TFC) scale is used to describe the progression of HD, the level of functioning, and requirements for additional caregiver aid (TFC scale). ### Agents/Circumstances to Avoid L-dopa-containing compounds may increase chorea. Alcohol and smoking are discouraged. ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation A wide range of potential therapeutics are under investigation in both animal models of HD and human clinical trials [Wild & Tabrizi 2014]. This diversity reflects the variety of cellular pathways known to be perturbed in HD [Bonelli et al 2004, Rego & de Almeida 2005, Borrell-Pagès et al 2006, Graham et al 2006, Bonelli & Hofmann 2007]. * Pharmacologic agents being investigated include inhibitors of: apoptosis, excitotoxicity, huntingtin aggregation, huntingtin proteolysis, huntingtin phosphorylation, inflammation, oxidative damage, phosphodiesterase activity, histone deacetylase, and transglutaminase activity; as well as compounds that modulate mitochondrial function, chaperone activity, transcription, and neurotrophic support. * Therapeutics that have shown improvements in preclinical animal models of HD and have been advanced to clinical trials include minocycline, sodium butyrate, essential fatty acids, racemide, creatine, cystamine, riluzole, memantine, resveratrol, cannabis extract (THC and CBD), coenzyme Q10, and a phosphodiesterase 10a inhibitor [Bender et al 2005, Puri et al 2005, Bonelli & Wenning 2006, Ondo et al 2007, Okamoto et al 2009, Huntington Study Group DOMINO Investigators 2010, Hersch et al 2017, McGarry et al 2017]. Notably, many of these therapeutic agents have failed to meet clinical endpoints and demonstrate efficacy in modifying clinical progression of HD. Experimental therapeutics including pridopidine, laquinimod, and a semaphorin-4D neutralizing antibody are still in clinical development. * Gene-silencing approaches to target the cause of HD have been shown to be safe and efficacious in preclinical animal studies and are currently undergoing or on the verge of entering clinical trials. These include approaches using RNA interference (RNAi) or antisense oligonucleotides (ASOs) [Boudreau et al 2009, Pfister & Zamore 2009, Hu et al 2010, McBride et al 2011, Kordasiewicz et al 2012, Aronin & DiFiglia 2014, Dufour et al 2014, Stanek et al 2014, Pfister et al 2018]. These approaches either aim to silence all huntingtin expression in a nonselective manner [Boudreau et al 2009, McBride et al 2011, Kordasiewicz et al 2012] or are allele selective for only the mutated HTT allele [Gagnon et al 2010, Carroll et al 2011, Evers et al 2011, Skotte et al 2014, Southwell et al 2014, Datson et al 2017]. Allele selectivity can be achieved by targeting the expanded CAG tract [Gagnon et al 2010, Evers et al 2011, Datson et al 2017] or by targeting polymorphisms in linkage disequilibrium with the CAG expansion [Carroll et al 2011, Skotte et al 2014, Southwell et al 2014, Kay et al 2015, Southwell et al 2018]. Results from the first in-human Phase I/IIa clinical trial evaluating the HTT targeted ASO showed that IONIS-HTTRx (RG6042) was well tolerated at all doses tested and resulted in dose-dependent reductions of mHTT in cerebrospinal fluid (CSF) [Tabrizi et al 2019]. * Cell transplantation studies in HD have shown variable results with small numbers of individuals [Furtado et al 2005, Bachoud-Lévi et al 2006, Farrington et al 2006, Dunnett & Rosser 2007, Barker et al 2013]; however, additional larger studies are under way [Lopez et al 2014]. Moreover, the safety and efficacy of intravenously injected mesenchymal stem cells is currently being tested in a first-in-human clinical trial for individuals with HD (NCT02728115). Of concern, recent studies suggest that mutated huntingtin is capable of spreading into the allografted neural tissue [Cicchetti et al 2014]. Numerous human clinical trials are planned or under way for HD and are listed at huntingtonstudygroup.org. A number of drug trials have been completed and/or are ongoing. Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. ### Other Biomarker studies, such as TRACK-HD, PREDICT-HD, and ENROLL-HD, have been conducted to identify early changes in disease progression using imaging, clinical scales, and physiologic measurements [Scahill et al 2012, Ross et al 2014]. Longitudinal studies of persons at risk for HD have also been performed [Huntington Study Group PHAROS Investigators 2006, Paulsen et al 2006, Tabrizi et al 2012]. A number of candidate molecular biomarkers of disease onset and clinical progression have been assessed in HD patient cohorts, yet only a few have been validated. Mutated huntingtin levels in CSF have been shown to correlate with disease stage in HD [Southwell et al 2015, Wild et al 2015] and potentially reflect levels of mHTT in the brain [Southwell et al 2015]. Therefore, mHTT levels in CSF may provide a reliable biomarker of clinical progression and may provide a proxy measurement for HTT suppression in the brain for HTT-targeted clinical trials. Moreover, levels of neurofilament light chain in blood and CSF have been shown to be a potential prognostic biomarker of disease onset and clinical progression as well as regional brain atrophy in individuals with HD [Byrne et al 2017, Johnson et al 2018]. Children and adolescents living with a parent affected with HD, sometimes in very deprived conditions, can have special problems. Referral to a local HD support group for educational material and needed psychological support is helpful (see Resources). Donepezil, a drug used to treat Alzheimer disease, has not improved motor or cognitive function in HD [Cubo et al 2006]. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Huntington Disease	c0020179	29,829	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1305/	2021-01-18T21:19:28	{"mesh": ["D006816"], "synonyms": ["Huntington Chorea"]}
A rare soft tissue sarcoma characterized by a high-grade lesion occurring almost exclusively in adults, composed of bizarre polygonal, round, and spindle cells with evidence of smooth muscle differentiation. Patients usually present with a rapidly growing, painful mass located in the deep soft tissues of the extremities, but also other anatomic regions. Prognosis is generally poor. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Pleomorphic rhabdomyosarcoma	c0334480	29,830	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=293199	2021-01-23T17:06:14	{"umls": ["C0334480"], "icd-10": ["C49.9"]}
## Clinical Features Xia et al. (2002) described a Chinese family segregating bilateral, postlingual, progressive, and sensorineural nonsyndromic hearing impairment. High-frequency hearing loss began at the second or third decade and progressed to profound deafness involving all frequencies. No patients showed malformations of the inner ear by CT examination or abnormal function by vestibular testing. Mapping In a Chinese pedigree segregating autosomal dominant nonsyndromic hearing loss, Xia et al. (2002) mapped the disorder to chromosome 5q31.1-q32. Fine mapping indicated that the disease gene was located within an 8.8-cM region between markers D5S2056 and D5S638, with a maximum 2-point lod score of 6.89 at D5S2017. No mutations were identified in the POU4F3 (602460) or DIAPH1 (602121) genes, both of which map to 5q31. Molecular Genetics Qiong et al. (2008) sequenced the exons and intron-exon boundaries of 52 candidate genes in the 5q31 region in the patients described by Xia et al. (2002). Qiong et al. (2008) found 108 SNPs; however, none was identified as disease causing. Nomenclature Xia et al. (2002) referred to the deafness locus that they located on 5q as DFNA42; however, the HUGO Nomenclature Committee assigned this deafness locus DFNA52. INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Hearing loss, sensorineural progressive postlingual, high-frequency progressing to all frequencies \- Normal vestibular function MISCELLANEOUS \- Hearing loss progresses to profound deafness \- Age of onset between 20 to 30 years \- One Chinese family with 14 affected individuals has been described (last curated February 2014) ▲ 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, AUTOSOMAL DOMINANT 52	c1843232	29,831	omim	https://www.omim.org/entry/607683	2019-09-22T16:08:48	{"doid": ["0110578"], "mesh": ["C564348"], "omim": ["607683"], "orphanet": ["90635"], "synonyms": ["Autosomal dominant non-syndromic sensorineural hearing loss type DFNA", "Autosomal dominant isolated sensorineural hearing loss type DFNA", "Autosomal dominant non-syndromic neurosensory deafness type DFNA", "Alternative titles", "Autosomal dominant isolated neurosensory deafness type DFNA", "Autosomal dominant isolated neurosensory hearing loss type DFNA", "DEAFNESS, AUTOSOMAL DOMINANT 42", "Autosomal dominant isolated sensorineural deafness type DFNA", "Autosomal dominant non-syndromic neurosensory hearing loss type DFNA"]}
Short ulna-dysmorphism-hypotonia-intellectual disability syndrome is a rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by mild to severe global development delay, severe intellectual disability, mild hypotonia, a short ulna, hirsutism of the face and extremities, minimal scoliosis, and facial dysmorphism, notably a tall broad forehead, synophrys, hypertelorism, malar hypoplasia, broad nose with thick alae nasi, low-set, small ears, long philtrum, thin upper lip and everted lower lip vermilion. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Short ulna-dysmorphism-hypotonia-intellectual disability syndrome	c3554609	29,832	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=357175	2021-01-23T17:07:07	{"omim": ["615162"], "icd-10": ["Q87.8"]}
A number sign (#) is used with this entry because of evidence that epidermolysis bullosa simplex with pyloric atresia (EBSPA) is caused by homozygous or compound heterozygous mutation in the gene encoding plectin-1 (PLEC1; 601282) on chromosome 8q24. EBS with muscular dystrophy (EBSMD; 226670), EBS Ogna type (EBSOG; 131950), and EBS with nail dystrophy (EBSND; 616487) are allelic disorders. See also junctional EB with pyloric atresia (JEBPA), a similar disorder caused by mutation in the ITGB4 (147557) or the ITGA6 (147556) gene. Description EBSPA is an autosomal recessive genodermatosis characterized by severe skin blistering at birth and congenital pyloric atresia. Death usually occurs in infancy. In reports of 2 consensus meetings for EB, Fine et al. (2000, 2008) considered EBSPA to be a 'basal' form of simplex EB because the electron microscopy shows that skin cleavage occurs in the lower basal level of the keratinocyte, just above the hemidesmosome. There is often decreased integration of keratin filaments with hemidesmosomes. Clinical Features Cowton et al. (1982) reported a female infant born with epidermolysis bullosa, aplasia cutis, and pyloric atresia. The mother had increased alpha-fetoprotein during early pregnancy. Electron microscopy of skin biopsies showed EB simplex. Morrell et al. (2000) reported a male infant, born of consanguineous parents, with numerous and skin erosions and bullae at birth. There was extensive absence of skin on the face, trunk, and limbs. Other anomalies included malformed pinnae fused to the scalp, hypoplastic nasal alae, and joint contractures. The pregnancy was complicated by polyhydramnios. Electron microscopy of skin biopsies showed cleavage in the lowermost third of basal keratinocytes, consistent with a diagnosis of EBS. Abdominal radiographs and clinical symptoms indicated pyloric atresia, which was surgically repaired. He died at age 5 weeks of respiratory failure. Genetic analysis excluded mutations in the ITGB4 and ITGA6 genes. Charlesworth et al. (2003) reported 3 sisters, born of consanguineous Turkish parents, with features consistent with EBSPA. Clinical features included congenital absence of the skin on the nose, skin fragility with blister formation, and dysmorphic features, including deep-set eyes, hypoplastic ears with helices fused to the skull, hypoplastic nose, and joint contractures. The pregnancies were complicated by polyhydramnios, and ultrasonographic findings suggested pyloric atresia. However, due to the religious beliefs of the family, postmortem examination and extensive studies were refused. All the girls died within hours of birth or termination. Available skin biopsies of 2 of the patients were consistent with EBS with cleavage in the lower part of basal keratinocytes. Nakamura et al. (2005) reported 3 patients from 2 unrelated families with EBSPA. In the first family, 2 brothers were born with multiple blisters and ulcers on all areas of the body. Pyloric atresia was apparent by ultrasound during the pregnancies. Both died at ages 16 and 4 months, respectively. The proband in the second family had a similar disease course. Electron microscopy in all patients showed cleavage at the base of the basal keratinocytes and hypoplastic hemidesmosomes. Immunohistochemical studies showed decreased or absent expression of PLEC1. Pfendner and Uitto (2005) reported 4 consanguineous families in which at least 1 member had EBSPA. All patients had extensive blistering at birth with pyloric atresia, most had aplasia cutis, and all died from complications of the disorder shortly after birth. Molecular analysis confirmed homozygous mutations in the PLEC1 gene (see, e.g., 601282.0007 and 601282.0009). Pfendner and Uitto (2005) noted that 1 of the mutations deleted a region that may be important for plectin interaction with alpha-6/beta-4 integrin, and that mutations in the latter genes result in the phenotypically similar JEB-PA. Thus, PA in all of these patients is likely related to perturbed interactions between plectin and alpha-6/beta-4 integrin within attachment structures expressed during gastrointestinal development. Molecular Genetics In 3 Turkish female infants with lethal EBSPA, Charlesworth et al. (2003) identified a homozygous mutation in the PLEC1 gene (601282.0006). In 2 unrelated patients with lethal EBSPA, Nakamura et al. (2005) identified compound heterozygous mutations in the PLEC1 gene (see, e.g., 601282.0007; 601282.0008). INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Malformed pinnae \- Hypoplastic ears fused to the scalp Eyes \- Deep-set eyes Nose \- Hypoplastic nasal alae ABDOMEN Gastrointestinal \- Pyloric atresia SKELETAL \- Joint contractures SKIN, NAILS, & HAIR Skin \- Epidermolysis bullosa simplex \- Blistering, generalized \- Congenital absence of skin in some areas (aplasia cutis) \- Extreme skin fragility Electron Microscopy \- Cleavage occurs within the lower part of basal keratinocytes \- Hemidesmosomes may be disrupted \- Absence of plectin-1 immunostaining PRENATAL MANIFESTATIONS Amniotic Fluid \- Polyhydramnios LABORATORY ABNORMALITIES \- Increased alpha-fetoprotein in the mother during early pregnancy while carrying an affected fetus MISCELLANEOUS \- Onset in utero \- Death usually in infancy \- See also junctional EB with pyloric atresia ( 226730 ) MOLECULAR BASIS \- Caused by mutation in the plectin 1 gene (PLEC1, {601282.0006)} ▲ 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	EPIDERMOLYSIS BULLOSA SIMPLEX WITH PYLORIC ATRESIA	c2677349	29,833	omim	https://www.omim.org/entry/612138	2019-09-22T16:02:17	{"mesh": ["C567408"], "omim": ["612138"], "orphanet": ["158684"], "synonyms": ["Alternative titles", "EBS WITH PYLORIC ATRESIA"]}
A number sign (#) is used with this entry because of evidence that familial focal epilepsy with variable foci-4 (FFEVF4) is caused by heterozygous mutation in the SCN3A gene (182391) on chromosome 2q24. Heterozygous mutation in the SCN3A gene can also cause EIEE62 (617938), a more severe epileptic disorder. Description FFEVF4 is an autosomal dominant seizure disorder characterized by onset of focal seizures in the first years of life. Some patients may have secondary generalization and/or mild developmental deficits (summary by Vanoye et al., 2014). For a discussion of genetic heterogeneity of FFEVF, see FFEVF1 (604364). Clinical Features Vanoye et al. (2014) reported 4 unrelated children with early-onset focal seizures. One patient had onset of seizures in the neonatal period, 2 had onset between 16 and 22 months, and the fourth patient had onset at age 5 years. The seizures were well controlled, and all were able to discontinue medication later in childhood. Two patients had mild cognitive impairment, including speech delay, attention deficit-hyperactivity, and learning disabilities, but the other 2 patients had normal development. Brain imaging was normal in 2 patients and showed nonspecific minor abnormalities in the other 2 patients. Three patients had a family history of epilepsy, but affected family members were not available for study. Lamar et al. (2017) reported a 2-year-old girl with global developmental delay, hypotonia, microcephaly, and onset of focal seizures in the first week of life. She also had autonomic dysfunction, including skin flushing and sweating associated with pupil dilation and ptosis. She was unable to walk, had delayed speech, and poor overall growth. Cytogenetics Celle et al. (2013) reported a 3-year-old boy with delayed psychomotor development, autistic features, severe language delay, and microcephaly associated with a 291-kb interstitial deletion at chromosome 2q24.3 including both the SCN2A (182390) and SCN3A genes. The patient did not have seizures. Parental DNA was not available for study. Molecular Genetics In 4 unrelated patients with FFEVF4, Vanoye et al. (2014) identified 4 different heterozygous missense mutations in the SCN3A gene (see, e.g., 182391.0001-182391.0003). The mutations were found by genetic screening of the SCN3A gene in 179 pediatric patients with focal epilepsy who were negative for mutations in the SCN1A gene. No family members were available for study, so analysis of inheritance pattern and/or segregation was not possible. In vitro functional expression studies showed that the mutations caused variable defects of channel function, with only some of the mutations altering the activation and/or inactivation kinetics. However, all the mutations resulted in increased inward currents during a slow depolarizing voltage ramp, indicating channel dysfunction capable of enhancing the response to subthreshold depolarizing inputs and promoting hyperexcitable networks. Zaman et al. (2018) noted that all the variants identified by Vanoye et al. (2014) were found at a low frequency in the ExAC database and may either result in subtle changes in channel function or may act as risk alleles. In an 2-year-old girl with FFEVF4, Lamar et al. (2017) identified a de novo heterozygous missense mutation in the SCN3A gene (L247P; 182391.0004). The mutation was found by exome sequencing and confirmed by Sanger sequencing. In vitro functional expression studies showed that the mutant channel had no detectable sodium current resulting from a significant reduction of mutant SCN3A at the cell surface, suggesting that the mutation caused a trafficking defect. Fewer channels at the cell surface would be predicted to reduce the magnitude of the inward current, which may contribute to disease pathogenesis. The findings were consistent with a loss-of-function effect. Animal Model Lamar et al. (2017) found that heterozygous Scn3a +/- mice had decreased Scn3a mRNA and protein levels in the brain compared to wildtype. Mutant mice had increased susceptibility to induced seizures, but did not exhibit spontaneous seizures. Heterozygous mice also showed deficits in locomotor activity and motor learning. Some of the mutant mice showed focal cortical abnormalities, including disruptions in cortical lamination and invaginations. INHERITANCE \- Autosomal dominant GROWTH Other \- Poor overall growth (patient A) HEAD & NECK Head \- Microcephaly (patient A) NEUROLOGIC Central Nervous System \- Seizures, focal, well-controlled \- Delayed psychomotor development, mild (in some patients) \- Learning disabilities (in some patients) \- Speech delay (in some patients) \- Autonomic dysfunction (patient A) MISCELLANEOUS \- Onset in first years of life \- Seizures are controlled by medication \- Seizures may remit later in childhood MOLECULAR BASIS \- Caused by mutation in the voltage-gated sodium channel, type III, alpha subunit gene (SCN3A, 182391.0001 ) ▲ 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, FAMILIAL FOCAL, WITH VARIABLE FOCI 4	c4693694	29,834	omim	https://www.omim.org/entry/617935	2019-09-22T15:44:19	{"omim": ["617935"]}
## Summary ### Clinical characteristics. AIP familial isolated pituitary adenoma (AIP-FIPA) is defined as the presence of an AIP germline pathogenic variant in an individual with a pituitary adenoma (regardless of family history). The most commonly occurring pituitary adenomas in this disorder are growth hormone-secreting adenomas (somatotropinoma), followed by prolactin-secreting adenomas (prolactinoma), growth hormone and prolactin co-secreting adenomas (somatomammotropinoma), and nonfunctioning pituitary adenomas (NFPA). Rarely TSH-secreting adenomas (thyrotropinomas) are observed. Clinical findings result from excess hormone secretion, lack of hormone secretion, and/or mass effects (e.g., headaches, visual field loss). Within the same family, pituitary adenomas can be of the same or different type. Age of onset in AIP-FIPA is usually in the second or third decade. ### Diagnosis/testing. The diagnosis of AIP-FIPA is established in a proband with a pituitary adenoma by identification of a heterozygous germline pathogenic variant in AIP by molecular genetic testing. ### Management. Treatment of manifestations: Pituitary adenomas identified in those with AIP-FIPA are generally treated in the same manner as pituitary adenomas of unknown cause: they can be treated by medical therapy (somatostatin analogs, growth hormone receptor antagonists, and dopamine agonists), surgery, and/or radiotherapy. Although surgery is usually performed in persons with AIP-FIPA, it often does not fully control the tumor; thus, medical therapy and radiotherapy following surgery may be required to control hormone output and tumor growth. AIP-FIPA adenomas often do not respond well to first-generation somatostatin analog, while data suggest that they may respond better to second-generation multi-ligand agonists. Prolactinomas are treated with dopamine agonist therapy or surgery and can be aggressive and difficult to treat. NFPA is treated with surgery and if necessary radiotherapy. Prevention of secondary complications: Expert management for hypopituitarism which can be due to tumor size, surgery, or radiotherapy. Persons on glucocorticoid replacement therapy need to increase their steroid dose when ill or stressed. Surveillance: In asymptomatic individuals: annual growth assessment and evaluation for signs/symptoms of pituitary adenoma and pubertal development from age four years until adulthood. Continue annual evaluation for signs and symptoms of pituitary adenoma until age 30 years and then every five years between ages 30 and 50 years. Annual pituitary function tests (serum IGF-1, prolactin, estradiol/testosterone, LH, FSH, TSH, free T4) beginning at age four years until age 30; pituitary MRI at age ten years and repeated (every 5 years has been suggested) or as necessary based on clinical and biochemical parameters until age 30 years. Starting at age 30 to 50 years surveillance can be relaxed. In symptomatic individuals: annual clinical assessment and pituitary function tests (serum IGF-1, spot growth hormone, prolactin, estradiol/testosterone, LH, FSH, TSH, free T4, and morning cortisol); if indicated annual dynamic testing to evaluate for hormone excess or deficiency (e.g., glucose tolerance test, insulin tolerance test); pituitary MRI with frequency depending on clinical status, previous extent of the tumor, and treatment modality. Clinical monitoring of secondary complications of the tumor and/or its treatment (e.g., diabetes mellitus, hypertension, osteoarthritis, hypogonadism, osteoporosis); in those with acromegaly, colonoscopy at age 40 years and repeated every three to ten years depending on the number of colorectal lesions and IGF-1 levels. Evaluation of relatives at risk: Family members at risk for AIP-FIPA warrant molecular genetic testing for the family-specific pathogenic variant to identify those who harbor the variant and thus require surveillance for pituitary adenomas. ### Genetic counseling. AIP-FIPA is inherited in an autosomal dominant manner. Each child of an individual with AIP-FIPA has a 50% chance of inheriting the pathogenic variant. Prenatal testing for pregnancies at increased risk is possible if the AIP pathogenic variant of an affected family member has been identified; however, because AIP-FIPA demonstrates reduced penetrance, the finding of an AIP pathogenic variant prenatally does not allow accurate prediction of whether a tumor will develop, or the type of adenoma, age of onset, prognosis, or availability and/or outcome of treatment. ## Diagnosis ### Suggestive Findings AIP familial isolated pituitary adenoma (AIP-FIPA) should be suspected in individuals with the following: * A pituitary adenoma diagnosed before age 18 years, especially a growth hormone-secreting pituitary adenoma, regardless of family history * A pituitary macroadenoma (tumor >10 mm in diameter) diagnosed before age 30 years, especially a growth hormone-secreting pituitary adenoma, regardless of family history * A prolactin-secreting pituitary macroadenoma (tumor >10 mm in diameter) diagnosed before age 30 years, regardless of family history Note: (1) A germline AIP pathogenic variant is identified in approximately 20% of simplex cases of childhood-onset growth hormone-secreting pituitary adenomas [Chahal et al 2010, Cazabat et al 2011, Tichomirowa et al 2011]. (2) A germline AIP pathogenic variant is identified in 11% of simplex cases of young-onset (age <30 years) pituitary macroadenomas [Tichomirowa et al 2011]. * A family history of more than one individual with a pituitary adenoma Note: (1) A germline AIP pathogenic variant is identified in approximately 20% of families with FIPA [Chahal et al 2010] and in 40% of families in which somatotropinomas are the only tumor type observed. (2) To date, AIP pathogenic variants have not been identified in families with two adults with microprolactinomas (prolactin secreting tumors <10 mm in diameter); therefore, the probability of identifying an AIP pathogenic variant in such a family is low. * Absence of clinical features of other disorders associated with pituitary adenomas such as multiple endocrine neoplasia type 1 or type 4 (MEN1 or MEN4) or Carney complex The pituitary adenomas in individuals with AIP-FIPA can include: * Growth hormone-secreting (somatotropinoma) Note: Somatotroph (growth hormone-secreting) cell hyperplasia has also been described in individuals with AIP-FIPA, although it is extremely rare. * Prolactin-secreting (prolactinoma) * Growth hormone and prolactin co-secreting (somatomammotropinoma) * Nonfunctioning pituitary adenoma (NFPA) Note: Most AIP-related NFPAs show growth hormone and/or prolactin immunostaining in tumor tissue. * Thyrotropinoma (TSH-secreting) (rare; 1 thyrotropinoma described) * Multihormonal (i.e., secreting >1 pituitary hormone) (extremely rare apart from tumors secreting growth hormone and prolactin) No unequivocal cases of corticotropinomas have been described. ### Establishing the Diagnosis The diagnosis of AIP-FIPA is established in a proband with a pituitary adenoma(s) by identification of a heterozygous germline pathogenic variant in AIP by molecular genetic testing (see Table 1). Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing and 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 phenotype of AIP-FIPA can occur with other disorders, individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those with a phenotype indistinguishable from other inherited disorders with pituitary tumors 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 AIP-FIPA, molecular genetic testing approaches can include single-gene testing (or concurrent or serial single-gene testing) or use of a multigene panel: * Single-gene testing. Sequence analysis of AIP detects small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. Perform sequence analysis first. If no pathogenic variant is found perform gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications. * A multigene panel that includes AIP 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 other inherited disorders characterized by pituitary tumors, comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is a possible option. Exome sequencing is most commonly used; genome sequencing is also possible. If exome sequencing is not diagnostic – and particularly when evidence supports autosomal dominant inheritance – 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 AIP-FIPA View in own window Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method AIPSequence analysis 3~95% 4, 5 Gene-targeted deletion/duplication analysis 6~5% 7 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on allelic variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. 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\. Georgitsi et al [2008]; Igreja et al [2010]; Hernández-Ramírez et al [2015]; Author, personal observation 5\. One promoter variant has been reported (see Molecular Genetics). 6\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 7\. To date, four individuals/families with exon or multiexon deletions and two families with whole-gene deletions have been identified [Georgitsi et al 2008, Igreja et al 2010, Hernández-Ramírez et al 2015, Marques et al 2020]. ## Clinical Characteristics ### Clinical Description To date, more than 300 individuals with a germline pathogenic variant in AIP have been identified [Beckers et al 2013, Hernández-Ramírez et al 2015]. The following description of the phenotypic features associated with this condition is based on these reports. ### Table 2. Pituitary Adenomas in Individuals with AIP-FIPA View in own window Type of Pituitary Adenoma% of Persons w/Type of AdenomaReference Somatotropinoma (growth hormone-secreting)70%Hernández-Ramírez et al [2015] Somatomammotropinoma (growth hormone- and prolactin-secreting)10% Prolactinoma10% Nonfunctioning pituitary adenoma8% Thyrotropinoma (TSH-secreting)Rare The median age of diagnosis of AIP familial isolated pituitary adenoma (AIP-FIPA) is 23 years. The earliest age of diagnosis of a pituitary adenoma in a person with an AIP pathogenic variant is four years [Dutta et al 2019]. #### Hormone Dysfunction Somatotropinoma (growth hormone-secreting pituitary adenoma) * Acromegaly. Approximately 80% of persons with AIP-FIPA have acromegaly. Persons with acromegaly have excess growth hormone secretion resulting in enlargement of hands and feet, and coarse facial appearance with prognathism and malocclusion of teeth. They may have headaches, joint pain, carpal tunnel syndrome, sleeping difficulties, excessive sweating, hypertension, diabetes mellitus, and muscle weakness. Individuals with longstanding acromegaly often have cardiovascular and rheumatologic/orthopedic complications, which need to be treated accordingly. Individuals with acromegaly of any cause are at increased risk for colon cancer. If acromegaly starts in childhood/adolescence it can lead to pituitary gigantism. * Pituitary gigantism. Excessive growth hormone secretion before fusion of the growth plates results in pituitary gigantism. Exceptionally tall stature results from a combination of high growth hormone levels and delayed onset of puberty due to suppression of LH/FSH secretion by mass effect of the tumor and/or, when present, the direct effect of high prolactin levels. One third of all individuals with a germline AIP pathogenic variant and 40%-50% of individuals with AIP-FIPA with a somatotropinoma have pituitary gigantism [Daly et al 2010]. Prolactinomas. Approximately 10% of persons with an AIP pathogenic variant have a prolactinoma [Daly et al 2010, Igreja et al 2010]. Prolactinomas result in signs and symptoms of prolactin excess (i.e., amenorrhea, sexual problems, galactorrhea, and infertility) and can also cause mass effects (e.g., visual field defects, headaches). Almost all AIP-related prolactinomas are macroadenomas with male predominance [Daly et al 2010, Igreja et al 2010]. Nonfunctioning pituitary adenomas (NFPAs). NFPAs are seen in 4%-7% of persons with an AIP pathogenic variant. NFPAs are usually diagnosed due to the local effects of the tumor, such as bitemporal hemianopia or hypogonadism. It is unclear why these silent adenomas do not release hormones at a clinically recognizable level; however, there is likely to be a continuum between fully functional and completely silent adenomas [Drummond et al 2019]. Distinguishing NFPA from prolactinomas can occasionally be difficult due to the stalk effect (pituitary stalk compression resulting in increased prolactin levels in the absence of a prolactin-secreting adenoma). In AIP-FIPA, NFPAs that have been resected are often (but not always) silent somatotropinoma or lactotroph adenomas [Igreja et al 2010, Villa et al 2011]. In families with AIP-FIPA, NFPAs are identified at a younger age than NFPAs in persons without a germline pathogenic variant [Daly et al 2010]. Screening of clinically unaffected AIP heterozygotes can identify small nonfunctioning pituitary lesions, equivalent to incidentalomas in the general population [Caimari et al 2018]. Thyrotropinomas (TSH-secreting adenomas causing hyperthyroidism) are rarely seen in AIP-FIPA. A single individual with AIP-FIPA and a thyrotropinoma has been described [Daly et al 2007]. AIP-FIPA does not appear to increase the risk of corticotropinoma. The individuals with FIPA previously reported with Cushing disease were subsequently found to have likely benign variants in AIP, variants of uncertain significance [Beckers et al 2013], or no loss of heterozygosity identified in the tumor [Cazabat et al 2012]. Subfertility is common in persons with pituitary tumors. No data are available specifically regarding subfertility in AIP-FIPA. Mass effects. Large pituitary adenomas can be associated with deficiencies of other pituitary hormones that result in subfertility, hypothyroidism, hypoadrenalism, low levels of growth hormone, and panhypopituitarism. Macroadenomas (>10 mm in diameter) may also press on the optic chiasm and optic tracts, causing bitemporal hemianopia. The tumor may invade the adjacent cavernous sinus. Headache can be present in any type of adenoma but is especially common in acromegaly; the mechanism for the increased frequency is unknown. Larger pituitary tumors may autoinfarct, resulting in pituitary apoplexy (sudden-onset severe headache, visual disturbance, cranial nerve palsies, hypoglycemia, and hypotensive shock). Pituitary apoplexy has been described in individuals with AIP-FIPA [Chahal et al 2011]. Pituitary carcinoma. To date pituitary carcinoma has not been described in an individual with AIP-FIPA. Other, non-pituitary tumors have been observed in some families with AIP-FIPA; however, because the background population risk for tumors is fairly high and because no consistent pattern has been observed, at present there is no conclusive evidence that an AIP germline pathogenic variant increases the risk for any other tumors. In addition, non-pituitary tumors from AIP heterozygotes have been analyzed for loss of heterozygosity at the AIP locus, and no abnormality was found [Hernández-Ramírez et al 2015]. ### Genotype-Phenotype Correlations Individuals with AIP truncating pathogenic variants may have a slightly earlier age of onset and diagnosis compared to those with non-truncating pathogenic variants [Hernández-Ramírez et al 2015]. ### Penetrance Studies on large families with AIP pathogenic variants show a clinical penetrance of pituitary adenomas of approximately 23% (range 15%-30%) [Vierimaa et al 2006, Naves et al 2007, Williams et al 2014, Hernández-Ramírez et al 2015]. Although some families with AIP-FIPA can show high penetrance, the higher levels of penetrance initially reported in some families is probably ascertainment bias due to insufficient information on all at-risk family members (e.g., lack of medical records, information on pituitary hormone testing, and/or imaging studies) [Daly et al 2007, Leontiou et al 2008]. The factors influencing penetrance are not known; the possibility of a second locus has been investigated but not confirmed [Khoo et al 2009, Hernández-Ramírez et al 2015]. ### Nomenclature Previously, pituitary adenoma predisposition (PAP) syndrome was used to refer to individuals who had an AIP pathogenic variant; the term is not used widely. ### Prevalence The exact prevalence of AIP-FIPA is not known. To date, about 150 families and about 150 simplex cases (i.e., a single occurrence in a family) of AIP-FIPA have been identified [Daly et al 2010, Hernández-Ramírez et al 2015, Caimari et al 2018]. ## Differential Diagnosis In children more often than in adults, pituitary adenomas may be a manifestation of a genetic condition. Pituitary adenomas of genetic origin can be divided into isolated and syndromic categories. ### Familial Isolated Pituitary Adenomas (FIPA) FIPA is defined as a hereditary condition associated with pituitary adenomas and no other features of a syndrome known to be associated with pituitary adenomas. X-linked acrogigantism (XLAG), a second genetically characterized type of FIPA, is caused by duplication of GPR101. XLAG, a highly penetrant disorder, is associated with pituitary hyperplasia or adenoma resulting in growth hormone excess with onset in infancy, usually with associated hyperprolactinemia [Trivellin et al 2014]. Most individuals with XLAG have a de novo somatic mosaic genetic alteration not inherited from a parent. Families with FIPA of known or unknown cause can have homogeneous pituitary adenoma phenotypes (i.e., pituitary tumors of the same type) or heterogeneous phenotypes (i.e., pituitary tumors of different types). Aspects of FIPA that tend to differ between families in which a germline AIP pathogenic variant has been identified and those in which no germline AIP pathogenic variant has been identified include: age of onset, number of persons affected in the family, male-to-female ratio, and typical adenoma types. Tumor variables may also include: size, aggressiveness, and response to treatment [Hernández-Ramírez et al 2015] (see Table 3). ### Table 3. Comparison of Findings in Persons with Isolated Pituitary Adenomas by Family History and Presence/Absence of a Germline AIP Pathogenic Variant View in own window CharacteristicsFamilial Isolated Pituitary AdenomaSimplex Somatotropinoma 1 AIP-FIPAXLAGFIPA of unknown cause Clinical featuresAge of onset 24-24 yrsInfancy / early childhood40 yrs43 yrs Average # of affected family members 33-412-3n/a Male-to-female ratio 41:1 to 2:11:21:11:1 Adenoma featuresSomatotropinomas / somatomammotropinomas70%-80%~100%~50%n/a SizeMacroadenomas in vast majorityPituitary hyperplasia-macroadenomaMajority macroadenoma 5Smaller AggressivenessMoreVariableMoreLess Response to treatmentPoorerPoorerPoorerBetter FIPA = familial isolated pituitary adenoma 1\. Simplex case = a single occurrence in a family 2\. Daly et al [2010], Igreja et al [2010], Hernández-Ramírez et al [2015], Daly et al [2016] 3\. Igreja et al [2010] 4\. Cazabat et al [2009], Daly et al [2010], Igreja et al [2010] 5\. Marques et al [2020] ### Syndromes Associated with Pituitary Tumors ### Table 4. Syndromes Associated with Pituitary Tumors View in own window Gene(s)DisorderMOIPituitary Tumor FeaturesOther Features MEN1Multiple endocrine neoplasia type 1 (MEN1)ADPituitary tumors occur in ~40% of affected individuals, most often prolactinomas * Gastro-entero-pancreatic tract tumors * Parathyroid adenoma w/hypercalcemia * Other manifestations CDKN1A CDKN1B CDKN2B CDKN2CMEN1-like syndrome 1ADPituitary tumors occur in ~40% of affected individuals, most often somatotropinomas * Rare disorder * Clinical findings similar to those of MEN1 PRKAR1A PRKACB 2Carney complexAD~80% of affected individuals have somatotroph cell hyperplasia or small pituitary adenoma * Skin pigmentary abnormalities * Myxomas of the organs * Schwannomas * Primary pigmented nodular adrenocortical disease * Large-cell calcifying Sertoli cell tumors * Thyroid nodules * Acromegaly GNASMcCune-Albright syndromen/a (somatic) * ~30% of affected individuals have pituitary disease * Pituitary adenomas w/↑ secretion of growth hormone * Hyperplasia of somatomammotroph cells w/prolactinemia * Polyostotic fibrous dysplasia * Café au lait patches * Multiple endocrine disorders (e.g., multinodular goiters, multinodular adrenal hyperplasia, & precocious puberty) MAX SDHA SDHB SDHC SDHD RETHereditary paraganglioma-pheochromocytoma syndromesAD * Low penetrance of pituitary disease * Pituitary carcinoma described, vacuolated histology picture * Paragangliomas * Pheochromocytoma * GIST * Kidney tumors DICER1DICER1 syndromeAD * Low penetrance of pituitary disease * ACTH-secreting pituitary blastoma Manifests before age 2 yrs MSH2 MSH6 MLH1 ?PMS2Lynch syndromeAD * Low penetrance of pituitary disease * ACTH-secreting macroadenomas Colorectal, endometrial, ovarian, & other carcinomas USP8Pituitary adenoma 4 (OMIM 219090)AD1 individual w/pituitary adenomaDevelopmental delay AD = autosomal dominant; GIST = gastrointestinal stromal tumor; MEN1 = multiple endocrine neoplasia type 1; MOI = mode of inheritance 1\. Agarwal et al [2009] 2\. One individual with Carney complex (<1% of families with Carney complex) had a germline rearrangement resulting in four copies of PRKACB [Forlino et al 2014]. PRKACB encodes the catalytic subunit Cβ of the cyclic AMP-dependent protein kinase A (PKA). Levels of Cβ and PKA activity were increased in the individual's lymphoblasts and fibroblasts; the authors propose that this is a Carney complex-causing gain-of-function variant. Note: Autopsy and radiologic studies suggest that 14%-22% of the population may harbor a pituitary adenoma, most of these being asymptomatic [Ezzat et al 2004]. Thus, it is possible for two pituitary adenomas, especially prolactinomas, to occur sporadically in a family by chance. ### Other Space-Occupying Lesions In addition to pituitary adenomas, numerous space-occupying lesions can occur in the pituitary fossa [Saeger et al 2007]. The most common space-occupying lesions after pituitary adenomas are craniopharyngiomas, which cause symptoms by compressing the normal pituitary, resulting in hormonal deficiencies and mass effects on the surrounding tissues and brain [Zacharia et al 2012]. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs of an individual with AIP familial isolated pituitary adenoma (AIP-FIPA), the evaluations in Table 5 are recommended (for details see Katznelson et al [2011]). ### Table 5. Recommended Evaluations Following Initial Diagnosis in Individuals with AIP-FIPA View in own window System/ConcernEvaluationComment Pituitary adenoma * LH, FSH, testosterone/estradiol * Visual field evaluation * Consultation w/endocrinologist * If adenoma suspected: pituitary MRI to detect size & extent * DEXA scan in those w/hypogonadism Somatotropinoma (growth hormone- secreting) * Evaluate for signs/symptoms (e.g., stature, change in facial appearance, change in shoe size, problems w/ring sizes, headache, excessive sweating, joint pains, carpal tunnel syndrome). * Spot serum growth hormone, IGF-1 Include: * Review of serial photographs for acromegalic changes; * Measurement of parental heights; * GTT in persons w/findings of acromegaly * Assess ACTH reserve if needed. Prolactinoma * Evaluate for signs/symptoms (e.g., menstrual history, galactorrhea, infertility, low libido, impotence). * Serum prolactin Note: (1) High prolactin levels can be due to stalk effect; (2) There are many non-pituitary causes of hyperprolactinemia. NFPAsEvaluate for signs/symptoms (e.g., headache, lack of other pituitary hormones, visual field problems).Many nonfunctioning adenomas are identified incidentally w/no clinical or biochemical associations. ThyrotropinomaTSH, free T4Consider other causes of thyroid hormone resistance. OtherConsultation w/clinical geneticist &/or genetic counselor GTT = glucose tolerance test; NFPAs = nonfunctioning pituitary adenomas ### Treatment of Manifestations While there is experience with treating pituitary adenomas in symptomatic persons with FIPA, the experience of management and treatment of persons identified prospectively through clinical screening due to family history of FIPA and/or presence of a heterozygous germline AIP pathogenic variant is relatively recent. However, the age of detection in the AIP-FIPA is earlier and the prognosis generally better. Given the prevalence of incidental pituitary adenomas, it is important to remember that such a tumor may arise in an individual with an AIP pathogenic variant, completely by chance. The following recommendations are based on those of Katznelson et al [2011], Melmed et al [2011], Williams et al [2014], and Hernández-Ramírez et al [2015]. ### Table 6. Treatment of Manifestations in Individuals with AIP-FIPA View in own window Manifestation/ConcernTreatmentConsiderations/Other Pituitary microadenomasMedical therapy (e.g., somatostatin analogs, growth hormone receptor antagonists, & dopamine agonists), surgery &/or radiotherapyMonitor microadenomas w/normal clinical & biochemistry findings closely. Pituitary macroadenomasTranssphenoidal surgery, medical therapy, &/or radiotherapySurgery often does not fully control the tumor; large recurring tumors may require radiotherapy if tumor invades neighboring anatomic structures (e.g., cavernous sinus). Somatotropinomas * Radiotherapy (conventional or radiosurgery) for growing adenomas, for which repeat surgery is unlikely to control hormone levels * Standard treatment of cardiovascular & rheumatologic/orthopedic complications for those w/acromegaly Tumors often do not respond to medical therapy w/1st-generation somatostatin analogs; 1 2nd-generation may have more effect. 2 Prolactinomas * Dopamine agonist therapy (e.g., cabergoline) * Surgical treatment often used for macroprolactinoma (diameter >10 mm) Prolactinomas in AIP-FIPA can be aggressive & difficult to treat. 1 Nonfunctioning pituitary adenomasSurgery & (if necessary) radiotherapyUsually do not respond to traditional somatostatin analogs 1\. Daly et al [2010] 2\. Daly et al [2019] ### Prevention of Secondary Complications Tumor size, surgery, and/or radiotherapy can cause hypopituitarism, which requires careful expert follow up. Persons on glucocorticoid replacement therapy need to increase their steroid dose when ill or stressed. ### Surveillance No formal guidelines regarding surveillance of persons with AIP-FIPA have been established. The following recommendations are based on expert opinion from the literature and on the authors' personal experience with more than 200 persons with symptomatic or asymptomatic AIP-FIPA. ### Table 7. Recommended Surveillance for Individuals with AIP-FIPA View in own window System/ConcernEvaluationFrequency Pituitary adenoma * Measure height & weight; calculate height velocity * Evaluate for signs/symptoms & evaluate pubertal development Annually beginning at age 4 yrs until adulthood 1 Evaluate for signs/symptoms.Annually until age 30 yrs & every 5 yrs between ages 30 & 50 yrs, earlier if symptomatic Serum IGF-1, prolactin, estradiol/testosterone, LH, FSH, TSH, free T4Annually from age 4 yrs to 30 yrs; to date, no secreting pituitary adenomas have developed after age 30 in those w/normal findings at age 30 yrs. Blood tests if symptomatic after age 30 yrs. Pituitary MRI * Baseline at age 10 yrs unless indicated earlier due to clinical findings * Repeat MRI every 5 yrs until age 30 yrs (if clinical & pituitary function tests remain normal) * If clinical or biochemical abnormality between ages 30 & 50 yrs 1\. In children between ages four and ten years, it may be difficult to get annual blood samples. In these cases, monitoring symptoms and growth may be an acceptable alternative, as non-growth hormone-secreting adenomas before age ten years are rare. ### Table 8. Recommended Additional Surveillance for Symptomatic Individuals with AIP-FIPA View in own window System/ConcernEvaluationFrequency History of pituitary adenoma * Clinical assessment * Serum IGF-1, spot growth hormone, prolactin, estradiol/testosterone, LH, FSH, TSH, free T4, morning cortisol * If necessary dynamic testing (e.g., glucose tolerance test, insulin tolerance test) to evaluate for hormone excess or deficiency Annually Pituitary MRIFrequency depends on clinical status, previous extent of tumor, & treatment modality. Osteoporosis in those w/hypogonadismDEXA evaluationPer established guidelines Complications of acromegalyMonitor for diabetes mellitus, hypertension, hypogonadism, & osteoarthritis.Per established guidelines Colonoscopy * At age 40 yrs * Repeat every 3 to 10 yrs depending on # of colorectal lesions on initial colonoscopy & IGF-1 levels. 1 1\. Cairns et al [2010] ### Evaluation of Relatives at Risk It is appropriate to clarify the genetic status of apparently asymptomatic at-risk relatives of an affected individual by molecular genetic testing for the familial AIP pathogenic variant so that morbidity and mortality can be reduced by early diagnosis and treatment. Identification of at-risk family members may also reduce the need for costly screening procedures in those family members who have not inherited a pathogenic variant. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management Pregnancy may increase the size of a growth hormone-secreting adenoma or a prolactin-secreting adenoma (especially macroadenomas); thus, a pregnant woman with pituitary macroadenoma is at risk of developing visual field defects. In each trimester it is appropriate to inquire about headaches and perform visual field testing. Medical therapies are stopped during pregnancy. See MotherToBaby for further information on medication use during pregnancy. ### Therapies Under Investigation A study that is actively ascertaining individuals with FIPA or childhood-onset pituitary adenoma is listed in ClinicalTrials.gov. Growth hormone receptor antagonists block the action of endogenous growth hormone, thereby controlling disease manifestations such as headaches, soft tissue enlargement, diabetes mellitus, hypertension, and high IGF-1 levels. A growth hormone receptor antagonist has been used successfully in persons with AIP-FIPA and acromegaly and pituitary gigantism [Goldenberg et al 2008]. In two individuals with AIP-related pituitary tumors resistant to treatment with first-generation somatostatin analogs, pasireotide, a second-generation multi-ligand somatostatin analog with affinity to multiple somatostatin receptors, was shown to achieve long-term control of disease [Daly et al 2019]. Although growth hormone receptor antagonists are currently not licensed for pediatric use, several case reports have shown their effectiveness, especially when IGF-1 levels need to be reduced immediately to prevent abnormally rapid growth [Higham et al 2010, Dutta et al 2019]. Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	AIP Familial Isolated Pituitary Adenomas	None	29,835	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK97965/	2021-01-18T21:45:28	{"synonyms": []}
Euryblepharon is a rare congenital eyelid anomaly of unknown etiology characterized by the bilateral horizontal enlargement of the palpebral fissure with vertically shortened eyelids, lateral canthus malpositioning and lateral ectropion. It may be isolated or associated with other ocular anomalies (e.g. strabismus or telecanthus; see this term) or systemic anomalies (e.g. blepharo-cheilo-odontic syndrome, see this term). In severe cases, it may result in lagophthalmos and exposure keratopathy, requiring surgical treatment. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Euryblepharon	c1303001	29,836	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99172	2021-01-23T18:33:52	{"icd-10": ["Q10.1"]}
Branchio-oculo-facial syndrome Other namesHemangiomatous branchial clefts-lip pseudocleft syndrome Autosomal dominant is the manner of inheritance of this condition Branchio-oculo-facial syndrome (BOFS)[1] is a disease that arises from a mutation in the TFAP2A gene. It is a rare autosomal dominant disorder that starts to affect a child's development before birth.[1] Symptoms of this condition include skin abnormalities on the neck, deformities of the ears and eyes, and other distinctive facial features such a cleft lip along with slow growth, mental retardation and premature graying of hair.[2] ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 3 Diagnosis * 4 Management * 5 Epidemiology * 6 References * 7 External links ## Signs and symptoms[edit] "Branchio" refers to the branchial arches, also known as the pharyngeal arches, of the affected individual. The branchial arches are structures in the developing embryo that give rise to certain tissues in the neck and facial area. In individuals affected by this condition, the branchial arches fail to develop properly. This leads to some of the physical conditions of this syndrome, which include abnormal patches of skin on the neck and face region and can be abnormally hairy, thin or red and with a high number of blood vessels.[clarification needed] "Oculo" refers to the eyes. Individuals have vision impairment due to several malformations in the eyes such as small eyeballs, blockage in the tear ducts or lacking eyes completely. "Facial" refers to the face; those affected can have several abnormalities in that region. These abnormalities include a cleft lip, a cleft palate which is an opening in the roof of the mouth, widely spaced eyes (hypertelorism), sharp corners of the mouth that point upward, a broad nose that can include a flattened tip, along with several deformations of both the external and middle ear structures. This syndrome is restricted to the face, but it can also cause underdeveloped or malformed kidneys.[3] ## Pathophysiology[edit] The disease is genetically inherited and stems from a mutation that deletes the TFAP2A gene. This gene is important because it provides the blueprint for the arrangement of 437 amino acids that make up the protein transcription factor known as AP-2 alpha. This protein transcription factor binds to a carboxy terminus helix-span-helix motif and an amino terminus portion of DNA that affects the activity of numerous cellular activities such as cell division and apoptosis.[clarification needed] AP-2 alpha is especially important during the embryos development principally in the development of the branchial arches. Currently there are also four other proteins that are affected by the deletion of TFAP2A gene as well. One is L249P, this protein changes to cause a conformational space change with a substituted proline. Furthermore, a change in the R254W and R255G proteins results in a replacement of a charged polar side chain by a nonpolar side chain,[clarification needed] and lastly, an alteration in the G262E protein results in a nonpolar side chain being replaced by a charged polar side chain.[1] ## Diagnosis[edit] Branchio-oculo-facial syndrome is difficult to diagnose because it has incomplete penetrance. It is often misdiagnosed as branchio-oto-renal syndrome because of their similarities in symptoms.[medical citation needed] ## Management[edit] The care and management of people with BOFS is aimed at the specific signs and symptoms, and should be carried out by a multi-specialty team who are skilled in craniofacial disorders. A medical geneticist usually makes the clinical diagnosis, which is confirmed with molecular testing. Reconstructive surgery is needed to repair facial deformities and obstructed nasal ducts. Importantly, the skin defects should not be treated with simple cauterization. Strabismus (“crossed eyes”) may be corrected by surgery. In addition, people with BOFS should be managed by an ophthalmologist, otolaryngologist, dentist, and speech therapist. Depending on the person’s issues, there may be a need for a neuropsychologic or developmental evaluation and mental health support. Genetic counseling is recommended for the patients and their families for reproductive health. [4] ## Epidemiology[edit] It was estimated that only 100 cases of BOFS have been documented in the medical literature as of 2018 .[5] ## References[edit] 1. ^ a b c Milunsky, Jeff; Tom A. Maher; Geping Zhao; Amy E. Roberts; Heather J. Stalker; Roberto T. Zori; Michelle N. Burch; Michele Clemens; John B. Mulliken; Rosemarie Smith; Angela E. Lin (9 May 2008). "TFAP2A Mutations Result in Branchio-Oculo-Facial Syndrome". The American Journal of Human Genetics. 0002-9297. 82 (5): 1171–1177. doi:10.1016/j.ajhg.2008.03.005. PMC 2427243. PMID 18423521. 2. ^ Kulkarni, ML; S Deshmukh; A Kumar; PM Kulkarni (1 August 2005). "Branchio-oculo-facial syndrome Pseudo cleft". The Indian Journal of Pediatrics. 0019-5456. 72 (8): 701–703. doi:10.1007/BF02724081. PMID 16131778. 3. ^ Raveh, Eyal; Blake C. Papsin; Vito Forte (30 June 2000). "Branchio-oculo-facial syndrome". International Journal of Pediatric Otorhinolaryngology. 0165-5876. 53 (20): 149–156. doi:10.1016/S0165-5876(00)00310-4. PMID 10906521. 4. ^ "Branchio Oculo Facial Syndrome". National Organization for Rare Disorders (NORD). Retrieved 25 March 2019. 5. ^ "Branchio Oculo Facial Syndrome". National Organization for Rare Disorders (NORD). Retrieved 25 March 2019. ## External links[edit] Classification D * ICD-10: Q18.8 * OMIM: 113620 * SNOMED CT: 449821007 External resources * Orphanet: 1297 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Branchio-oculo-facial syndrome	c0376524	29,837	wikipedia	https://en.wikipedia.org/wiki/Branchio-oculo-facial_syndrome	2021-01-18T19:10:40	{"gard": ["3212"], "mesh": ["D019280"], "umls": ["C0376524"], "orphanet": ["1297"], "wikidata": ["Q9390211"]}
A number sign (#) is used with this entry because of evidence that multiple mitochondrial dysfunctions syndrome-4 (MMDS4) is caused by homozygous or compound heterozygous mutation in the ISCA2 gene (615317) on chromosome 14q24. Description MMDS4 is an autosomal recessive neurodegenerative disorder that usually results in death in early childhood. Affected individuals have normal development for the first months of life, but thereafter show progressive loss of motor and social skills with hypotonia, spasticity, and nystagmus. Patients regress to a vegetative state with lack of eye contact and speech, and poor feeding. Most patients have optic atrophy, and some may develop seizures. Brain imaging shows diffuse leukodystrophy in the subcortical region, brainstem, cerebellum, and spinal cord. Laboratory studies tend to show increased CSF glycine and decreased activity of mitochondrial complex II; there may be additional biochemical evidence of mitochondrial dysfunction (summary by Alaimo et al., 2018). For a general description and a discussion of genetic heterogeneity of multiple mitochondrial dysfunctions syndrome, see MMDS1 (605711). Clinical Features Al-Hassnan et al. (2015) reported 5 unrelated consanguineous Arab families in which 6 children had a severe neurologic disorder characterized by onset of neuroregression between ages 3 and 7 months. Two of the families had similarly affected children who were deceased. All 6 patients regressed to a vegetative state with no speech; 4 died before age 5 years. There were no dysmorphic features, but all had spasticity and optic atrophy. Brain imaging showed extensive diffuse bilateral signal abnormalities in multiple brain regions. Skeletal muscle biopsy revealed atrophic and angulated fibers, and patient fibroblasts showed a depletion of mitochondrial DNA copy number and decreased activity of mitochondrial respiratory complex I. No metabolic abnormalities were detected. Alaimo et al. (2018) reported 2 unrelated patients, each born of consanguineous Saudi parents, with MMDS4. The patients had normal development in the first few months of life, but then showed motor regression with hypotonia, spasticity, loss of eye contact, and loss of social interaction. Additional features included optic atrophy with absent visual evoked potentials. One patient had mild skeletal abnormalities, including joint laxity, short fourth metacarpals, and cutaneous toe syndactyly. Laboratory studies in 1 of the patients showed increased CSF glycine, glutamate, and lactate, and decreased 5-methyltetrahydrofolate, although these were all normal in plasma. Metabolic studies in the other patient were not performed. Brain imaging in both patients showed significant leukodystrophy affecting subcortical regions, cerebellum, and brainstem, with extensive involvement of the spinal cord. Both families had a history of several additional patients with fatal infantile leukodystrophy. Alfadhel et al. (2018) reported 10 children from 9 unrelated consanguineous Saudi families with MMDS4. Many of the families had a history of death of other sibs affected with a similar disorder or of recurrent miscarriages. The patients all had normal early development, but presented between 3 and 7 months of age with loss of developmental milestones, including visual fixation, motor, and language skills, as well as the onset of nystagmus. They had axial hypotonia, poor feeding due to swallowing weakness, peripheral spasticity, and optic atrophy. Three patients had seizures, 2 of whom had single or rare controllable seizures. All patients deteriorated to a vegetative state with a feeding tube. Laboratory studies, when performed, showed inconsistent results: 2 patients had increased CSF glycine and CSF lactate, 3 patients had increased plasma glycine and/or lactate, and several patients had normal plasma levels of glycine and lactate. Brain imaging, performed on most patients, showed white matter abnormalities in the cerebrum, cerebellum, and brainstem, with sparing of the basal ganglia. Five patients died between 11 and 28 months of age, usually due to recurrent chest infections. Alfadhel et al. (2018) noted the phenotypic similarity to LBSL (611105), which is caused by mutation in the DARS2 gene (610956). Toldo et al. (2018) reported a female infant of Italian descent with MMDS4. She presented at age 2 months with progressive axial hypotonia, motor regression, feeding difficulties, nystagmus, and brisk tendon reflexes. EEG showed generalized slow wave activity. CSF showed increased lactate, and brain imaging showed diffuse T2-weighted hyperintensities in the cortex with extensive involvement of the spinal cord. Analysis of muscle tissue showed reduced activity of mitochondrial complexes II and IV. The patient developed rapidly progressive respiratory failure resulting in death at age 3 months. Inheritance The transmission pattern of MMDS4 in the families reported by Al-Hassnan et al. (2015) was consistent with autosomal recessive inheritance. Molecular Genetics In 6 children from 5 unrelated consanguineous Arab families with MMDS4, Al-Hassnan et al. (2015) identified a homozygous missense mutation in the ISCA2 gene (G77S; 615317.0001). The mutation, which was found by a combination of autozygosity mapping and exome sequencing, segregated with the disorder in the families, and haplotype analysis indicated a founder effect. Patient cells showed decreased expression of ISCA2, ISCA1 (611006), and IBA57 (615316). Functional studies of the ISCA2 variant were not performed, but Al-Hassnan et al. (2015) noted that the ISCA2 gene is an essential component involved in the assembly of a mitochondrial iron-sulfur cluster (4Fe-4S) important for electron transfer and mitochondrial function. In 2 unrelated patients, each born of consanguineous Saudi parents, with MMDS4, Alaimo et al. (2018) identified a homozygous G77S mutation in the ISCA2 gene. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Dermal fibroblasts from 1 of the patients showed diminished mitochondrial membrane potential, variably decreased or increased mitochondrial enzyme complexes, decreased oxygen consumption, and decreased ATP production compared to controls, consistent with mitochondrial dysfunction. There was a decrease in complex II activity and mildly decreased complex IV activity, with intact complexes I and III. The mitochondria also showed morphologic defects as well as decreased mtDNA content, to about 25% of normal values. Patient cells also showed decreased levels of protein lipoylation, indicating a defect in the production of lipoic acid, presumably due to faulty Fe-S cluster generation and specifically affecting the 4Fe-4S-dependent enzyme LIAS (607031). Knockdown of ISCA2 using shRNA resulted in similar cellular abnormalities and defects involving 4Fe-4S-dependent proteins, but not 2Fe-2S proteins. In 10 children from 9 unrelated consanguineous Saudi families with MMDS4, Alfadhel et al. (2018) identified the homozygous G77S founder mutation in the ISCA2 gene. Specific functional studies of the variant were not performed, but laboratory studies suggested a defect in the 4Fe-4S cluster. In an Italian infant with MMDS4, Toldo et al. (2018) identified compound heterozygous mutations in the ISCA2 gene (c.295delT, 615317.0002 and S112G, 615317.0003). The mutations, which were found by next-generation sequencing of a panel of genes associated with mitochondrial disorders, segregated with the disorder in the family. Functional studies of the variant were not performed. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Optic atrophy \- Loss of eye contact \- Nystagmus \- Visual impairment MUSCLE, SOFT TISSUES \- Hypotonia \- Atrophic fibers seen on biopsy \- Some abnormal aggregation of mitochondria NEUROLOGIC Central Nervous System \- Neurodevelopmental regression to a vegetative state \- Cognitive disability \- Spasticity \- Hyperreflexia \- Absent speech \- Leukodystrophy of the subcortical region, cerebellum, brainstem, and spinal cord \- Periventricular white matter abnormalities LABORATORY ABNORMALITIES \- Increased CSF glycine, glutamate, and lactate \- Fibroblasts show decreased mitochondrial complex II activity \- Mildly decreased complex IV activity \- Decreased mtDNA levels \- Decreased mitochondrial membrane potential \- Decreased oxidative phosphorylation and ATP production MISCELLANEOUS \- Onset in the first year of life \- Progressive disorder \- Death in early childhood may occur MOLECULAR BASIS \- Caused by mutation in the iron-sulfur cluster assembly 2 gene (ISCA2, 615317.0001 ) ▲ 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	MULTIPLE MITOCHONDRIAL DYSFUNCTIONS SYNDROME 4	c4225348	29,838	omim	https://www.omim.org/entry/616370	2019-09-22T15:49:06	{"doid": ["0080136"], "omim": ["616370"], "orphanet": ["457406"], "synonyms": [], "genereviews": ["NBK481904"]}
A rare, heterogeneous group of rheumatologic diseases characterized by arthritis which has an onset before 16 years of age, persists for more than 6 weeks, and is of unknown origin. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Juvenile idiopathic arthritis	c1444838	29,839	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=92	2021-01-23T18:23:09	{"mesh": ["D001171"], "umls": ["C0553662", "C1444838", "C3495559"], "icd-10": ["M08.0", "M08.1", "M08.2", "M08.3", "M08.4", "M08.8", "M08.9"], "synonyms": ["Juvenile chronic arthritis", "Juvenile rheumatoid arthritis"]}
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (February 2015) Autoimmune oophoritis SpecialtyGynecology Autoimmune oophoritis is a rare autoimmune disease where the body's own immune system attacks the ovaries.[1] This causes the ovaries to have inflammation, atrophy, and fibrosis. Such changes in the ovaries can cause them to not function properly. This disease is caused by primary ovarian insufficiency (POI), where reproduction and hormonal function of the ovaries stops before the age of 40. ## Contents * 1 Signs and symptoms * 2 Causes * 3 Genetics * 4 Mechanism/ Pathophysiology * 5 Diagnosis * 6 Prevension/Treatment * 7 Prognosis * 8 Epidemiology * 9 Research * 10 References * 11 External links ## Signs and symptoms[edit] Autoimmune oophoritis can present with a wide variety of symptoms. It begins with the main symptom, which is amenorrhea, where there is an irregular or no menstrual period at all. Other symptoms are related to ovarian cysts, and more common ones are also listed below. A variation of symptoms can occur together, however, that depends on the person and the severity of the disease. * Primary amenorrhea * This amenorrhea is more specific to menstruation never occurring before. * Secondary amenorrhea * This type of amenorrhea is where menstruation occurred once puberty began but then suddenly stopped later on. * Infertility * Cramping * Bloating * Nausea * Vomiting * Sex hormone deficiency * Hot flushes * Lower abdominal pain * Fever * Malaise * Vaginal discharge * Symptoms associated with other coexisting autoimmune conditions ## Causes[edit] The underlying cause of autoimmune oophoritis is yet unknown. However, it is known that it can co-exit with lupus, pernicious anemia, myasthenia gravis, or other autoimmune conditions. Autoimmune oophoritis can also be associated with autoimmune endocrinopathy syndrome type I and type II.[2] These conditions can coexists because they are all autoimmune diseases, this is called polyautoimmunity. There are some environmental causes for autoimmune diseases that have been discovered in different studies. Those consist of exposures to chemicals in the environment, such as vinyl chloride, metals, mycotoxins, and organic compounds.[3] ## Genetics[edit] As Autoimmune oophoritis often occurs in the setting of autoimmune polyendocrine syndromes (APS), mutations in AIRE or HLA-DR3/4 can contribute to its pathology.[4] ## Mechanism/ Pathophysiology[edit] There is no set mechanism specifically for autoimmune oophoritis, but it is known that microscopic examinations reveal a picture of inflammatory infiltrate. Selectively attacking the developing follicles and corpus luteum with sparing of the primordial follicles. However, since it is an autoimmune disease, it occurs when the immune system develops a response against one or more of the body's normal functions as if they were harmful. Then, the immune system fails to differentiate between "self" and "non-self", therefore it begins to develop antibodies. Antibodies target its own cells, tissues, and organs. Antibodies are made by the immune system as a response to an infection. They are produced by B cells, which are made in the bone marrow and found in the blood.[5] Antibodies are Y-shaped which allows them to work properly because that is how their unique sites bind with a matching site on antigens. That is where they destroy them. Research has shown that Theca cells could be part of a potential mechanism but more research should be done to verify the results. ## Diagnosis[edit] Diagnosis includes a blood test that looks for anti-steroid or anti-ovarian antibodies[6] in the bloodstream to confirm infertility in the female. Antibodies result as a response to an infection that the body has already fought. Anti-ovarian antibodies are found against the ovaries, they bind to the working sites of the ovaries. According to research anti-ovarian antibodies cause malfunctions in the ovulation process.[7] Pelvic ultrasounds are also done to look for enlarged cystic ovaries. In other cases biopsies may be required in order to confirm the diagnosis. Other type of tests could be done to rule out other issues that can be a part of primary ovarian insufficiency (POI).[2] ## Prevension/Treatment[edit] There is no specific treatment for autoimmune oophoritis yet. Nor is there an immunosuppressive that has shown to be effective and safe. However, affected women are usually started on hormone replacement therapies, or corticosteroids to achieve immunosuppression. A few risk factors associated with the hormone replacement therapies are: breast cancer, endometrial cancer, and ovarian cancer.[8] Women with this disease need a lot of emotional support and should maintain a management of other autoimmune conditions. ## Prognosis[edit] The prognosis is difficult to evaluate given the rarity of this condition, some patients with autoimmune oophoritis may have intermittent ovarian follicle function and may ovulate spontaneously. Allowing them to menstruate normally and even achieve pregnancy after therapy.[4] ## Epidemiology[edit] Autoimmune oophoritis accounts for almost 4% of women who present with primary ovarian insufficiency (POI). However, due to the lack of awareness and systematic studies, the ethnicity related prevalence is not known yet.[9] Since autoimmune oophoritis is listed as a "rare disease" by the Office of Rare Diseases (ORD) of the National Institutes of Health (NIH), it means that less than 200,000 women in the United States are affected by it.[10] ## Research[edit] In 2015 a research was done on the role of autoimmunity in premature ovarian failure.[11] In 2014 there was an ovarian autoimmune disease research that revealed at least two mechanisms that protect the ovary from an autoimmune attack.[12] Research showed that Theca cells were targeting the autoimmune deficiency within the ovary. And in 2011, a research was done on a patient who suffered from myasthenia gravis (MG) in conjunction with autoimmune oophoritis whose premature ovarian insufficiency was cured without hormonal therapy, only after thymectomy.[13] The study suggests treatment of MG including thymectomy could cure ovarian failure and hormonal therapy may not be necessary. ## References[edit] 1. ^ Noel R. Rose; Ian R. Mackay (2006). The autoimmune diseases (4th ed.). St. Louis, MO: Elsevier Academic Press. ISBN 978-0-12-595961-2. 2. ^ a b "Autoimmune oophoritis". NIH.gov. 6 June 2016. Retrieved 2018-08-07. 3. ^ "Autoimmune Diseases Research Papers on Genetics and Environmental Factors". www.papermasters.com. Retrieved 2020-12-18. 4. ^ a b Welt, Corrine K. (2008). "Autoimmune oophoritis in the adolescent". Annals of the New York Academy of Sciences. 1135 (1): 118–122. Bibcode:2008NYASA1135..118W. doi:10.1196/annals.1429.006. ISSN 0077-8923. PMID 18574216. S2CID 12016629. 5. ^ "Do Antibodies Mean Immunity?". Dictionary.com. 2020-05-05. Retrieved 2020-12-18. 6. ^ Welt CK (2008). "Autoimmune oophoritis in the adolescent". Ann. N. Y. Acad. Sci. 1135 (1): 118–22. Bibcode:2008NYASA1135..118W. doi:10.1196/annals.1429.006. PMID 18574216. S2CID 12016629. 7. ^ "Anti Ovarian Antibody Test - Test Results, Normal Range, Cost And More". Lybrate. Retrieved 2020-12-18. 8. ^ "Hormone Replacement Therapy (Risks and Benefits). HRT". patient.info. Retrieved 2020-12-18. 9. ^ Bakalov, Vladimir K.; Anasti, James N.; Calis, Karim A.; Vanderhoof, Vien H.; Premkumar, Ahalya; Chen, Shu; Furmaniak, Jadwiga; Smith, B. Rees; Merino, Maria J. (October 2005). "Autoimmune oophoritis as a mechanism of follicular dysfunction in women with 46,XX spontaneous premature ovarian failure". Fertility and Sterility. 84 (4): 958–965. doi:10.1016/j.fertnstert.2005.04.060. ISSN 1556-5653. PMID 16213850. 10. ^ "What is Autoimmune oophoritis? - RightDiagnosis.com". www.rightdiagnosis.com. Retrieved 2020-11-10. 11. ^ Ebrahimi, Mahbod; Akbari Asbagh, Firouzeh (August 2015). "The role of autoimmunity in premature ovarian failure". Iranian Journal of Reproductive Medicine. 13 (8): 461–472. ISSN 1680-6433. PMC 4637110. PMID 26568748. 12. ^ Warren, Bryce D.; Kinsey, William K.; McGinnis, Lynda K.; Christenson, Lane K.; Jasti, Susmita; Stevens, Anne M.; Petroff, Brian K.; Petroff, Margaret G. (November 2014). "Ovarian autoimmune disease: clinical concepts and animal models". Cellular & Molecular Immunology. 11 (6): 510–521. doi:10.1038/cmi.2014.97. ISSN 2042-0226. PMC 4220844. PMID 25327908. 13. ^ Çakır, Esra Deniz Papatya; Özdemir, Özlem; Eren, Erdal; Sağlam, Halil; Okan, Mehmet; Tarım, Ömer Faruk (2011). "Resolution of autoimmune oophoritis after thymectomy in a myasthenia gravis patient". Journal of Clinical Research in Pediatric Endocrinology. 3 (4): 212–215. doi:10.4274/jcrpe.378. ISSN 1308-5735. PMC 3245496. PMID 22155465. This article incorporates public domain material from websites or documents of the National Institutes of Health. ## External links[edit] Classification D * MeSH: C538274 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Autoimmune oophoritis	c0878654	29,840	wikipedia	https://en.wikipedia.org/wiki/Autoimmune_oophoritis	2021-01-18T18:59:25	{"gard": ["9461"], "mesh": ["C538274"], "umls": ["C0878654"], "wikidata": ["Q20707781"]}
A number sign (#) is used with this entry because complement factor D deficiency (CFDD) is caused by homozygous mutation in the CFD gene (134350) on chromosome 19p13. Description Complement factor D deficiency is an autosomal recessive immunologic disorder characterized by increased susceptibility to bacterial infections, particularly Neisseria infections, due to a defect in the alternative complement pathway (summary by Biesma et al., 2001). Clinical Features Kluin-Nelemans et al. (1984) described a partial functional deficiency of factor D in 2 Dutch adult monozygous female twins with recurrent bacterial respiratory infections since childhood. Hiemstra et al. (1989) reported a 24-year-old Dutch man with recurrent Neisseria infections. Laboratory studies found no detectable serum complement factor D hemolytic activity, and absence of measurable amounts of factor D antigen. Addition of purified factor D to the patient's serum restored full activity of the alternative complement pathway. The sister and the father, as well as the parents of the mother, had factor D levels within the normal range; the factor D level of the mother was decreased. Biesma et al. (2001) reported a 23-year-old Dutch woman, born of consanguineous parents, with septic shock due to Neisseria meningitidis in blood and cerebrospinal fluid. A deceased family member had a history of recurrent bacterial meningitis. Laboratory studies showed absence of factor D activity in the proband. However, absence of factor D activity was also found in 3 family members who did not have a history of recurrent infections. Combined with the earlier observation of Hiemstra et al. (1989), this finding suggested that factor D deficiency predisposes to invasive meningococcal disease. None of the reported patients was obese. Sprong et al. (2006) reported a Turkish brother and sister with invasive meningococcal disease. The 19-month-old girl was admitted with purpura, high fever, coughing, diarrhea, and vomiting. Cerebrospinal fluid cultures grew N. meningitidis. She died in refractory shock about 47 hours after hospital admission. Four years later, the 13-month-old brother was admitted to the same hospital because of sudden onset of fever and a petechial rash. At the age of 4 months, he had been hospitalized for a respiratory syncytial virus infection complicated by bacterial superinfection. Blood cultures grew N. meningitidis. Immunologic studies indicated that factor D was undetectable. Because of this deficiency, the boy was put on antibiotic prophylaxis and was vaccinated for N. meningitidis. Inheritance Complement factor D deficiency is inherited in an autosomal recessive pattern (Biesma et al., 2001). Molecular Genetics In a Dutch family with factor D deficiency, Biesma et al. (2001) identified a homozygous mutation in the CFD gene (134350.0001). In 2 children of a Turkish family with N. meningitis due to complement factor D deficiency, Sprong et al. (2006) identified a homozygous mutation in the factor D gene (134350.0002). INHERITANCE \- Autosomal recessive IMMUNOLOGY \- Increased susceptibility to bacterial infections \- Increased susceptibility to Neisseria infection LABORATORY ABNORMALITIES \- Decreased complement factor D \- Decreased activity of complement factor D MISCELLANEOUS \- Variable severity MOLECULAR BASIS \- Caused by mutation in the complement factor D gene (CFD, 134350.0001 ) ▲ 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	COMPLEMENT FACTOR D DEFICIENCY	c0398764	29,841	omim	https://www.omim.org/entry/613912	2019-09-22T15:57:02	{"mesh": ["C565027"], "omim": ["613912"], "orphanet": ["169467"], "synonyms": ["Alternative titles", "FACTOR D DEFICIENCY"]}
Hypocalcemic vitamin D-dependent rickets (VDDR-I) is an early-onset hereditary vitamin D metabolism disorder characterized by severe hypocalcemia leading to osteomalacia and rachitic bone deformations, and moderate hypophosphatemia. ## Epidemiology The prevalence at birth is estimated at around 1/2,000. The disease is more frequent in the French Canadian population in the Saguenay region of Quebec. ## Clinical description The disease manifests within the first year of life with hypotonia, tetany, seizures, muscle weakness, and poor growth. Progressively, patients present with rachitic deformities (bowed legs, rachitic rosary...). Enamel hypoplasia is occasionally observed. ## Etiology The disease is due to inactivating mutations in the CYP27B1 gene (12q14) that codes for 1-alpha-hydroxylase which converts the vitamin D precursor calcidiol to calcitriol, the vitamin D active metabolite. This defect in the synthesis of vitamin D leads to defective intestinal absorption of calcium and phosphate. ## Diagnostic methods Diagnosis is based on biochemical and radiological findings. Classic radiological signs of rickets are skeletal anomalies of the growth plates and metaphyseal bones, osteomalacia, and osteoporosis. Biochemical findings are severe hypocalcemia and moderate hypophosphatemia. Additional biochemical anomalies include normal serum levels of calcidiol (25-hydroxyvitamin D) associated with low serum levels of calcitriol (1,25-dihydroxyvitamin D3), aminoaciduria and elevated peripheral parathyroid hormone concentrations. Bone biopsy can reveal osteomalacia. Diagnosis is confirmed by DNA analysis. ## Differential diagnosis Differential diagnosis includes nutritional vitamin D deficiency, vitamin D resistant rickets (see this term) and bone dysplasia. ## Genetic counseling Transmission is autosomal recessive. ## Management and treatment Treatment aims at improving growth and restoring normal serum levels of calcium, phosphorus, alkaline phosphatase, and parathyroid hormone and at healing/preventing skeletal deformities. It consists of daily administration of large doses of vitamin D and physiologic doses of calcitriol. Nephrocalcinosis, hypercalciuria, and hypercalcemia can be observed as complications of the therapy. Regular monitoring (physical and biochemical examination, hand radiographs, renal ultrasound) is thus required. ## Prognosis With treatment, prognosis is good. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Hypocalcemic vitamin D-dependent rickets	c0268689	29,842	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=289157	2021-01-23T19:10:03	{"mesh": ["C562688"], "omim": ["264700", "600081"], "umls": ["C0268689"], "icd-10": ["E55.0"], "synonyms": ["1-alpha-hydroxylase deficiency", "PDDRI", "Pseudovitamin D-deficient rickets", "VDDI", "VDDR-I", "Vitamin D dependent rickets type I", "Vitamin D-dependency type I"]}
A number sign (#) is used with this entry because of evidence that early infantile epileptic encephalopathy-5 (EIEE5) is caused by heterozygous mutation in the SPTAN1 gene (182810) on chromosome 9q34. For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350). Clinical Features Tohyama et al. (2008) reported 2 unrelated Japanese infants, a girl and a boy, with early infantile epileptic encephalopathy. Both had onset of intractable seizures associated with hypsarrhythmia at age 3 months. Both had profound mental retardation with lack of visual attention and speech development, as well as spastic quadriplegia. Brain MRI showed diffuse hypomyelination and widespread brain atrophy affecting the cortex, corpus callosum, brainstem, and cerebellum. Progressive microcephaly was also observed. Hamdan et al. (2012) reported an 11-year-old French Canadian boy with EIEE5 and severe intellectual disability. Although he did not present with early infantile spasms, he had febrile seizures at age 16 months and later developed mild generalized epilepsy. He could not walk or speak, but did understand a few commands and was able to communicate with a few signs. He had hypotonia, but no microcephaly or dysmorphic features. Brain MRI showed severe atrophy of the cerebellum and mild atrophy of the brainstem, without any hypomyelination or other structural defects. Overall, the phenotype in this patient was less severe than that of the patients reported by Saitsu et al. (2010). Writzl et al. (2012) reported an 8-month-old Slovenian girl with EIEE5. Significant hypotonia had been apparent since birth. She had no visual contact, and ophthalmologic examination revealed bilateral coloboma-like optic discs. An abnormal EEG was noted on the third day of life; the patient subsequently developed intractable seizures with hypsarrhythmia and suppression burst-like pattern on EEG. Psychomotor development was severely impaired. Brain MRI showed hypomyelination, reduction of deep and subcortical white matter, and thin corpus callosum. Dysmorphic features included small anterior fontanel, low-set ears, and high-arched palate. Nonoda et al. (2013) reported a 12-month-old Japanese boy with EIEE5 who developed seizures associated with hypsarrhythmia at 3 months of age. Brain imaging showed progressive atrophy of the brain, predominantly at the brainstem and cerebellum, and severe hypomyelination. He had progressive microcephaly (-3.2 SD at 7 months of age), severely impaired psychomotor development, no visual attention, and rigospastic tetraplegia. Genetic analysis identified a de novo heterozygous mutation in the SPTAN1 gene (182810.0005). Molecular Genetics In 2 unrelated Japanese patients with EIEE5, previously reported by Tohyama et al. (2008), Saitsu et al. (2010) identified different de novo heterozygous mutations (182810.0001-182810.0002) in the SPTAN1 gene. In vitro functional expression studies suggested a dominant-negative effect of the mutations on spectrin heterodimer stability, as well as perturbation of the axon initial segment. Another unrelated patient with a similar disorder, previously reported by Tohyama et al. (2008) and Saitsu et al. (2008), was found to have a 2.25-Mb microdeletion encompassing both the STXBP1 (602926) and SPTAN1 genes. This patient had a slightly milder phenotype with well-controlled seizures and only mildly decreased white matter with no structural brain anomalies. Although she had hypomyelination at 12 months, she showed progression of myelination at age 4 years. Saitsu et al. (2010) hypothesized that this patient's phenotype was due more to haploinsufficiency of STXBP1 (see EIEE4; 612164), but that haploinsufficiency of SPTAN1 may have had some effect on myelination. In an 11-year-old French Canadian boy with EIEE5, Hamdan et al. (2012) identified a de novo heterozygous mutation in the SPTAN1 gene (182810.0003). In vitro expression of the mutation in primary mouse cortical neurons caused formation of spectrin aggregates in about 20% of cells. INHERITANCE \- Autosomal dominant HEAD & NECK Head \- Microcephaly, progressive (in some patients) Eyes \- No visual attention \- Coloboma-like optic discs (1 patient) NEUROLOGIC Central Nervous System \- Seizures, tonic, intractable \- Mental retardation, severe to profound \- Lack of speech development \- Lack of visual attention \- Hypsarrhythmia \- Spastic quadriplegia \- Hyperreflexia \- Lack of independent ambulation \- Hypotonia \- Diffuse hypomyelination \- Widespread brain atrophy \- Thin corpus callosum \- Cerebral atrophy \- Brainstem atrophy \- Cerebellar atrophy MISCELLANEOUS \- Onset in infancy \- Variable severity MOLECULAR BASIS \- Caused by mutation in the nonerythrocytic alpha-spectrin 1 gene (SPTAN1, 182810.0001 ) ▲ 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	EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 5	c0037769	29,843	omim	https://www.omim.org/entry/613477	2019-09-22T15:58:33	{"doid": ["0080438"], "mesh": ["D013036"], "omim": ["613477"], "orphanet": ["3451"]}
Osteochondritis dissecans is a joint condition that occurs when a piece of cartilage and the thin layer of bone beneath it, separates from the end of the bone. If the piece of cartilage and bone remain close to where they detached, they may not cause any symptoms. However, affected people may experience pain, weakness and/or decreased range of motion in the affected joint if the cartilage and bone travel into the joint space. Although osteochondritis dissecans can affect people of all ages, it is most commonly diagnosed in people between the ages of 10 and 20 years. In most cases, the exact underlying cause is unknown. Rarely, the condition can affect more than one family member (called familial osteochondritis dissecans); in these cases, osteochondritis dissecans is caused by changes (mutations) in the ACAN gene and is inherited in an autosomal dominant manner. Treatment for the condition varies depending on many factors, including the age of the affected person and the severity of the symptoms, but may include rest; casting or splinting; surgery and/or physical therapy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and 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 osteochondritis dissecans	c3665488	29,844	gard	https://rarediseases.info.nih.gov/diseases/4133/familial-osteochondritis-dissecans	2021-01-18T18:00:33	{"mesh": ["C580095"], "omim": ["165800"], "orphanet": ["251262"], "synonyms": ["Osteochondritis dissecans, short stature, and early-onset osteoarthritis "]}
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: "Chromosome 2q deletion" – news · newspapers · books · scholar · JSTOR (December 2018) (Learn how and when to remove this template message) This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (March 2018) Chromosome 2q deletion is a chromosome abnormality that occurs when there is a missing copy of the genetic material located on the long arm (q) of chromosome 2. The severity of the condition and the signs and symptoms depend on the size and location of the deletion, and which genes are involved. Features that often occur in people with chromosome 2q deletion include developmental delay, intellectual disability, behavior problems, and distinctive facial features. Most cases are not inherited, but people can pass the deletion on to their children. Treatment is based on the signs and symptoms present in each person.[1] ## See also[edit] * 2q37 deletion syndrome ## References[edit] 1. ^ "Chromosome 2q deletion - Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 12 August 2017. This article incorporates text from this source, which is in the public domain. This genetic disorder article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Chromosome 2q deletion	c0795804	29,845	wikipedia	https://en.wikipedia.org/wiki/Chromosome_2q_deletion	2021-01-18T18:42:02	{"gard": ["3744"], "mesh": ["C538315"], "umls": ["C0795804"], "orphanet": ["262010"], "wikidata": ["Q39048665"]}
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: "Burusera" – news · newspapers · books · scholar · JSTOR (June 2010) (Learn how and when to remove this template message) A Japanese vending machine selling used panties for fetish purposes Burusera (ブルセラ) is a paraphilia, specifically a sexualized attraction to the underwear or school uniforms of girls or young women. It is a word of Japanese origin, coined by combining burumā (ブルマー), meaning bloomers, as in the bottoms of gym suits, and sērā-fuku (セーラー服), meaning sailor suit, the traditional Japanese school uniforms for schoolgirls; notably kogal.[1][2][3] Burusera shops sell girls' used school uniforms, panties and other fetish items. ## Contents * 1 History * 2 Burusera shops * 3 Legal restrictions * 4 References in media * 5 See also * 6 References * 7 External links ## History[edit] In the 1990s gravure magazines started to feature photos of girls wearing bloomers and school uniforms, some magazines featuring exclusively those types of clothes. Fetish shops selling these types of clothes also started appearing in Japan. Along with loose socks they became the symbol of high school girls in the 1990s. They are also sometimes worn as cosplay. ## Burusera shops[edit] Burusera shops sell used girls' gym suits and school uniforms. They also sell other goods procured from schoolgirls, e.g. undergarments, school swimsuits for physical education, socks, stationery, sanitary napkins and tampons. The clothes are often accompanied by ostensibly genuine photos of the girls wearing them. The clients are men who use the items for sexual arousal or stimulation. Schoolgirls once openly participated in the sale of their used garments, either through burusera shops or using mobile phone sites to sell directly to clients. ## Legal restrictions[edit] In August 1994, a burusera shop manager who made a schoolgirl sell her used underwear was arrested by the Tokyo Metropolitan Police Department on suspicion of violation of article 34 of the Child Welfare Act and article 175 of the Criminal Code. The police alleged violations of the Secondhand Articles Dealer Act which bans the purchase of secondhand goods without authorization.[4] Child pornography laws imposed legal control over the burusera industry in 1999.[5] However, burusera goods in themselves are not child pornography, and selling burusera goods is an easy way for schoolgirls to gain extra income. This has been viewed with suspicion as child sexual abuse.[6] Prefectures in Japan began enforcing regulations in 2004 that restricted purchases and sales of used underwear and saliva of people under 18.[7] ## References in media[edit] * In the Shin Kimagure Orange Road novel Summer's Beginning, main character Kyosuke Kasuga is disgusted when he finds out that his now highschool-aged younger sister Kurumi intends to sell her used leotards to a burusera shop.[8] * In the visual novel True Love, a key part to Mayumi Kamijou's route involves the Player Character, Daisuke, finding out that she intends to sell a pair of her panties in the local burusera shop. If Daisuke finds said panties, keeps them and gives them back to Mayumi when she asks for them, he will gain relationship points with her. * In the computer game Yandere Simulator, the player, Ayano Aishi, can purchase a "dark secret" from Info-Chan as a favor. Info-Chan sends her a text saying that she has video footage of Kokona Haruka, one of Ayano's rivals, selling used panties to a boy from another school. * In the video game Yakuza 0, a side quest involves the discovery, and ultimately the taking down, of a burusera ring. * One of the characters in the novel Consumed, by the Canadian film director David Cronenberg, references it while talking about school uniforms. ## See also[edit] * Clothing fetish * Uniform fetishism * Panty fetishism * Shoe fetishism * Child pornography laws in Japan * Panchira * Zettai ryōiki * AV idol * JK business * Cosplay restaurant * Host and hostess clubs * Maid café * Hentai * Kogal * Gyaru * Upskirt ## References[edit] 1. ^ "The economics of pricing used panties." http://aprilsbody.com/used-panties-prices-explained/ Archived 2014-02-22 at the Wayback Machine (Retrieved on Feb. 16, 2014). 2. ^ Telegraph news report 3. ^ Sydney Morning Herald news report 4. ^ 警察白書 (Police White Paper), 1994. (in Japanese) 5. ^ 児童買春，児童ポルノに係る行為等の処罰及び児童の保護等に関する法律 (Act on Punishment of Activities Relating to Child Prostitution and Child Pornography, and the Protection of Children) 6. ^ The Ninth United Nations Congress on the Prevention of Crime and the Treatment Offenders Cairo, Egypt: A Report from the Japan Federation of Bar Associations to the Ninth United Nations Congress on the Prevention of Crime and the Treatment of Offenders, March 1995, Japan Federation of Bar Associations. Archived April 8, 2011, at the Wayback Machine 7. ^ 東京都青少年の健全な育成に関する条例 (Tokyo Metropolitan Ordinance on Juvenile Protection) Articles 15, 15-2 and 15-3. Archived 2013-10-03 at the Wayback Machine (in Japanese) 8. ^ Shin Kimagure Orange Road: Summer's Beginning. ## External links[edit] * DNA India 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	Burusera	None	29,846	wikipedia	https://en.wikipedia.org/wiki/Burusera	2021-01-18T18:34:49	{"wikidata": ["Q2725587"]}
Medical condition affecting newborn infants Meconium aspiration syndrome Other namesNeonatal aspiration of meconium X-ray showing the extent of lung epithelial damage in response to meconium seen in neonates with meconium aspiration syndrome. SpecialtyNeonatology Meconium aspiration syndrome (MAS) also known as neonatal aspiration of meconium is a medical condition affecting newborn infants. It describes the spectrum of disorders and pathophysiology of newborns born in meconium-stained amniotic fluid (MSAF) and have meconium within their lungs. Therefore, MAS has a wide range of severity depending on what conditions and complications develop after parturition. Furthermore, the pathophysiology of MAS is multifactorial and extremely complex which is why it is the leading cause of morbidity and mortality in term infants.[1][2] The word meconium is derived from the Greek word mēkōnion meaning juice from the opium poppy as the sedative effects it had on the foetus were observed by Aristotle.[3] Meconium is a sticky dark-green substance which contains gastrointestinal secretions, amniotic fluid, bile acids, bile, blood, mucus, cholesterol, pancreatic secretions, lanugo, vernix caseosa and cellular debris.[1] Meconium accumulates in the foetal gastrointestinal tract throughout the third trimester of pregnancy and it is the first intestinal discharge released within the first 48 hours after birth.[4] Notably, since meconium and the whole content of the gastrointestinal tract is located ‘extracorporeally,’ its constituents are hidden and normally not recognised by the foetal immune system.[5] For the meconium within the amniotic fluid to successfully cause MAS, it has to enter the respiratory system during the period when the fluid-filled lungs transition into an air-filled organ capable of gas exchange.[1] ## Contents * 1 Causes * 1.1 Meconium passage as a result of foetal distress * 1.2 Meconium passage as a result of foetal maturity * 2 Pathophysiology * 2.1 Airway obstruction * 2.2 Foetal hypoxia * 2.3 Infection * 2.4 Pulmonary inflammation * 2.5 Surfactant inactivation * 2.6 Persistent Pulmonary Hypertension * 2.7 Apoptosis * 3 Diagnosis * 4 Prevention * 4.1 Prevention during pregnancy * 4.2 Prevention during parturition * 5 Treatment * 5.1 Assisted ventilation techniques * 5.2 Inhaled nitric oxide * 5.3 Antiinflammatories * 5.3.1 Glucocorticoids * 5.3.2 Inhibitors of phosphodiesterase * 5.3.3 Inhibitors of cyclooxygenase * 5.4 Antibiotics * 5.5 Surfactant treatment * 5.6 Previous treatments * 6 Prevalence * 7 Future research * 8 See also * 9 References * 10 External links ## Causes[edit] The main theories of meconium passage into amniotic fluid are caused by fetal maturity or from foetal stress as a result of hypoxia or infection.[3] Other factors that promote the passage of meconium in utero include placental insufficiency, maternal hypertension, pre-eclampsia and maternal drug use of tobacco and cocaine.[6] However, the exact mechanism for meconium passage into the amniotic fluid is not completely understood and it may be a combination of several factors. ### Meconium passage as a result of foetal distress[edit] There may be an important association between foetal distress and hypoxia with MSAF.[2] It is believed that foetal distress develops into foetal hypoxia causing the foetus to defecate meconium resulting in MSAF and then perhaps MAS.[6] Other stressors which causes foetal distress, and therefore meconium passage, includes when umbilical vein oxygen saturation is below 30%.[3] Foetal hypoxic stress during parturition can stimulate colonic activity, by enhancing intestinal peristalsis and relaxing the anal sphincter, which results in the passage of meconium. Then, because of intrauterine gasping or from the first few breaths after delivery, MAS may develop. Furthermore, aspiration of thick meconium leads to obstruction of airways resulting in a more severe hypoxia.[6][7] It is important to note that the association between foetal distress and meconium passage is not a definite cause-effect relationship as over ¾ of infants with MSAF are vigorous at birth and do not have any distress or hypoxia.[2] Additionally, foetal distress occurs frequently without the passage of meconium as well.[3] ### Meconium passage as a result of foetal maturity[edit] Although meconium is present in the gastrointestinal tract early in development, MSAF rarely occurs before 34 weeks gestation.[3] Peristalsis of the foetal intestines is present as early as 8 weeks gestation and the anal sphincter develops at about 20–22 weeks. The early control mechanisms of the anal sphincter are not well understood, however there is evidence that the foetus does defecate routinely into the amniotic cavity even in the absence of distress. The presence of fetal intestinal enzymes have been found in the amniotic fluid of women who are as early as 14–22 weeks pregnant. Thus, suggesting there is free passage of the intestinal contents into the amniotic fluid.[8] Motilin is found in higher concentrations in post-term than pre-term foetal gastrointestinal tracts. Similarly, intestinal parasympathetic innervation and myelination also increases in later gestations. Therefore, the increased incidence of MAS in post-term pregnancies may reflect the maturation and development of the peristalsis within the gastrointestinal tract in the newborn.[3] ## Pathophysiology[edit] As MAS describes a spectrum of disorders of newborns born through MSAF, without any congenital respiratory disorders or other underlying pathology, there are numerous hypothesised mechanisms and causes for the onset of this syndrome. Long-term consequences may arise from these disorders, for example, infants that develop MAS have higher rates of developing neurodevelopmental defects due to poor respiration.[9] ### Airway obstruction[edit] In the first 15 minutes of meconium aspiration, there is obstruction of larger airways which causes increased lung resistance, decreased lung compliance, acute hypoxemia, hypercapnia, atelectasis and respiratory acidosis. After 60 minutes of exposure, the meconium travels further down into the smaller airways. Once within the terminal bronchioles and alveoli, the meconium triggers inflammation, pulmonary edema, vasoconstriction, bronchoconstriction, collapse of airways and inactivation of surfactant.[10][11] ### Foetal hypoxia[edit] The lung areas which do not or only partially participate in ventilation, because of obstruction and/or destruction, will become hypoxic and an inflammatory response may consequently occur. Partial obstruction will lead to air trapping and hyperinflation of certain lung areas and pneumothorax may follow. Chronic hypoxia will lead to an increase in pulmonary vascular smooth muscle tone and persistent pulmonary hypertension causing respiratory and circulatory failure.[1] ### Infection[edit] Microorganisms, most commonly Gram-negative rods, and endotoxins are found in samples of MSAF at a higher rate than in clear amniotic fluid, for example 46.9% of patients with MSAF also had endotoxins present. A microbial invasion of the amniotic cavity (MIAC) is more common in patients with MSAF and this could ultimately lead to an intra-amniotic inflammatory response. MIAC is associated with high concentrations of cytokines (such as IL-6), chemokines (such as IL-8 and monocyte chemoattractant protein-1), complement, phospholipase A2 and matrix-degrading enzymes. Therefore, these aforementioned mediators within the amniotic fluid during MIAC and intra-amniotic infection could, when aspirated in utero, induce lung inflammation within the foetus.[12] ### Pulmonary inflammation[edit] Meconium has a complex chemical composition, so it is difficult to identify a single agent responsible for the several diseases that arise. As meconium is stored inside the intestines, and is partly unexposed to the immune system, when it becomes aspirated the innate immune system recognises as a foreign and dangerous substance. The immune system, which is present at birth, responds within minutes with a low specificity and no memory in order to try to eliminate microbes. Meconium perhaps leads to chemical pneumonitis as it is a potent activator of inflammatory mediators which include cytokines, complement, prostaglandins and reactive oxygen species.[5] Meconium is a source of pro-inflammatory cytokines, including tumour necrosis factor (TNF) and interleukins (IL-1, IL-6, IL-8), and mediators produced by neutrophils, macrophages and epithelial cells that may injure the lung tissue directly or indirectly. For example, proteolytic enzymes are released from neutrophilic granules and these may damage the lung membrane and surfactant proteins. Additionally, activated leukocytes and cytokines generate reactive nitrogen and oxygen species which have cytotoxic effects. Oxidative stress results in vasoconstriction, bronchoconstriction, platelet aggregation and accelerated cellular apoptosis.[11] Recently, it has been hypothesised that meconium is a potent activator of toll-like receptor (TLRs) and complement, key mediators in inflammation, and may thus contribute to the inflammatory response in MAS.[1][5] Meconium contains high amounts of phospholipase A2 (PLA2), a potent proinflammatory enzyme, which may directly (or through the stimulation of arachidonic acid) lead to surfactant dysfunction, lung epithelium destruction, tissue necrosis and an increase in apoptosis.[1][11] Meconium can also activate the coagulation cascade, production of platelet-activating factor (PAF) and other vasoactive substances that may lead to destruction of capillary endothelium and basement membranes. Injury to the alveolocapillary membrane results in leakage of liquid, plasma proteins, and cells into the interstitium and alveolar spaces.[11] ### Surfactant inactivation[edit] Surfactant is synthesised by type II alveolar cells and is made of a complex of phospholipids, proteins and saccharides. It functions to lower surface tension (to allow for lung expansion during inspiration), stabilise alveoli at the end of expiration (to prevent alveolar collapse) and prevents lung oedema. Surfactant also contributes to lung protection and defence as it is also an anti-inflammatory agent. Surfactant enhances the removal of inhaled particles and senescent cells away from the alveolar structure.[13] The extent of surfactant inhibition depends on both the concentration of surfactant and meconium. If the surfactant concentration is low, even very highly diluted meconium can inhibit surfactant function whereas, in high surfactant concentrations, the effects of meconium are limited. Meconium may impact surfactant mechanisms by preventing surfactant from spreading over the alveolar surface, decreasing the concentration of surfactant proteins (SP-A and SP-B), and by changing the viscosity and structure of surfactant.[10] Several morphological changes occur after meconium exposure, the most notable being the detachment of airway epithelium from stroma and the shedding of epithelial cells into the airway. These indicate a direct detrimental effect on lung alveolar cells because of the introduction of meconium into the lungs.[1] ### Persistent Pulmonary Hypertension[edit] Persistent pulmonary hypertension (PPHN) is the failure of the foetal circulation to adapt to extra-uterine conditions after birth. PPHN is associated with various respiratory diseases, including MAS (as 15-20% of infants with MAS develop PPHN), but also pneumonia and sepsis. A combination of hypoxia, pulmonary vasoconstriction and ventilation/perfusion mismatch can trigger PPHN, depending on the concentration of meconium within the respiratory tract.[14][7] PPHN in newborns is the leading cause of death in MAS.[5] ### Apoptosis[edit] Apoptosis is an important mechanism in the clearance of injured cells and in tissue repair, however too much apoptosis may cause harm, such as acute lung injury. Meconium induces apoptosis and DNA cleavage of lung airway epithelial cells, this is detected by the presence of fragmented DNA within the airways and in alveolar epithelial nuclei. Meconium induces an inflammatory reaction within the lungs as there is an increase of autophagocytic cells and levels of caspase 3 after exposure. After 8 hours of meconium exposure, in rabbit foetuses, the total amount of apoptotic cells is 54%.[15] Therefore, the majority of meconium-induced lung damage may be due to the apoptosis of lung epithelium.[1] ## Diagnosis[edit] Release of meconium into the amniotic cavity and then intrauterine gasping of post-term neonates may cause meconium aspiration syndrome. Respiratory distress in an infant born through the darkly coloured MSAF as well as meconium obstructing the airways is usually sufficient enough to diagnose MAS. Additionally, newborns with MAS can have other types of respiratory distress such as tachypnea and hypercapnia. Sometimes it is hard to diagnose MAS as it can be confused with other diseases that also cause respiratory distress, such as pneumonia. Additionally, X-rays and lung ultrasounds can be quick, easy and cheap imaging techniques to diagnose lung diseases like MAS.[16] ## Prevention[edit] In general, the incidence of MAS has been significantly reduced over the past two decades as the number of post-term deliveries has minimised. Currently, labour is induced in women who have been pregnant for longer than 41 weeks gestation.[17] ### Prevention during pregnancy[edit] Prevention during pregnancy may include amnioinfusion and antibiotics but the effectiveness of these treatments are questionable.[2] ### Prevention during parturition[edit] As previously mentioned, oropharyngeal and nasopharyngeal suctioning is not an ideal preventative treatment for both vigorous and depressed (not breathing) infants.[2] ## Treatment[edit] Most infants born through MSAF do not require any treatments (other than routine postnatal care) as they show no signs of respiratory distress, as only approximately 5% of infants born through MSAF develop MAS.[1] However, infants which do develop MAS need to be admitted to a neonatal unit where they will be closely observed and provided any treatments needed. Observations include monitoring heart rate, respiratory rate, oxygen saturation and blood glucose (to detect worsening respiratory acidosis or the development of hypoglycemia).[18] In general, treatment of MAS is more supportive in nature. ### Assisted ventilation techniques[edit] To clear the airways of meconium, tracheal suctioning can be used however, the efficacy of this method is in question and it can cause harm.[19] In cases of MAS, there is a need for supplemental oxygen for at least 12 hours in order to maintain oxygen saturation of haemoglobin at 92% or more. The severity of respiratory distress can vary significantly between newborns with MAS, as some require minimal or no supplemental oxygen requirement and, in severe cases, mechanical ventilation may be needed.[20][2] The desired oxygen saturation is between 90-95% and PaO2 may be as high as 90mmHg.[17] In cases where there is thick meconium deep within the lungs, mechanical ventilation may be required. In extreme cases, extracorporeal membrane oxygenation (ECMO) may be utilised in infants who fail to respond to ventilation therapy.[2] While on ECMO, the body can have time to absorb the meconium and for all the associated disorders to resolve. There has been an excellent response to this treatment, as the survival rate of MAS while on ECMO is more than 94%.[21] Ventilation of infants with MAS can be challenging and, as MAS can affect each individual differently, ventilation administration may need to be customised. Some newborns with MAS can have homogenous lung changes and others can have inconsistent and patchy changes to their lungs. It is common for sedation and muscle relaxants to be used to optimise ventilation and minimise the risk of pneumothorax associated with dyssynchronous breathing.[18] ### Inhaled nitric oxide[edit] Inhaled nitric oxide (iNO) acts on vascular smooth muscle causing selective pulmonary vasodilation. This is ideal in the treatment of PPHN as it causes vasodilation within ventilated areas of the lung thus, decreasing the ventilation-perfusion mismatch and thereby, improves oxygenation. Treatment utilising iNO decreases the need for ECMO and mortality in newborns with hypoxic respiratory failure and PPHN as a result of MAS. However, approximately 30-50% of infants with PPHN do not respond to iNO therapy.[17] ### Antiinflammatories[edit] As inflammation is such a huge issue in MAS, treatment has consisted of anti-inflammatories. #### Glucocorticoids[edit] Glucocorticoids (GCs) have a strong anti-inflammatory activity and works to reduce the migration and activation of neutrophils, eosinophils, mononuclears and other cells. GCs reduce the migration of neutrophils into the lungs ergo, decreasing their adherence to the endothelium. Thus, there is a reduction in the action of mediators released from these cells and therefore, a reduced inflammatory response.[22][11] GCs also possess a genomic mechanism of action in which, once bound to a glucocorticoid receptor, the activated complex moves into the nucleus and inhibits transcription of mRNA. Ultimately, effecting whether various proteins get produced or not. Inhibiting the transcription of nuclear factor (NF-κB) and protein activator (AP-1) attenuates the expression of pro-inflammatory cytokines (IL-1, IL-6, IL-8 and TNF etc.), enzymes (PLA2, COX-2, iNOs etc.) and other biologically active substances.[23][22][11] The anti-inflammatory effect of GCs is also demonstrated by enhancing the activity of lipocortines which inhibit the activity of PLA2 and therefore, decrease the production of arachidonic acid and mediators of lipoxygenase and cyclooxygenase pathways.[22] Anti-inflammatories need to be administered as quickly as possible as the effect of these drugs can diminish even just an hour after meconium aspiration. For example, early administration of dexamethasone significantly enhanced gas exchange, reduced ventilatory pressures, decreased the number of neutrophils in the bronchoalveolar area, reduced oedema formation and oxidative lung injury.[11]However, GCs may increase the risk of infection and this risk increases with the dose and duration of glucocorticoid treatment. Other issues can arise, such as aggravation of diabetes mellitus, osteoporosis, skin atrophy and growth retardation in children.[23] #### Inhibitors of phosphodiesterase[edit] Phosphodiesterases (PDE) degrades cAMP and cGMP and, within the respiratory system of a newborn with MAS, various isoforms of PDE may be involved due to their pro-inflammatory and smooth muscle contractile activity. Therefore, non-selective and selective inhibitors of PDE could potentially be used in MAS therapy. However, the use of PDE inhibitors can cause cardiovascular side effects. Non-selective PDE inhibitors, such as methylxanthines, increase concentrations of cAMP and cGMP in the cells leading to bronchodilation and vasodilation. Additionally, methylxanthines decreases the concentrations of calcium, acetylcholine and monoamines, this controls the release of various mediators of inflammation and bronchoconstriction, including prostaglandins. Selective PDE inhibitors target one subtype of phosphodiesterase and in MAS the activities of PDE-3, PDE-4, PDE-5 and PDE-7 may become enhanced.[11] For example, Milrinone (a selective PDE3 inhibitor) improved oxygenation and survival of neonates with MAS.[24] #### Inhibitors of cyclooxygenase[edit] Arachidonic acid is metabolised, via cyclooxygenase (COX) and lipoxygenase, to various substances including prostaglandins and leukotrienes, which exhibit potent pro-inflammatory and vasoactive effects. By inhibiting COX, and more specifically COX-2, (either through selective or non-selective drugs) inflammation and oedema can be reduced. However, COX inhibitors may induce peptic ulcers and cause hyperkalemia and hypernatremia. Additionally, COX inhibitors have not shown any great response in the treatment of MAS.[11] ### Antibiotics[edit] Meconium is typically sterile however, it can contain various cultures of bacteria so appropriate antibiotics may need to be prescribed.[17] ### Surfactant treatment[edit] Lung lavage with diluted surfactant is a new treatment with potentially beneficial results depending on how early it is administered in newborns with MAS. This treatment shows promise as it has a significant effect on air leaks, pneumothorax, the need for ECMO and death. Early intervention and using it on newborns with mild MAS is more effective. However, there are risks as a large volume of fluid instillation to the lung of a newborn can be dangerous (particularly in cases of severe MAS with pulmonary hypertension) as it can exacerbate hypoxia and lead to mortality.[25] ### Previous treatments[edit] Originally, it was believed that MAS developed as a result of the meconium being a physical blockage of the airways. Thus, to prevent newborns, who were born through MSAF, from developing MAS, suctioning of the oropharyngeal and nasopharyngeal area before delivery of the shoulders followed by tracheal aspiration was utilised for 20 years. This treatment was believed to be effective as it was reported to significantly decrease the incidence of MAS compared to those newborns born through MSAF who were not treated.[26] This claim was later disproved and future studies concluded that oropharyngeal and nasopharyngeal suctioning, before delivery of the shoulders in infants born through MSAF, does not prevent MAS or its complications.[2] In fact, it can cause more issues and damage (e.g. mucosal damage), thus it is not a recommended preventative treatment.[19] Suctioning may not significantly reduce the incidence of MAS as meconium passage and aspiration may occur in-utero. Thereby making the suctioning redundant and useless as the meconium may already be deep within the lungs at the time of birth.[17] Historically, amnioinfusion has been used when MSAF was present, which involves a transcervical infusion of fluid during labour. The idea was to dilute the thick meconium to reduce its potential pathophysiology and reduce cases of MAS, since MAS is more prevalent in cases of thick meconium.[2] However, there are associated risks, such as umbilical cord prolapse and prolongation of labour. The UK National Institute of Health and Clinical Excellence (NICE) Guidelines recommend against the use of amnioinfusion in women with MSAF.[18] ## Prevalence[edit] 1 in every 7 pregnancies have MSAF and, of these cases, approximately 5% of these infants develop MAS.[1] MSAF is observed 23-52% in pregnancies at 42 weeks therefore, the frequency of MAS increases as the length of gestation increases, such that the prevalence is greatest in post-term pregnancies. Conversely, preterm births are not frequently associated with MSAF (only approximately 5% in total contain MSAF). The rate of MAS declines in populations where labour is induced in women that have pregnancies exceeding 41 weeks.[4] There are many suspected pre-disposing factors that are thought to increase the risk of MAS. For example, the risk of MSAF is higher in African American, African and Pacific Islander mothers, compared to mothers from other ethnic groups.[27][6] ## Future research[edit] Research is being focused on developing both a successful method for preventing MAS as well as an effective treatment. For example, investigations are being made in the efficiency of anti-inflammatory agents, surfactant replacement therapy and antibiotic therapy. More research needs to be conducted on the pharmacological properties of, for example, glucocorticoids, including dosages, administration, timing or any drug interactions.[22] Additionally, there is still research being conducted on whether intubation and suctioning of meconium in newborns with MAS is beneficial, harmful or is simply a redundant and outdated treatment. In general, there is still no generally accepted therapeutic protocol and effective treatment plan for MAS. ## See also[edit] * Medicine portal * Aspiration pneumonia ## References[edit] 1. ^ a b c d e f g h i j Van Ierland, Y; De Beaufort, AJ (2009). "Why Does Meconium Cause Meconium Aspiration Syndrome? Current Concepts of MAS Pathophysiology". Early Human Development. 85: 617–620. doi:10.1016/j.earlhumdev.2009.09.009. 2. ^ a b c d e f g h i Vain, NE; Batton, DG (2017). "Meconium "Aspiration" (or Respiratory Distress Associated with Meconium-Stained Amniotic Fluid?)". Seminars in Foetal and Neonatal Medicine. 22: 214–219. doi:10.1016/j.siny.2017.04.002. 3. ^ a b c d e f Rahman, S; Unsworth, J; Vause, S (2013). "Meconium in Labour". Obstetrics, Gynaecology and Reproductive Medicine. 23 (8): 247–252. doi:10.1016/j.ogrm.2013.05.007. 4. ^ a b Argyridis, S; Arulkumaran, S (2016). "Meconium Stained Amniotic Fluid". Obstetrics, Gynaecology and Reproductive Medicine. 26 (8): 227–230. doi:10.1016/j.ogrm.2016.05.001. 5. ^ a b c d Lindenskov, PHH; Castellheim, A; Saugstad, OD (2015). "Meconium Aspiration Syndrome: Possible Pathophysiological Mechanisms and Future Potential Therapies". Neonatology. 107: 225–230. doi:10.1159/000369373. 6. ^ a b c d Swarnam, K; Soraisham, AS; Sivanandan, S (2012). "Advances in the Management of Meconium Aspiration Syndrome". International Journal of Pediatrics. 2012: 1–7. doi:10.1155/2012/359571. PMC 3228378. PMID 22164183. 7. ^ a b Fanaroff, AA (2008). "Meconium Aspiration Syndrome: Historical Aspects". Journal of Perinatology. 28: S3–S7. doi:10.1038/jp.2008.162. 8. ^ Poggi, SH; Ghidini, A (2009). "Pathophysiology of Meconium Passage into the Amniotic Fluid". Early Human Development. 85: 607–610. doi:10.1016/j.earlhumdev.2009.09.011. 9. ^ Beligere, N; Rao, R (2008). "Neurodevelopmental Outcome of Infants with Meconium Aspiration Syndrome: Report of a Study and Literature Review". Journal of Perinatology. 28: S93–S101. doi:10.1038/jp.2008.154. 10. ^ a b Mokra, D; Calkovska, A (2013). "How to Overcome Surfactant Dysfunction in Meconium Aspiration Syndrome". Respiratory Physiology and Neurobiology. 187: 58–63. doi:10.1016/j.resp.2013.02.030. 11. ^ a b c d e f g h i Mokra, D; Mokry, J; Tonhajzerova, I (2013). "Anti-Inflammatory Treatment of Meconium Aspiration Syndrome: Benefits and Risks". Respiratory Physiology and Neurobiology. 187: 52–57. doi:10.1016/j.resp.2013.02.025. 12. ^ Romero, R; Yoon, BH; Chaemsaithong, P; Cortez, J; Park, CW; Behnke, RGE; Hassan, SS; Chaiworapongsa, T; Yeo, L (2014). "Bacteria and Endotoxin in Meconium-Stained Amniotic Fluid at Term: Could Intra-amniotic Infection Cause Meconium Passage?". The Journal of Maternal-Fetal and Neonatal Medicine. 27 (8): 775–788. doi:10.3109/14767058.2013.844124. PMC 5881914. PMID 24028637. 13. ^ Dargaville, PA; Mills, JF (2005). "Surfactant therapy for meconium aspiration syndrome: current status". Drugs. 65 (18): 2569–2591. doi:10.2165/00003495-200565180-00003. 14. ^ Brooke-Vincent, F (2015). "Meconium Aspiration Syndrome and Persistent Pulmonary Hypertension of the Newborn". Journal of Neonatal Nursing. 21: 161–167. doi:10.1016/j.jnn.2015.05.002. 15. ^ Zagariya, A; Bhat, R; Chari, G; Uhal, B; Navale, S; Vidyasagar, D (2005). "Apoptosis of Airway Epithelial Cells in Response to Meconium". Life Sciences. 76: 1849–1858. doi:10.1016/j.lfs.2004.10.033. 16. ^ Marco, P; Nadya, Y; Roselyne, B; Paolo, M; Mostafa, M; De Luca, D (2014). "Lung Ultrasound Findings in Meconium Aspiration Syndrome". Early Human Development. 90 (2): 41–43. doi:10.1016/S0378-3782(14)50011-4. 17. ^ a b c d e Chettri, S; Bhat, BV; Adhisivam, B (2016). "Current Concepts in the Management of Meconium Aspiration Syndrome". Indian J Paediatr. 83 (10): 1125–1130. doi:10.1007/s12098-016-2128-9. 18. ^ a b c Stenson, BJ; Smith, CL (2012). "Management of Meconium Aspiration Syndrome". Paediatrics and Child Health. 22 (12): 532–535. doi:10.1016/j.paed.2012.08.015. 19. ^ a b Aguilar, AM; Vain, NE (2011). "The Suctioning in the Delivery Room Debate". Early Human Development. 87S: S13–S15. doi:10.1016/j.earlhumdev.2011.01.003. 20. ^ Vain, NE; Szyld, EG; Prudent, LM; Wiswell, TE; Aguilar, AM; Vivas, NI (2004). "Oropharyngeal and Nasopharyngeal Suctioning of Meconium-Stained Neonates Before Delivery of their Shoulders: Multicentre, Randomised Controlled Trial". Lancet. 364: 597–602. doi:10.1016/S0140-6736(04)16852-9. 21. ^ Short, BL (2008). "Extracorporeal Membrane Oxygenation: Use in Meconium Aspiration Syndrome". Journal of Perinatology. 28: S79–S83. doi:10.1038/jp.2008.152. PMID 19057615. 22. ^ a b c d Mokra, D; Mokry, J (2011). "Glucocorticoids in the Treatment of Neonatal Meconium Aspiration Syndrome". Eur J Pediatr. 170: 1495–1505. doi:10.1007/s00431-011-1453-2. PMC 3221844. PMID 21465122. 23. ^ a b Czock, D; Keller, F; Rasche, FM; Haussler, U (2005). "Pharmacokinetics and Pharmacodynamics of Systemically Administered Glucocorticoids". Clinical Pharmacokinetics. 44 (1): 61–98. doi:10.2165/00003088-200544010-00003. PMID 15634032. 24. ^ Bassler, D; Choong, K; McNamara, P; Kirpalani, H (2006). "Neonatal Persistent Pulmonary Hypertension Treated with Milrinone: Four Case Report". Biology of the Neonate. 89: 1–5. doi:10.1159/000088192. 25. ^ Choi, HJ; Hahn, S; Lee, J; Park, BJ; Lee, SM; Kin, HS; Bae, CW (2012). "Surfactant Lavage Therapy for Meconium Aspiration Syndrome: A Systematic Review and Meta-Analysis". Neonatology. 101 (3): 183–191. doi:10.1159/000329822. 26. ^ Carson, BS; Losey, RW; Bowes Jr, WA; Simmons, MA (1976). "Combined Obstetric and Pediatric Approach to Prevent Meconium Aspiration Syndrome". Am J Obstet Gynecol. 15 (126): 172–175. doi:10.1016/0002-9378(76)90525-1. 27. ^ Sehaghatian, MR; Othman, I; Hossain, MM; Vidyasagar, D (2000). "Risk of Meconium-Stained Amniotic Fluid in Different Ethnic Groups". J Perinatol. 20: 257–261. doi:10.1038/sj.jp.7200367. ## External links[edit] * eMedicine's article about meconium aspiration syndrome Classification D * ICD-10: P24.0 * ICD-9-CM: 770.11, 770.12 * MeSH: D008471 * DiseasesDB: 7907 External resources * MedlinePlus: 001596 * eMedicine: ped/768 * Orphanet: 70588 * v * t * e Conditions originating in the perinatal period / fetal disease Maternal factors complicating pregnancy, labour or delivery placenta * Placenta praevia * Placental insufficiency * Twin-to-twin transfusion syndrome chorion/amnion * Chorioamnionitis umbilical cord * Umbilical cord prolapse * Nuchal cord * Single umbilical artery presentation * Breech birth * Asynclitism * Shoulder presentation Growth * Small for gestational age / Large for gestational age * Preterm birth / Postterm pregnancy * Intrauterine growth restriction Birth trauma * scalp * Cephalohematoma * Chignon * Caput succedaneum * Subgaleal hemorrhage * Brachial plexus injury * Erb's palsy * Klumpke paralysis Affected systems Respiratory * Intrauterine hypoxia * Infant respiratory distress syndrome * Transient tachypnea of the newborn * Meconium aspiration syndrome * Pleural disease * Pneumothorax * Pneumomediastinum * Wilson–Mikity syndrome * Bronchopulmonary dysplasia Cardiovascular * Pneumopericardium * Persistent fetal circulation Bleeding and hematologic disease * Vitamin K deficiency bleeding * HDN * ABO * Anti-Kell * Rh c * Rh D * Rh E * Hydrops fetalis * Hyperbilirubinemia * Kernicterus * Neonatal jaundice * Velamentous cord insertion * Intraventricular hemorrhage * Germinal matrix hemorrhage * Anemia of prematurity Gastrointestinal * Ileus * Necrotizing enterocolitis * Meconium peritonitis Integument and thermoregulation * Erythema toxicum * Sclerema neonatorum Nervous system * Perinatal asphyxia * Periventricular leukomalacia Musculoskeletal * Gray baby syndrome * muscle tone * Congenital hypertonia * Congenital hypotonia Infections * Vertically transmitted infection * Neonatal infection * rubella * herpes simplex * mycoplasma hominis * ureaplasma urealyticum * Omphalitis * Neonatal sepsis * Group B streptococcal infection * Neonatal conjunctivitis Other * Miscarriage * Perinatal mortality * Stillbirth * Infant mortality * Neonatal withdrawal [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Meconium aspiration syndrome	c0025048	29,847	wikipedia	https://en.wikipedia.org/wiki/Meconium_aspiration_syndrome	2021-01-18T18:40:02	{"gard": ["10494"], "mesh": ["D008471"], "umls": ["C0025048"], "icd-9": ["770.12", "770.11"], "orphanet": ["70588"], "wikidata": ["Q1918881"]}
This article is about the disease. For the protein, see Retinoblastoma protein. Retinoblastoma Rb tumors taken with a retinoscan before and during chemotherapy SpecialtyOncology Retinoblastoma (Rb) is a rare form of cancer that rapidly develops from the immature cells of a retina, the light-detecting tissue of the eye. It is the most common primary malignant intraocular cancer in children, and it is almost exclusively found in young children.[1] Though most children survive this cancer, they may lose their vision in the affected eye(s) or need to have the eye removed. Almost half of children with retinoblastoma have a hereditary genetic defect associated with retinoblastoma. In other cases, it is caused by a congenital mutation in the chromosome 13 gene 13q14 (retinoblastoma protein).[2] ## Contents * 1 Signs and symptoms * 2 Cause * 2.1 RB1 * 2.2 MYCN * 3 Diagnosis * 3.1 Classification * 3.2 Differential diagnosis * 3.3 Morphology * 3.4 Genetic testing * 3.5 Imaging * 4 Treatment * 5 Prognosis * 6 Epidemiology * 7 See also * 8 References * 9 External links ## Signs and symptoms[edit] Leukocoria in a child with retinoblastoma Crossed eyes in a child with retinoblastoma The most common and obvious sign of retinoblastoma is an abnormal appearance of the retina as viewed through the pupil, the medical term for which is leukocoria, also known as amaurotic cat's eye reflex.[1] Other signs and symptoms include deterioration of vision, a red and irritated eye with glaucoma, and faltering growth or delayed development. Some children with retinoblastoma can develop a squint,[3] commonly referred to as "cross-eyed" or "wall-eyed" (strabismus). Retinoblastoma presents with advanced disease in developing countries and eye enlargement is a common finding. Depending on the position of the tumors, they may be visible during a simple eye exam using an ophthalmoscope to look through the pupil. A positive diagnosis is usually made only with an examination under anesthetic (EUA). A white eye reflection is not always a positive indication of retinoblastoma and can be caused by light being reflected badly or by other conditions such as Coats' disease. The presence of the photographic fault red eye in only one eye and not in the other may be a sign of retinoblastoma. A clearer sign is "white eye" or "cat's eye" (leukocoria).[4] ## Cause[edit] Mutation of genes, found in chromosomes, can affect the way in which cells grow and develop within the body.[5] Alterations in RB1 or MYCN can give rise to retinoblastoma. ### RB1[edit] In children with the heritable genetic form of retinoblastoma, a mutation occurs in the RB1 gene on chromosome 13. RB1 was the first tumor suppressor gene cloned.[5] Although RB1 interacts with over 100 cell proteins,[5] its negative regulator effect on the cell cycle principally arises from binding and inactivation of the transcription factor E2F, thus repressing the transcription of genes which are required for the S phase.[5] The defective RB1 gene can be inherited from either parent; in some children, however, the mutation occurs in the early stages of fetal development. The expression of the RB1 allele is autosomal dominant with 90% penetrance. Inherited forms of retinoblastomas are more likely to be bilateral. In addition, inherited uni- or bilateral retinoblastomas may be associated with pineoblastoma and other malignant midline supratentorial primitive neuroectodermal tumors (PNETs) with a dismal outcome; retinoblastoma concurrent with a PNET is known as trilateral retinoblastoma.[6] A recent meta-analysis has shown that survival of trilateral retinoblastoma has increased substantially over the last decades.[7] The development of retinoblastoma can be explained by the two-hit model. According to the two-hit model, both alleles need to be affected, so two events are necessary for the retinal cell or cells to develop into tumors. The first mutational event can be inherited (germline or constitutional), which will then be present in all cells in the body. The second “hit” results in the loss of the remaining normal allele (gene) and occurs within a particular retinal cell.[8] In the sporadic, nonheritable form of retinoblastoma, both mutational events occur within a single retinal cell after fertilization (somatic events); sporadic retinoblastoma tends to be unilateral. Several methods have been developed to detect the RB1 gene mutations.[9][10] Attempts to correlate gene mutations to the stage at presentation have not shown convincing evidence of a correlation.[11] ### MYCN[edit] Not all retinoblastoma cases are with RB1 inactivation. There are cases reported with only one RB1 mutation or even two functional RB1 alleles, which indicates other oncogenic lesions of retinoblastoma.[12] Somatic amplification of the MYCN oncogene is responsible for some cases of nonhereditary, early-onset, aggressive, unilateral retinoblastoma. MYCN can act as a transcription factor and promotes proliferation by regulating the expression of cell cycle genes.[13][14] Although MYCN amplification accounted for only 1.4% of retinoblastoma cases, researchers identified it in 18% of infants diagnosed at less than 6 months of age. Median age at diagnosis for MYCN retinoblastoma was 4.5 months, compared with 24 months for those who had nonfamilial unilateral disease with two RB1 gene mutations.[15] ## Diagnosis[edit] Screening for retinoblastoma should be part of a "well baby" screening for newborns during the first 3 months of life, to include: * The red reflex: checking for a normal reddish-orange reflection from the eye's retina with an ophthalmoscope or retinoscope from about 30 cm or 1 foot, usually done in a dimly lit or dark room * The corneal light reflex or Hirschberg test: checking for symmetrical reflection of beam of light in the same spot on each eye when a light is shined into each cornea, to help determine whether the eyes are crossed * Eye examination: checking for any structural abnormalities ### Classification[edit] The two forms of the disease are a heritable form and nonheritable form (all cancers are considered genetic in that mutations of the genome are required for their development, but this does not imply that they are heritable, or transmitted to offspring). Around 55% of children with retinoblastoma have the nonheritable form. If no history of the disease exists within the family, the disease is labeled "sporadic", but this does not necessarily indicate that it is the nonheritable form. Bilateral retinoblastomas are commonly heritable, while unilateral retinoblastomas are commonly nonheritable. In about two-thirds of cases,[16] only one eye is affected (unilateral retinoblastoma); in the other third, tumors develop in both eyes (bilateral retinoblastoma). The number and size of tumors on each eye may vary. In certain cases, the pineal gland or the suprasellar or parasellar region (or in very rare cases other midline intracranial locations) is also affected (trilateral retinoblastoma). The position, size, and quantity of tumors are considered when choosing the type of treatment for the disease. ### Differential diagnosis[edit] 1\. Persistent hyperplastic primary vitreous is a congenital developmental anomaly of the eye resulting from failure of the embryological, primary vitreous, and hyaloid vasculature to regress, whereby the eye is shorter, develops a cataract, and may present with whitening of the pupil. 2\. Coats disease is a typically unilateral disease characterised by abnormal development of blood vessels behind the retina, leading to blood vessel abnormalities in the retina and retinal detachment to mimic retinoblastoma. 3\. Toxocariasis is a parasitic disease of the eye associated with exposure to infected puppies, which causes a retinal lesion leading to retinal detachment. 4\. Retinopathy of prematurity is associated with low-birth-weight infants who receive supplemental oxygen in the period immediately after birth, and it involves damage to the retinal tissue and may lead to retinal detachment. MRI pattern of retinoblastoma with optic nerve involvement (sagittal enhanced T1-weighted sequence) If the eye examination is abnormal, further testing may include imaging studies, such as computerized tomography (CT), magnetic resonance imaging (MRI), and ultrasound.[17] CT and MRI can help define the structure abnormalities and reveal any calcium depositions. Ultrasound can help define the height and thickness of the tumor. Bone marrow examination or lumbar puncture may also be done to determine any metastases to bones or the brain. ### Morphology[edit] Gross and microscopic appearances of retinoblastoma are identical in both hereditary and sporadic types. Macroscopically, viable tumor cells are found near blood vessels, while zones of necrosis are found in relatively avascular areas. Microscopically, both undifferentiated and differentiated elements may be present. Undifferentiated elements appear as collections of small, round cells with hyperchromatic nuclei; differentiated elements include Flexner-Wintersteiner rosettes, Homer Wright rosettes,[18] and fleurettes from photoreceptor differentiation.[19] * Drawing of a large retinoblastoma * Aspect of trilateral retinoblastoma on MRI * An ocular ultrasound of a large retinoblastoma tumor within the eye of a 3-year-old boy * Funduscopic finding of a retinoblastoma * Ocular fundus aspect of retinoblastoma * Gross pathology of retinoblastoma tumor in enucleated eye of 3-year-old female * Large exophytic white tumor with foci of calcification producing total exudative retinal detachment * Flexner-Wintersteiner rosettes in retinoblastoma * Retinoblastoma, 400 X magnification * Crystal structure of the retinoblastoma tumor suppressor protein bound to E2F peptide polymer ### Genetic testing[edit] Identifying the RB1 gene mutation that led to a child's retinoblastoma can be important in the clinical care of the affected individual and in the care of (future) siblings and offspring. It may run in the family. 1. Bilaterally affected individuals and 13-15% of unilaterally affected individuals,[20][21] are expected to show an RB1 mutation in blood. By identifying the RB1 mutation in the affected individual, (future) siblings, children, and other relatives can be tested for the mutation; if they do not carry the mutation, child relatives are not at risk of retinoblastoma, so need not undergo the trauma and expense of examinations under anaesthetic.[22] For the 85% of unilaterally affected patients found not to carry either of their eye tumor RB1 mutations in blood, neither molecular testing nor clinical surveillance of siblings is required. 2. If the RB1 mutation of an affected individual is identified, amniotic cells in an at-risk pregnancy can be tested for the family mutation; any fetus that carries the mutation can be delivered early, allowing early treatment of any eye tumors, leading to better visual outcomes.[22] 3. For cases of unilateral retinoblastoma where no eye tumor is available for testing, if no RB1 mutation is detected in blood after high-sensitivity molecular testing (i.e. >93% RB1 mutation detection sensitivity), the risk of a germline RB1 mutation is reduced to less than 1%,[21] a level at which only clinic examination (and not examinations under anaesthetic) is recommended for the affected individual and their future offspring (National Retinoblastoma Strategy, Canadian Guidelines for Care).[23] ### Imaging[edit] Traditional ultrasound B scan can detect calcifications in the tumour while high-frequency ultrasound B scan is able to provide higher resolution than the traditional ultrasound and determine the proximity of the tumour with front portion of the eye. MRI scan can detect high-risk features such as optic nerve invasion; choroidal invasion, scleral invasion, and intracranial invasion. CT scan is generally avoided because radiation can stimulate the formation of more eye tumours in those with RB1 genetic mutation.[24] ## Treatment[edit] Historical image showing Gordon Isaacs, the first patient treated with the linear accelerator (external beam radiation therapy) for retinoblastoma, in 1957. Gordon's right eye was removed January 11, 1957 because the cancer had spread. His left eye, however, had only a localized tumor that prompted Henry Kaplan to try to treat it with the electron beam. The priority of retinoblastoma treatment is to preserve the life of the child, then to preserve vision, and then to minimize complications or side effects of treatment. The exact course of treatment depends on the individual case and is decided by the ophthalmologist in discussion with the paediatric oncologist.[25] Correct treatment also depends on the mutation type, whether it is a germline RB1 mutation, a sporadic RB1 mutation or MYCN amplification with functional RB1.[26] Children with involvement of both eyes at diagnosis usually require multimodality therapy (chemotherapy, local therapies). The various treatment modalities for retinoblastoma includes:[25] * Enucleation of the eye – Most patients with unilateral disease present with advanced intraocular disease, so usually undergo enucleation, which results in a cure rate of 95%. In bilateral Rb, enucleation is usually reserved for eyes that have failed all known effective therapies or without useful vision. * External beam radiotherapy (EBR) – The most common indication for EBR is for the eye in a young child with bilateral retinoblastoma who has active or recurrent disease after completion of chemotherapy and local therapies. However, patients with hereditary disease who received EBR therapy are reported to have a 35% risk of second cancers.[27] * Brachytherapy involves the placement of a radioactive implant (plaque), usually on the sclera adjacent to the base of a tumor. It used as the primary treatment, or more frequently, in patients with small tumors or in those who had failed initial therapy including previous EBR therapy. * Thermotherapy involves the application of heat directly to the tumor, usually in the form of infrared radiation. It is also used for small tumors. * Laser photocoagulation is recommended only for small posterior tumors. An argon or diode laser or a xenon arc is used to coagulate all the blood supply to the tumor. * Cryotherapy induces damage to the vascular endothelium with secondary thrombosis and infarction of the tumor tissue by rapidly freezing it. It may be used as primary therapy for small peripheral tumors or for small recurrent tumors previously treated with other methods. * Systemic chemotherapy has become forefront of treatment in the past decade, in the search for globe-preserving measures and to avoid the adverse effects of EBR therapy. The common indications for chemotherapy for intraocular retinoblastoma include tumors that are large and that cannot be treated with local therapies alone in children with bilateral tumors. It is also used in patients with unilateral disease when the tumors are small, but cannot be controlled with local therapies alone. * Intra-arterial chemotherapy – Chemotherapeutic drugs are administered locally by a thin catheter threaded through the groin, through the aorta, and the neck, directly into the optic vessels.[28] * Nanoparticulate chemotherapy – To reduce the adverse effects of systemic therapy, subconjuctival (local) injection of nanoparticle carriers containing chemotherapeutic agents (carboplatin) has been developed, which has shown promising results in the treatment of retinoblastoma in animal models without adverse effects.[29][30] * Chemoreduction is a combined approach using chemotherapy to initially reduce the size of the tumor, and adjuvant focal treatments, such as transpupillary thermotherapy, to control the tumor.[31][32] ## Prognosis[edit] In the developed world, retinoblastoma has one of the best cure rates of all childhood cancers (95-98%), with more than 90% of sufferers surviving into adulthood. In the UK, around 40 to 50 new cases are diagnosed each year. Good prognosis depends upon early presentation of the child in health facility.[33][34] Late presentation is associated with a poor prognosis.[35] Survivors of hereditary retinoblastoma have a higher risk of developing other cancers later in life. ## Epidemiology[edit] Retinoblastoma presents with cumulative lifetime incidence rate of one case of retinoblastoma per 18000 to 30000 live births worldwide.[36] A higher incidence is noted in developing countries, which has been attributed to lower socioeconomic status and the presence of human papilloma virus sequences in the retinoblastoma tissue.[37] Almost 80% of children with retinoblastoma are diagnosed before three years of age and diagnosis in children above six years of age is extremely rare.[38] In the UK, bilateral cases usually present within 14 to 16 months, while diagnosis of unilateral cases peaks between 24 and 30 months. ## See also[edit] * Eye cancer * Eye examination * Retinoblastoma protein ## References[edit] 1. ^ a b American Cancer Society (2003). "Chapter 85. Neoplasms of the Eye". Cancer Medicine. Hamilton, Ontario: BC Decker Inc. ISBN 978-1-55009-213-4. 2. ^ Ryan, Stephen J.; Schachat, Andrew P.; Wilkinson, Charles P.; Hinton, David R.; Sadda, SriniVas R.; Wiedemann, Peter (2012-11-01). Retina. Elsevier Health Sciences. p. 2105. ISBN 978-1455737802. 3. ^ A. R. Elkington; P. T. Khaw (1988). "ABC of eyes. Squint". BMJ. 297 (6648): 608–611. doi:10.1136/bmj.297.6648.608. PMC 1834556. PMID 3139234. 4. ^ Introduction to White Eye Archived 2011-04-26 at the Wayback Machine, Daisy's Eye Cancer Fund. 5. ^ a b c d Du W, Pogoriler J (August 2006). "Retinoblastoma family genes". Oncogene. 25 (38): 5190–200. doi:10.1038/sj.onc.1209651. PMC 1899835. PMID 16936737. 6. ^ Kivelä T (June 1999). "Trilateral retinoblastoma: a meta-analysis of hereditary retinoblastoma associated with primary ectopic intracranial retinoblastoma". Journal of Clinical Oncology. 17 (6): 1829–37. doi:10.1200/JCO.1999.17.6.1829. PMID 10561222. 7. ^ de Jong MC, et al. (August 2014). "Trilateral retinoblastoma: a systematic review and meta-analysis". The Lancet Oncology. 15 (10): 1157–1167. doi:10.1016/s1470-2045(14)70336-5. PMID 25126964. 8. ^ Harbour J.W., Dean D.C. Rb function in cell-cycle regulation and apoptosis" Nature Cell Biology. 2000;94:E65–E67. 9. ^ Parsam VL, Kannabiran C, Honavar S, et al. (December 2009). "A comprehensive, sensitive and economical approach for the detection of mutations in the RB1 gene in retinoblastoma". Journal of Genetics. 88 (4): 517–27. doi:10.1007/s12041-009-0069-z. PMID 20090211. S2CID 10723496. 10. ^ Lohmann DR, Gallie BL (2010). "Retinoblastoma". GeneReviews. Seattle, WA: University of Washington. PMID 20301625. 11. ^ Parsam Ali MJ, Parsam VL, Honavar SG, et al. (2010). "RB1 gene mutations in retinoblastoma and its clinical correlation". Saudi Journal of Ophthalmology. 24 (4): 119–123. doi:10.1016/j.sjopt.2010.05.003. PMC 3729507. PMID 23960888. 12. ^ Rushlow, Diane E; Mol, Berber M; Kennett, Jennifer Y; Yee, Stephanie; Pajovic, Sanja; Thériault, Brigitte L; Prigoda-Lee, Nadia L; Spencer, Clarellen; Dimaras, Helen; Corson, Timothy W; Pang, Renée (April 2013). "Characterisation of retinoblastomas without RB1 mutations: genomic, gene expression, and clinical studies". The Lancet Oncology. 14 (4): 327–334. doi:10.1016/S1470-2045(13)70045-7. PMID 23498719. 13. ^ Woo, Chan-Wook; Tan, Fei; Cassano, Hope; Lee, JungHwa; Lee, Kwang Chul; Thiele, Carol J. (February 2008). "Use of RNA interference to elucidate the effect of MYCN on cell cycle in neuroblastoma". Pediatric Blood & Cancer. 50 (2): 208–212. doi:10.1002/pbc.21195. PMID 17420990. S2CID 22765085. 14. ^ Stenfelt, Sonya; Blixt, Maria K. E.; All‐Ericsson, Charlotta; Hallböök, Finn; Boije, Henrik (December 2017). "Heterogeneity in retinoblastoma: a tale of molecules and models". Clinical and Translational Medicine. 6 (1). doi:10.1186/s40169-017-0173-2. ISSN 2001-1326. PMC 5680409. PMID 29124525. 15. ^ Lewis R (March 19, 2013). "Some Aggressive Retinoblastomas Lack RB1 Mutations". Medscape Online. Archived from the original on September 19, 2017. 16. ^ MacCarthy A, Birch JM, Draper GJ, et al. (January 2009). "Retinoblastoma in Great Britain 1963-2002". British Journal of Ophthalmology. 93 (1): 33–7. doi:10.1136/bjo.2008.139618. PMID 18838413. S2CID 27049728. 17. ^ de Jong MC, de Graaf P, Noij DP, Göricke S, Maeder P, Galluzzi P, Brisse HJ, Moll AC, Castelijns JA (May 2014). "Diagnostic performance of magnetic resonance imaging and computed tomography for advanced retinoblastoma: a systematic review and meta-analysis". Ophthalmology. 121 (5): 1109–18. doi:10.1016/j.ophtha.2013.11.021. PMID 24589388. 18. ^ Lee, K. Weng Sehu,... William R. (2005). Ophthalmic pathology : an illustrated guide for clinicians. Malden: Blackwell Publishing. p. 262. ISBN 978-0-7279-1779-9. 19. ^ Kumar V, Abbas AK, Fausto N. Robbins and Cotran Pathologic Basis of Disease. Seventh Edition. Philadelphia: Elsevier Saunders, 2005, p. 1442. 20. ^ Schüler A, Weber S, Neuhäuser M, et al. (March 2005). "Age at diagnosis of isolated unilateral retinoblastoma does not distinguish patients with and without a constitutional RB1 gene mutation but is influenced by a parent-of-origin effect". European Journal of Cancer. 41 (5): 735–40. doi:10.1016/j.ejca.2004.12.022. PMID 15763650. 21. ^ a b Rushlow D, Piovesan B, Zhang K, et al. (May 2009). "Detection of mosaic RB1 mutations in families with retinoblastoma". Human Mutation. 30 (5): 842–51. doi:10.1002/humu.20940. PMID 19280657. S2CID 31887184. 22. ^ a b Richter S, Vandezande K, Chen N, et al. (December 2002). "Sensitive and efficient detection of RB1 gene mutations enhances care for families with retinoblastoma". American Journal of Human Genetics. 72 (2): 253–69. doi:10.1086/345651. PMC 379221. PMID 12541220. 23. ^ Canadian Ophthalmological Society' (December 2009). "National Retinoblastoma Strategy Canadian Guidelines for Care; Genetic Analysis" (PDF). Canadian Journal of Ophthalmology. 44 (suppl.2): S17–S22. doi:10.3129/i09-194. PMID 20237571. Archived from the original (PDF) on 2011-09-29. 24. ^ Dimaras, Helen; Corson, Timothy W. (January 2019). "Retinoblastoma, the visible CNS tumor: A review: DIMARAS and CORSON". Journal of Neuroscience Research. 97 (1): 29–44. doi:10.1002/jnr.24213. PMC 6034991. PMID 29314142. 25. ^ a b Chintagumpala M, Chevez-Barrios P, Paysse EA, Plon SE, Hurwitz R (October 2007). "Retinoblastoma: review of current management". Oncologist. 12 (10): 1237–46. CiteSeerX 10.1.1.585.5448. doi:10.1634/theoncologist.12-10-1237. PMID 17962617. 26. ^ Li, Wenhui L.; Buckley, Jonathan; Sanchez-Lara, Pedro A.; Maglinte, Dennis T.; Viduetsky, Lucy; Tatarinova, Tatiana V.; Aparicio, Jennifer G.; Kim, Jonathan W.; Au, Margaret; Ostrow, Dejerianne; Lee, Thomas C. (July 2016). "A Rapid and Sensitive Next-Generation Sequencing Method to Detect RB1 Mutations Improves Care for Retinoblastoma Patients and Their Families". The Journal of Molecular Diagnostics. 18 (4): 480–493. doi:10.1016/j.jmoldx.2016.02.006. PMC 5820122. PMID 27155049. 27. ^ Roarty JD, McLean IW, Zimmerman LE (November 1988). "Incidence of second neoplasms in patients with bilateral retinoblastoma". Ophthalmology. 95 (11): 1583–1587. doi:10.1016/s0161-6420(88)32971-4. PMID 3211467. 28. ^ Shields, CL; Ramasubramanian, A; Rosenwasser, R; Shields, JA (September 2009). "Superselective catheterization of the ophthalmic artery for intraarterial chemotherapy for retinoblastoma". Retina (Philadelphia, Pa.). 29 (8): 1207–9. doi:10.1097/IAE.0b013e3181b4ce39. PMID 19734768. 29. ^ Shome D, Poddar N, Sharma V, et al. (2009). "Does a Nanomolecule of Carboplatin Injected Periocularly Help in Attaining Higher Intravitreal Concentrations?". Investigative Ophthalmology and Visual Science. 50 (12): 5896–900. doi:10.1167/iovs.09-3914. PMID 19628744. S2CID 7361361. 30. ^ Kang SJ, Durairaj C, Kompella UB, et al. (2009). "Subconjunctival nanoparticle carboplatin in the treatment of murine retinoblastoma". Archives of Ophthalmology. 127 (8): 1043–7. doi:10.1001/archophthalmol.2009.185. PMC 2726977. PMID 19667343. 31. ^ Fabian ID, Johnson KP, Stacey AW, Sagoo MS, Reddy MA (June 2017). "Focal laser treatment in addition to chemotherapy for retinoblastoma". Cochrane Database Syst Rev. 6: CD012366. doi:10.1002/14651858.CD012366.pub2. PMC 6481366. PMID 28589646. 32. ^ Shields CL, Mashayekhi A, Cater J, Shelil A, Ness S, Meadows AT, Shields JA (June 2005). "Macular retinoblastoma managed with chemoreduction: analysis of tumor control with or without adjuvant thermotherapy in 68 tumors". Arch. Ophthalmol. 123 (6): 765–73. doi:10.1001/archopht.123.6.765. PMID 15955977. 33. ^ Syed Imtiaz Ali Shah: Concise Ophthalmology. 4th ed. Paramount B (Pvt.) Ltd. 2014: 80-81 34. ^ "Paramount Books Online Bookstore 9789696370017 : Concise-Ophthalmology-(pb)-2014". Archived from the original on 2014-07-30. Retrieved 2014-08-09. 35. ^ Partab Rai, Imtiaz Ali Shah, Ashok Kumar Nasrani, Mahesh Kumar Lohana, Muhammad Khan Memon, Manzoor Ahmed Memon: Too late presentation of 53 patients with retinoblastoma:a big challenge: International Journal of Ophthalmology 2009, vol. 9, no. 2; pp. 227-230. 36. ^ Abramson D.H.; Schefler A.C. (2004). "Update on retinoblastoma". Retina. 24 (6): 828–48. doi:10.1097/00006982-200412000-00002. PMID 15579980. S2CID 26883037. 37. ^ Orjuela M, Castaneda VP, Ridaura C, et al. (2000). "Presence of human papilloma virus in tumor tissue from children with retinoblastoma: An alternative mechanism for tumor development". Clinical Cancer Research. 6 (10): 4010–4016. PMID 11051250. 38. ^ Abramson DH, Frank CM, Susman M, et al. (1998). "Presenting signs of retinoblastoma". Journal of Pediatrics. 132 (3): 505–508. doi:10.1016/s0022-3476(98)70028-9. PMID 9544909. ## External links[edit] * Retinoblastoma information from MedlinePlus * retinoblastoma at NIH/UW GeneTests * RB1 Mutation Database * Retinoblastoma at Curlie * NCBI Genetic Testing Registry Classification D * ICD-10: C69.2 * ICD-9-CM: 190.5 * ICD-O: M9510/3 * OMIM: 180200 * MeSH: D012175 * DiseasesDB: 11434 External resources * MedlinePlus: 001030 * eMedicine: oph/346 * Patient UK: Retinoblastoma * GeneReviews: Retinoblastoma * v * t * e Tumours of the nervous system Endocrine Sellar: * Craniopharyngioma * Pituicytoma Other: * Pinealoma CNS Neuroepithelial (brain tumors, spinal tumors) Glioma Astrocyte * Astrocytoma * Pilocytic astrocytoma * Pleomorphic xanthoastrocytoma * Subependymal giant cell astrocytoma * Fibrillary astrocytoma * Anaplastic astrocytoma * Glioblastoma multiforme Oligodendrocyte * Oligodendroglioma * Anaplastic oligodendroglioma Ependyma * Ependymoma * Subependymoma Choroid plexus * Choroid plexus tumor * Choroid plexus papilloma * Choroid plexus carcinoma Multiple/unknown * Oligoastrocytoma * Gliomatosis cerebri * Gliosarcoma Mature neuron * Ganglioneuroma: Ganglioglioma * Retinoblastoma * Neurocytoma * Dysembryoplastic neuroepithelial tumour * Lhermitte–Duclos disease PNET * Neuroblastoma * Esthesioneuroblastoma * Ganglioneuroblastoma * Medulloblastoma * Atypical teratoid rhabdoid tumor Primitive * Medulloepithelioma Meninges * Meningioma * Hemangiopericytoma Hematopoietic * Primary central nervous system lymphoma PNS: * Nerve sheath tumor * Cranial and paraspinal nerves * Neurofibroma * Neurofibromatosis * Neurilemmoma/Schwannoma * Acoustic neuroma * Malignant peripheral nerve sheath tumor Other * WHO classification of the tumors of the central nervous system Note: Not all brain tumors are of nervous tissue, and not all nervous tissue tumors are in the brain (see brain metastasis). * v * t * e Eye neoplasm Melanoma * Uveal melanoma * Ciliary body melanoma Other * Medulloepithelioma/Diktyoma * Intraocular lymphoma * Orbital lymphoma * Optic nerve sheath meningioma * Optic nerve tumor * Retinoblastoma * Schwannoma * Visual pathway glioma [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Retinoblastoma	c0035335	29,848	wikipedia	https://en.wikipedia.org/wiki/Retinoblastoma	2021-01-18T18:44:11	{"gard": ["7563"], "mesh": ["D012175"], "umls": ["C0035335"], "icd-9": ["190.5"], "icd-10": ["C69.2"], "orphanet": ["790"], "wikidata": ["Q500695"]}
A number sign (#) is used with this entry because of evidence that L-ferritin deficiency (LFTD) is caused by homozygous or heterozygous mutation in the FTL gene (134790) on chromosome 19q13. Two unrelated individuals, 1 homozygous and 1 heterozygous for mutations, have been reported. Clinical Features Cremonesi et al. (2004) found decreased L-ferritin levels in a healthy 52-year-old woman who was a control subject in a genetic study of hyperferritinemia-cataract syndrome (HHCS; 600886). She had no history of iron deficiency anemia or neurologic dysfunction, and hematologic examination was normal except for decreased serum L-ferritin. Cozzi et al. (2013) reported a 23-year-old woman, born of parents from the same region of Calabria, Italy, with complete absence of serum L-ferritin, but otherwise normal hematologic parameters. She developed idiopathic generalized seizures at age 7 years, but the seizures were well-controlled; anticonvulsive therapy was stopped at age 22 years without recurrence. She had mild neuropsychologic impairment, as well as restless legs syndrome demonstrated by polysomnography. The only other notable feature was progressive hair loss. Serum hemoglobin, mean corpuscular volume, haptoglobin, total red blood cells, iron levels, transferrin, and transferrin saturation were all normal. Brain and liver imaging showed no evidence of iron deposition. Molecular Genetics In a healthy 52-year-old woman with low serum L-ferritin, Cremonesi et al. (2004) identified a heterozygous mutation in the ATG start codon of the FTL gene (M1V; 134790.0018), predicted to disable protein translation and expression. The findings suggested that L-ferritin has no effect on systemic iron metabolism and that haploinsufficiency of L-ferritin does not cause neurologic or hematologic clinical effects. In a 23-year-old woman with complete absence of serum L-ferritin, Cozzi et al.(2013) identified a homozygous truncating mutation in the FTL gene (E104X; 134790.0019). The FTL gene was chosen for sequencing because the patient had undetectable serum levels of L-ferritin. There was no FTL protein in patient fibroblasts, although mRNA levels were similar to controls. FTH (134770) expression was normal, and patient cells showed increased iron incorporation into H homopolymer ferritin compared to controls. This was associated with a 4-fold decrease of the labile iron pool in patient cells. Expression of wildtype FTL ameliorated these cellular defects. E104X fibroblasts showed additional abnormalities, including increased turnover of H homopolymer ferritin and increased production of reactive oxygen species and increased cellular toxicity compared to controls. Reprogrammed neurons from patient fibroblasts also showed increased reactive oxygen species as well as iron deficiency. Cozzi et al. (2013) stated that this was the first patient reported with complete loss of FTL, but noted that the phenotype could result either from a loss of FTL function or a gain of function via altered activity of the FTH homopolymer. INHERITANCE \- Autosomal dominant \- Autosomal recessive SKIN, NAILS, & HAIR Hair \- Hair loss, progressive (homozygous patient) NEUROLOGIC Central Nervous System \- Idiopathic generalized epilepsy in childhood (homozygous patient) \- Neurocognitive impairment, mild (homozygous patient) HEMATOLOGY \- Normal hematologic parameters (both patients) LABORATORY ABNORMALITIES \- Undetectable serum L-transferrin (homozygous patient) \- Decreased serum L-transferrin (heterozygous patient) MISCELLANEOUS \- Two unrelated individuals have been reported (last curated January 2014) \- One individual carried a heterozygous mutation, whereas the other carried a homozygous mutation. MOLECULAR BASIS \- Caused by mutation in the ferritin light chain gene (FTL, 134790.0018 ) ▲ 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	L-FERRITIN DEFICIENCY	c3810090	29,849	omim	https://www.omim.org/entry/615604	2019-09-22T15:51:25	{"omim": ["615604"], "orphanet": ["440731"], "synonyms": []}
Popliteal pterygium syndrome Popliteal pterygium syndrome is inherited in an autosomal dominant pattern. SpecialtyMedical genetics Popliteal pterygium syndrome (PPS) is an inherited condition affecting the face, limbs, and genitalia.[1] The syndrome goes by a number of names including the popliteal web syndrome and, more inclusively, the facio-genito-popliteal syndrome. The term PPS was coined by Gorlin et al.. in 1968 on the basis of the most unusual anomaly, the popliteal pterygium (a web behind the knee).[2] ## Contents * 1 Symptoms and signs * 2 Genetics * 2.1 Relationship to Van der Woude syndrome * 3 Diagnosis * 4 Treatment * 5 Epidemiology * 6 See also * 7 References * 8 External links ## Symptoms and signs[edit] Clinical expressions of PPS are highly variable, but include the following:[3][4][5] * Limb findings: an extensive web running from behind the knee down to the heel (90%), malformed toenails, and webbed toes. * Facial findings: cleft palate with or without cleft lip (75%), pits in the lower lip (40%), fibrous bands in the mouth known as syngnathia (25%), and tissue connecting the upper and lower eyelids * Genital findings (50%): hypoplasia of the labia majora, malformation of the scrotum, and cryptorchidism. ## Genetics[edit] The genetic locus for PPS was localized to chromosome 1 in 1999. The disorder is inherited in an autosomal dominant manner and is due to mutation of the IRF6 gene. Most reported cases are sporadic; advanced parental age is found in a number of these cases, suggesting new mutations.[citation needed] The term PPS has also been used for two rare autosomal recessively inherited conditions: Lethal PPS and PPS with Ectodermal Dysplasia. Although both conditions feature a cleft lip/palate, syngnathia, and popliteal pterygium, they are clinically distinguishable from the autosomal dominant case. Lethal PPS is differentiated by microcephaly, corneal aplasia, ectropion, bony fusions, hypoplastic nose and absent thumbs, while PPS with Ectodermal Dysplasia is differentiated by woolly hair, brittle nails, ectodermal anomalies, and fissure of the sacral vertebrae.[6] ### Relationship to Van der Woude syndrome[edit] Van der Woude syndrome (VDWS) and popliteal pterygium syndrome (PPS) are allelic variants of the same condition; that is, they are caused by different mutations of the same gene. PPS includes all the features of VDWS, plus popliteal pterygium, syngnathia, distinct toe/nail abnormality, syndactyly, and genito-urinary malformations.[7] ## Diagnosis[edit] This section is empty. You can help by adding to it. (May 2017) ## Treatment[edit] This section is empty. You can help by adding to it. (May 2017) ## Epidemiology[edit] The diagnosis of PPS has been made in several ethnic groups, including Caucasian, Japanese, and sub-Saharan African. Males and females are equally likely to suffer from the syndrome. Since the disorder is very rare, its incidence rate is difficult to estimate, but is less than 1 in 10,000.[8] ## See also[edit] * List of cutaneous conditions * Multiple pterygium syndrome ## References[edit] 1. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology (10th ed.). Saunders. p. 577. ISBN 978-0-7216-2921-6. 2. ^ Gorlin RJ, Sedano HO, Cervenka J (February 1968). "Popliteal pterygium syndrome . A syndrome comprising cleft lip-palate, popliteal and intercrural pterygia, digital and genital anomalies". Pediatrics. 41 (2): 503–9. PMID 4384166. 3. ^ medterms.com 4. ^ Parikh SN, Crawford AH, Do TT, Roy DR (May 2004). "Popliteal pterygium syndrome: implications for orthopaedic management". J Pediatr Orthop B. 13 (3): 197–201. doi:10.1097/01202412-200405000-00010. PMID 15083121. 5. ^ https://ghr.nlm.nih.gov/condition/popliteal-pterygium-syndrome#Description 6. ^ Cardoso ER, Hawary MB, Mahmud S (April 1998). "A recessively inherited non-lethal form of popliteal pterygium syndrome". Br J Oral Maxillofac Surg. 36 (2): 138–40. doi:10.1016/s0266-4356(98)90183-8. PMID 9643601. 7. ^ Wong FK, Hagg U (October 2004). "An update on the aetiology of orofacial clefts". Hong Kong Med J. 10 (5): 331–6. PMID 15479962. 8. ^ Froster-Iskenius UG (May 1990). "Popliteal pterygium syndrome". J. Med. Genet. 27 (5): 320–6. doi:10.1136/jmg.27.5.320. PMC 1017084. PMID 2352260. ## External links[edit] Classification D * ICD-10: Q79.8 (EUROCAT Q79.82) * ICD-9-CM: 756.89 * OMIM: 119500 * MeSH: C562509 * DiseasesDB: 33503 External resources * Orphanet: 294963 * v * t * e Genetic disorders relating to deficiencies of transcription factor or coregulators (1) Basic domains 1.2 * Feingold syndrome * Saethre–Chotzen syndrome 1.3 * Tietz syndrome (2) Zinc finger DNA-binding domains 2.1 * (Intracellular receptor): Thyroid hormone resistance * Androgen insensitivity syndrome * PAIS * MAIS * CAIS * Kennedy's disease * PHA1AD pseudohypoaldosteronism * Estrogen insensitivity syndrome * X-linked adrenal hypoplasia congenita * MODY 1 * Familial partial lipodystrophy 3 * SF1 XY gonadal dysgenesis 2.2 * Barakat syndrome * Tricho–rhino–phalangeal syndrome 2.3 * Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome * Denys–Drash syndrome * Duane-radial ray syndrome * MODY 7 * MRX 89 * Townes–Brocks syndrome * Acrocallosal syndrome * Myotonic dystrophy 2 2.5 * Autoimmune polyendocrine syndrome type 1 (3) Helix-turn-helix domains 3.1 * ARX * Ohtahara syndrome * Lissencephaly X2 * MNX1 * Currarino syndrome * HOXD13 * SPD1 synpolydactyly * PDX1 * MODY 4 * LMX1B * Nail–patella syndrome * MSX1 * Tooth and nail syndrome * OFC5 * PITX2 * Axenfeld syndrome 1 * POU4F3 * DFNA15 * POU3F4 * DFNX2 * ZEB1 * Posterior polymorphous corneal dystrophy * Fuchs' dystrophy 3 * ZEB2 * Mowat–Wilson syndrome 3.2 * PAX2 * Papillorenal syndrome * PAX3 * Waardenburg syndrome 1&3 * PAX4 * MODY 9 * PAX6 * Gillespie syndrome * Coloboma of optic nerve * PAX8 * Congenital hypothyroidism 2 * PAX9 * STHAG3 3.3 * FOXC1 * Axenfeld syndrome 3 * Iridogoniodysgenesis, dominant type * FOXC2 * Lymphedema–distichiasis syndrome * FOXE1 * Bamforth–Lazarus syndrome * FOXE3 * Anterior segment mesenchymal dysgenesis * FOXF1 * ACD/MPV * FOXI1 * Enlarged vestibular aqueduct * FOXL2 * Premature ovarian failure 3 * FOXP3 * IPEX 3.5 * IRF6 * Van der Woude syndrome * Popliteal pterygium syndrome (4) β-Scaffold factors with minor groove contacts 4.2 * Hyperimmunoglobulin E syndrome 4.3 * Holt–Oram syndrome * Li–Fraumeni syndrome * Ulnar–mammary syndrome 4.7 * Campomelic dysplasia * MODY 3 * MODY 5 * SF1 * SRY XY gonadal dysgenesis * Premature ovarian failure 7 * SOX10 * Waardenburg syndrome 4c * Yemenite deaf-blind hypopigmentation syndrome 4.11 * Cleidocranial dysostosis (0) Other transcription factors 0.6 * Kabuki syndrome Ungrouped * TCF4 * Pitt–Hopkins syndrome * ZFP57 * TNDM1 * TP63 * Rapp–Hodgkin syndrome/Hay–Wells syndrome/Ectrodactyly–ectodermal dysplasia–cleft syndrome 3/Limb–mammary syndrome/OFC8 Transcription coregulators Coactivator: * CREBBP * Rubinstein–Taybi syndrome Corepressor: * HR (Atrichia with papular lesions) [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Popliteal pterygium syndrome	c0265259	29,850	wikipedia	https://en.wikipedia.org/wiki/Popliteal_pterygium_syndrome	2021-01-18T19:02:52	{"gard": ["3242"], "mesh": ["C562509"], "umls": ["C0265259"], "orphanet": ["294963", "1300"], "wikidata": ["Q1587881"]}
A number sign (#) is used with this entry because of evidence that distal hereditary motor neuronopathy type IID (HMN2D) is caused by heterozygous mutation in the FBXO38 gene (608533) on chromosome 5q32. Description Distal hereditary motor neuronopathy type IID is an autosomal dominant neurologic disorder characterized by onset of slowly progressive distal lower limb weakness and atrophy between the second and fourth decades of life. Weakness usually begins in the calf muscles and later involves more proximal muscles. The severity is variable, and some patients have difficulty walking or running. Most also have upper limb involvement, particularly of the triceps and intrinsic hand muscles. Some patients may lose independent ambulation later in the disease course. Sensory impairment is typically not present, and cognition and bulbar function are normal (summary by Sumner et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of distal HMN (dHMN), see HMN type I (HMN1; 182960). Clinical Features Boylan et al. (1995) reported a large multigenerational family of English and German descent in which 9 living individuals and 1 deceased individual were diagnosed with distal spinal muscular atrophy. Affected individuals developed distal leg weakness, often associated with exertional limb pain and cramps, between the second and fourth decades. Features included calf muscle atrophy, ankle weakness with inability to toe-walk or stand on toes, and loss of ankle reflexes. Seven patients also developed proximal lower limb weakness. Four patients had pes cavus and 1 had pes planus. All remained ambulatory, but older patients required a cane or foot orthoses. Most patients had upper extremity weakness, particularly of the triceps and intrinsic hand muscles. There were no cognitive, bulbar, bowel, or bladder symptoms. Sensory symptoms were mostly absent, except in the oldest patient who was found to have vitamin B12 deficiency. EMG studies were consistent with a neurogenic process; fibrillations and fasciculations were also observed in some patients. Muscle biopsies showed neurogenic atrophy and a reduction in the number of intramuscular nerve axons. Sumner et al. (2013) reported follow-up of the family described by Boylan et al. (1995) and also reported a father and son from an unrelated family with the same disorder. Overall, the age at onset ranged between 17 and 48 years, although 1 patient had onset at age 13 years. Some patients had difficulty running and walking, and 3 patients had lost independent ambulation at ages 82, 45, and 48 years, respectively, but the severity was variable. Inheritance The transmission pattern of distal spinal muscular atrophy in the family reported by Boylan et al. (1995) was consistent with autosomal dominant inheritance. Molecular Genetics In 2 unrelated families with autosomal dominant distal hereditary motor neuronopathy type IID, Sumner et al. (2013) identified a heterozygous missense mutation in the FBXO38 gene (C206R; 608533.0001). The mutation was found in the first family (Boylan et al., 1995) by exome sequencing. Sanger and whole-exome sequencing of 192 additional subjects with dHMN identified the same heterozygous C206R mutation in the second family. In vitro studies showed that the mutant protein was unable to promote activation of KLF7 (604865) target genes, including CDKN1A (116899) and L1CAM (308840). Primary motor neurons transfected with the mutant FBXO38 gene showed suppression of primary neurite outgrowth compared to wildtype, although the number of neurites was similar to wildtype. The findings suggested that this transcriptional pathway has a role in axonal development and neuronal maintenance. Sumner et al. (2013) stated that further studies would be needed to determine whether the mutation caused haploinsufficiency, a dominant-negative effect, or a toxic gain of function. INHERITANCE \- Autosomal dominant SKELETAL Hands \- Weakness of the intrinsic hand muscles Feet \- Pes cavus (in some patients) MUSCLE, SOFT TISSUES \- Limb muscle weakness and atrophy, distal, neurogenic \- Proximal muscle weakness and atrophy (may occur later) \- Triceps weakness \- Exertional leg pain \- Muscle cramps \- Fasciculation \- Neurogenic atrophy seen on muscle biopsy \- Angular atrophic fibers NEUROLOGIC Central Nervous System \- Lower limbs weakness and atrophy, distal \- Lower limb weakness, proximal \- Upper limb weakness \- Loss of ankle reflexes \- Difficulty walking \- Difficulty running \- Inability to stand on toes \- Denervation seen on EMG MISCELLANEOUS \- Onset in second to fourth decade \- Slowly progressive \- Characterized by calf weakness at onset \- Variable severity \- Most patients remain ambulatory MOLECULAR BASIS \- Caused by mutation in the F-box only protein 38 gene (FBXO38, 608533.0001 ) ▲ 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	NEURONOPATHY, DISTAL HEREDITARY MOTOR, TYPE IID	c1854023	29,851	omim	https://www.omim.org/entry/615575	2019-09-22T15:51:35	{"doid": ["0111210"], "mesh": ["C535715"], "omim": ["615575"], "orphanet": ["139525"], "synonyms": ["Alternative titles", "HMN IID", "NEUROPATHY, DISTAL HEREDITARY MOTOR, TYPE IID", "SPINAL MUSCULAR ATROPHY, DISTAL, AUTOSOMAL DOMINANT, CALF-PREDOMINANT"]}
A number sign (#) is used with this entry because of evidence that autosomal recessive deafness-44 (DFNB44) is caused by homozygous mutation in the ADCY1 gene (103072) on chromosome 7p12. One such family has been reported. Clinical Features Ansar et al. (2004) reported a consanguineous Pakistani family (family 4009) with autosomal recessive nonsyndromic hearing loss. Affected individuals were said to have prelingual profound hearing loss affecting all frequencies. In a report of the same family, Santos-Cortez et al. (2014) found that of 6 affected members who underwent standard audiometric testing, 5 had bilateral symmetric mild to moderate hearing impairment, while 1 had asymmetric impairment with profound loss in the worse ear. Mapping Ansar et al. (2004) performed genomewide analysis in a consanguineous Pakistani family with autosomal recessive nonsyndromic hearing loss and showed linkage to a 20.9-cM interval on chromosome 7p14.1-q11.22 (maximum multipoint lod score of 5.0 at marker D7S1818). Molecular Genetics In affected members of the Pakistani family with nonsyndromic hearing loss reported by Ansar et al. (2004), Santos-Cortez et al. (2014) identified a homozygous truncating mutation in the ADCY1 gene (R1038X; 103072.0001). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with hearing loss in the family. INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Deafness, prelingual, profound (affects all frequencies) MISCELLANEOUS \- One consanguineous Pakistani reported (last curated July 2015) MOLECULAR BASIS \- Caused by mutation in the adenylate cyclase-1, brain gene (ADCY1, 103072.0001 ) ▲ 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	DEAFNESS, AUTOSOMAL RECESSIVE 44	c1857809	29,852	omim	https://www.omim.org/entry/610154	2019-09-22T16:05:01	{"doid": ["0110501"], "mesh": ["C565716"], "omim": ["610154"], "orphanet": ["90636"], "synonyms": ["Autosomal recessive isolated neurosensory deafness type DFNB", "Autosomal recessive isolated sensorineural deafness type DFNB", "Autosomal recessive non-syndromic neurosensory deafness type DFNB"]}
An infectious embryofetopathy that may present in an infant as a result of maternal infection early in pregnancy and subsequent fetal infection with rubella virus. The disorder can lead to deafness, cataract, and variety of other permanent manifestations including cardiac and neurological defects. ## Epidemiology Congenital rubella syndrome (CRS) has been reported to affect an estimated 100,000 infants each year, mainly in developing countries. ## Clinical description Acquired during the first 8-12 weeks of gestation, rubella infection may cause multiple fetal defects (up to 90% of cases) including neurological (microcephaly), ophthalmic (cataracts, microphthalmia, glaucoma, pigmentary retinopathy, chorioretinitis), auditory (sensorineural deafness), cardiac (peripheral pulmonary artery stenosis, patent ductus arteriosus or ventricular septal defects, etc) defects and fetal wastage or stillbirth. Infection occurring later in gestation is associated with a decline in the risk of birth defects. Fetal defects are rarely associated with maternal rubella occurring after the 14th week of pregnancy, although sensorineural hearing deficit can occur with infection as late as week 20. Additional findings may include: meningoencephalitis, interstitial pneumonitis hepatitis with jaundice (within 24 hours after birth), hepatosplenomegaly, purpura, squint, congenital glaucoma and developmental delay. Infants with congenitally acquired infection may develop manifestations of late-onset disease in later childhood or as adults. Endocrine organs, eyes, hearing and central nervous system may be affected and autoimmune disorders and/or behavioral problems may occur. ## Etiology In pregnant women the virus infects the placenta and the developing fetus. Infants with CRS may excrete the virus for a year or more in pharyngeal secretions and urine. ## Diagnostic methods In the prenatal period, ultrasound examination may fail to diagnose CRS but molecular analysis performed on amniotic fluid (collected at least 6 weeks after maternal infection and after 21 weeks of gestation) will confirm or infirm congenital infection. World Health Organization has established diagnostic criteria. In the postnatal period, its classic triad of clinical signs may suspect CRS: cataract, heart disease, and deafness and confirmed by positive Rubella specific IgM in the newborn. ## Differential diagnosis Differential diagnosis of maternal rubella includes all infections responsible of maculo-papular rash (parvovirus B19, measles, streptococcus A, enteroviruses, cytomegalovirus (CMV), Epstein-Barr virus, human immunodeficiency virus) and other rashes from non infectious causes. Differential diagnosis of congenital rubella includes congenital infection with Toxoplasma gondii, enteroviruses, CMV, Herpes simplex virus, Varicella, Syphilis. ## Management and treatment To date, no treatment for rubella or CRS is available. In order to prevent CRS, vaccination of adolescent girls and women of childbearing age is recommended. ## Prognosis Prognosis of rubella congenital infection mainly depends on the term at maternal infection. Infected children surviving the neonatal period may face serious developmental disabilities (for example, visual and hearing impairments) and have an increased risk for developmental delay, including autism, type I diabetes mellitus and thyroiditis. A progressive encephalopathy resembling subacute sclerosing leukoencephalitis has been observed in patients with CRS. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and 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 rubella syndrome	c0035921	29,853	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=290	2021-01-23T18:26:10	{"gard": ["4744"], "mesh": ["D012410"], "umls": ["C0035921"], "icd-10": ["P35.0"], "synonyms": ["CRS", "Fetal rubella syndrome", "Mother-to-child transmission of rubella syndrome"]}
Pathogen resistance to medications This article is about pathogen resistance to the effects of drugs. For human resistance to the effects of drugs, see Drug tolerance. An illustrative diagram explaining drug resistance. Drug resistance is the reduction in effectiveness of a medication such as an antimicrobial or an antineoplastic in treating a disease or condition.[1] The term is used in the context of resistance that pathogens or cancers have "acquired", that is, resistance has evolved. Antimicrobial resistance and antineoplastic resistance challenge clinical care and drive research. When an organism is resistant to more than one drug, it is said to be multidrug-resistant. The development of antibiotic resistance in particular stems from the drugs targeting only specific bacterial molecules (almost always proteins). Because the drug is so specific, any mutation in these molecules will interfere with or negate its destructive effect, resulting in antibiotic resistance.[2] Furthermore, there is mounting concern over the abuse of antibiotics in the farming of livestock, which in the European Union alone accounts for three times the volume dispensed to humans – leading to development of super-resistant bacteria.[3][4] Bacteria are capable of not only altering the enzyme targeted by antibiotics, but also by the use of enzymes to modify the antibiotic itself and thus neutralize it. Examples of target-altering pathogens are Staphylococcus aureus, vancomycin-resistant enterococci and macrolide-resistant Streptococcus, while examples of antibiotic-modifying microbes are Pseudomonas aeruginosa and aminoglycoside-resistant Acinetobacter baumannii.[5] In short, the lack of concerted effort by governments and the pharmaceutical industry, together with the innate capacity of microbes to develop resistance at a rate that outpaces development of new drugs, suggests that existing strategies for developing viable, long-term anti-microbial therapies are ultimately doomed to failure. Without alternative strategies, the acquisition of drug resistance by pathogenic microorganisms looms as possibly one of the most significant public health threats facing humanity in the 21st century.[6] ## Contents * 1 Types * 2 Mechanisms * 2.1 Mechanisms of Acquired Drug Resistance:[28] * 3 Metabolic cost * 4 Treatment * 5 See also * 6 References * 7 External links ## Types[edit] Drug, toxin, or chemical resistance is a consequence of evolution and is a response to pressures imposed on any living organism. Individual organisms vary in their sensitivity to the drug used and some with greater fitness may be capable of surviving drug treatment. Drug-resistant traits are accordingly inherited by subsequent offspring, resulting in a population that is more drug-resistant. Unless the drug used makes sexual reproduction or cell-division or horizontal gene transfer impossible in the entire target population, resistance to the drug will inevitably follow. This can be seen in cancerous tumors where some cells may develop resistance to the drugs used in chemotherapy.[7] Chemotherapy causes fibroblasts near tumors to produce large amounts of the protein WNT16B. This protein stimulates the growth of cancer cells which are drug-resistant.[8] MicroRNAs have also been shown to affect acquired drug resistance in cancer cells and this can be used for therapeutic purposes.[9] Malaria in 2012 has become a resurgent threat in South East Asia and sub-Saharan Africa, and drug-resistant strains of Plasmodium falciparum are posing massive problems for health authorities.[10][11] Leprosy has shown an increasing resistance to dapsone. A rapid process of sharing resistance exists among single-celled organisms, and is termed horizontal gene transfer in which there is a direct exchange of genes, particularly in the biofilm state.[12] A similar asexual method is used by fungi and is called "parasexuality". Examples of drug-resistant strains are to be found in microorganisms[13] such as bacteria and viruses, parasites both endo- and ecto-, plants, fungi, arthropods,[14][15] mammals,[16] birds,[17] reptiles,[18] fish, and amphibians.[18] In the domestic environment, drug-resistant strains of organism may arise from seemingly safe activities such as the use of bleach,[19] tooth-brushing and mouthwashing,[20] the use of antibiotics, disinfectants and detergents, shampoos, and soaps, particularly antibacterial soaps,[21][22] hand-washing,[23] surface sprays, application of deodorants, sunblocks and any cosmetic or health-care product, insecticides, and dips.[24] The chemicals contained in these preparations, besides harming beneficial organisms, may intentionally or inadvertently target organisms that have the potential to develop resistance.[25] ## Mechanisms[edit] The four main mechanisms by which microorganisms exhibit resistance to antimicrobials are:[26][27] 1. Drug inactivation or modification: e.g., enzymatic deactivation of Penicillin G in some penicillin-resistant bacteria through the production of β-lactamases. 2. Alteration of target site: e.g., alteration of PBP — the binding target site of penicillins — in MRSA and other penicillin-resistant bacteria. 3. Alteration of metabolic pathway: e.g., some sulfonamide-resistant bacteria do not require para-aminobenzoic acid (PABA), an important precursor for the synthesis of folic acid and nucleic acids in bacteria inhibited by sulfonamides. Instead, like mammalian cells, they turn to utilizing preformed folic acid. 4. Reduced drug accumulation: by decreasing drug permeability and/or increasing active efflux (pumping out) of the drugs across the cell surface. ### Mechanisms of Acquired Drug Resistance:[28][edit] [29] Mechanism Antimicrobial Agent Drug Action Mechanism of Resistance Destroy drug Aminoglycoside Beta-lactam antibiotics (penicillin and cephalosporin) Chloramphenicol Binds to 30S Ribosome subunit, inhibiting protein synthesis Binds to penicillin-binding proteins, Inhibiting peptidoglycan synthesis Bind to 50S ribosome subunit, inhibiting formation of peptide bonds Plasmid encode enzymes that chemically alter the drug (e.g., by acetylation or phosphorylation), thereby inactivating it. Plasmid encode beta-lactamase, which open the beta-lactam ring, inactivating it. Plasmid encode an enzyme that acetylate the drug, thereby inactivating it. Alters drug target Aminoglycosides Beta-lactam antibiotics (penicillin and cephalosporin) Erythromycin Quinolones Rifampin Trimethoprim Binds to 30S Ribosome subunit, inhibiting protein synthesis Binds to penicillin-binding proteins, Inhibiting peptidoglycan synthesis Bind to 50S ribosome subunit, inhibiting protein synthesis Binds to DNA topoisomerase, an enzyme essential for DNA synthesis Binds to the RNA polymerase; inhibiting initiation of RNA synthesis Inhibit the enzyme dihydrofolate reduces, blocking the folic acid pathway Bacteria make an altered 30S ribosomes that does not bind to the drug. Bacteria make an altered penicillin-binding proteins, that do not bind to the drug. Bacteria make a form of 50S ribosome that does not binds to the drug. Bacteria make an altered DNA topoisomerase that does not binds to the drug. Bacteria make an altered polymerase that does not binds to the drug. Bacteria make an altered enzyme that does not binds to the drug. Inhibits drug entry or removes drug Penicillin Erythromycin Tetracycline Binds to penicillin-binding proteins, Inhibiting peptidoglycan synthesis Bind to 50S ribosome subunit, inhibiting protein synthesis Binds to 30S Ribosome subunit, inhibiting protein synthesis by blocking tRNA Bacteria change shape of the outer membrane porin proteins, preventing drug from entering cell. New membrane transport system prevent drug from entering cell. New membrane transport system pumps drug out of cell. ## Metabolic cost[edit] Biological cost is a measure of the increased energy metabolism required to achieve a function. Drug resistance has a high metabolic price[30] in pathogens for which this concept is relevant (bacteria,[31] endoparasites, and tumor cells.) In viruses, an equivalent "cost" is genomic complexity. The high metabolic cost means that, in the absence of antibiotics, a resistant pathogen will have decreased evolutionary fitness as compared to susceptible pathogens.[32] This is one of the reasons drug resistance adaptations are rarely seen in environments where antibiotics are absent. However, in the presence of antibiotics, the survival advantage conferred off-sets the high metabolic cost and allows resistant strains to proliferate. ## Treatment[edit] In humans, the gene ABCB1 encodes MDR1(p-glycoprotein) which is a key transporter of medications on the cellular level. If MDR1 is overexpressed, drug resistance increases.[33] Therefore, ABCB1 levels can be monitored.[33] In patients with high levels of ABCB1 expression, the use of secondary treatments, like metformin, have been used in conjunction with the primary drug treatment with some success.[33] For antibiotic resistance, which represents a widespread problem nowadays, drugs designed to block the mechanisms of bacterial antibiotic resistance are used. For example, bacterial resistance against beta-lactam antibiotics (such as penicillin and cephalosporins) can be circumvented by using antibiotics such as nafcillin that are not susceptible to destruction by certain beta-lactamases (the group of enzymes responsible for breaking down beta-lactams).[34] Beta-lactam bacterial resistance can also be dealt with by administering beta-lactam antibiotics with drugs that block beta-lactamases such as clavulanic acid so that the antibiotics can work without getting destroyed by the bacteria first.[35] Recently, researchers have recognized the need for new drugs that inhibit bacterial efflux pumps, which cause resistance to multiple antibiotics such as beta-lactams, quinolones, chloramphenicol, and trimethoprim by sending molecules of those antibiotics out of the bacterial cell.[36][37] Sometimes a combination of different classes of antibiotics may be used synergistically; that is, they work together to effectively fight bacteria that may be resistant to one of the antibiotics alone.[38] Destruction of the resistant bacteria can also be achieved by phage therapy, in which a specific bacteriophage (virus that kills bacteria) is used.[39] ## See also[edit] * Antibiotic resistance * Fecal bacteriotherapy * Mass drug administration * Multidrug resistance * Pharmacoepidemiology * Physical factors affecting microbial life * Small multidrug resistance protein * Eleftheria terrae ## References[edit] 1. ^ Alfarouk, KO; Stock, CM; Taylor, S; Walsh, M; Muddathir, AK; Verduzco, D; Bashir, AH; Mohammed, OY; Elhassan, GO; Harguindey, S; Reshkin, SJ; Ibrahim, ME; Rauch, C (2015). "Resistance to cancer chemotherapy: failure in drug response from ADME to P-gp". Cancer Cell International. 15: 71. doi:10.1186/s12935-015-0221-1. PMC 4502609. PMID 26180516. 2. ^ "Antibiotic Resistance and Evolution". detectingdesign.com.[verification needed] 3. ^ Harvey, Fiona (16 October 2016). "Use of strongest antibiotics rises to record levels on European farms". the Guardian. Retrieved 1 October 2018.[verification needed] 4. ^ Duckenfield, Joan (2011-12-30). "Antibiotic Resistance Due to Modern Agricultural Practices: An Ethical Perspective". Journal of Agricultural and Environmental Ethics. 26 (2): 333–350. doi:10.1007/s10806-011-9370-y. ISSN 1187-7863. S2CID 55736918.[verification needed] 5. ^ Fisher, Jed F.; Mobashery, Shahriar (2010). "Enzymology of Bacterial Resistance". Comprehensive Natural Products II. Volume 8: Enzymes and Enzyme Mechanisms. Elsevier. pp. 443–201. doi:10.1016/B978-008045382-8.00161-1. ISBN 978-0-08-045382-8.[verification needed] 6. ^ "Reading: The Resistance Phenomenon in Microbes and Infectious Disease Vectors: Implications for Human Health and Strategies for Containment -- Workshop Summary - The National Academies Press". nap.edu.[verification needed] 7. ^ "Tolerance and Resistance to Drugs". Merck Manuals Consumer Version. 8. ^ "Chemo 'Undermines Itself' Through Rogue Response",BBC News, 5 August 2012. 9. ^ Ghasabi M, Mansoori B, Mohammadi A, Duijf PH, Shomali N, Shirafkan N, Mokhtarzadeh A, Baradaran B (2019). "MicroRNAs in cancer drug resistance: Basic evidence and clinical applications". Journal of Cellular Physiology. x (3): 2152–2168. doi:10.1002/jcp.26810. PMID 30146724. S2CID 52092652. 10. ^ McGrath, Matt (2012-04-05). "Resistance spread 'compromising' fight against malaria". BBC News. 11. ^ Morelle R (20 October 2015). "Drug-resistant malaria can infect African mosquitoes". BBC News. Retrieved 21 October 2015. 12. ^ Molin S, Tolker-Nielsen T (June 2003). "Gene transfer occurs with enhanced efficiency in biofilms and induces enhanced stabilisation of the biofilm structure". Current Opinion in Biotechnology. 14 (3): 255–61. doi:10.1016/S0958-1669(03)00036-3. PMID 12849777. 13. ^ "Mechanisms of drug action and resistance". tulane.edu. 14. ^ Brun LO, Wilson JT, Daynes P (March 1983). "Ethion resistance in the cattle tick (Boophilus microplus) in New Caledonia" (PDF). International Journal of Pest Management. 29 (1): 16–22. doi:10.1080/09670878309370763. 15. ^ "Review Article on Colorado Potato Beetle Resistance to Insecticides". potatobeetle.org. Retrieved 1 October 2018. 16. ^ Lund M (1972). "Rodent resistance to the anticoagulant rodenticides, with particular reference to Denmark". Bulletin of the World Health Organization. 47 (5): 611–8. PMC 2480843. PMID 4540680. 17. ^ Shefte N, Bruggers RL, Schafer EW (April 1982). "Repellency and toxicity of three bird control chemicals to four species of African grain-eating birds". The Journal of Wildlife Management. 46 (2): 453–7. doi:10.2307/3808656. JSTOR 3808656. 18. ^ a b "Reptiles Magazine, your source for reptile and herp care, breeding, and enthusiast articles". reptilechannel.com. Archived from the original on 2011-01-03. 19. ^ "How household bleach works to kill bacteria". physorg.com. 20. ^ "Compete50 The complete mouth care products". Archived from the original on 2010-04-03. Retrieved 2010-07-18. 21. ^ "The Dirt on Clean: Antibacterial Soap v Regular Soap". CBC News. Archived from the original on 6 August 2011. 22. ^ "Should antibacterial soap be outlawed?". HowStuffWorks. 2007-11-07. 23. ^ Weber DJ, Rutala WA (October 2006). "Use of germicides in the home and the healthcare setting: is there a relationship between germicide use and antibiotic resistance?". Infection Control and Hospital Epidemiology. 27 (10): 1107–19. doi:10.1086/507964. PMID 17006819. S2CID 20734025. 24. ^ Yoon KS, Kwon DH, Strycharz JP, Hollingsworth CS, Lee SH, Clark JM (November 2008). "Biochemical and molecular analysis of deltamethrin resistance in the common bed bug (Hemiptera: Cimicidae)". Journal of Medical Entomology. 45 (6): 1092–101. doi:10.1603/0022-2585(2008)45[1092:BAMAOD]2.0.CO;2. PMID 19058634. 25. ^ "Antibacterial cleaning products". Australian Department of Health & Human Services. Archived from the original on 4 March 2015. Retrieved 1 October 2018. 26. ^ Li XZ, Nikaido H (August 2009). "Efflux-mediated drug resistance in bacteria: an update". Drugs. 69 (12): 1555–623. doi:10.2165/11317030-000000000-00000. PMC 2847397. PMID 19678712. 27. ^ Sandhu P, Akhter Y (January 2018). "Evolution of structural fitness and multifunctional aspects of mycobacterial RND family transporters". Archives of Microbiology. 200 (1): 19–31. doi:10.1007/s00203-017-1434-6. PMID 28951954. S2CID 13656026. 28. ^ Catherine A. Ingraham, John L. Ingraham (2000). Introduction to Microbiology second edition. 29. ^ Catherine A. Ingraham, John L. Ingraham (2000). Introduction to Microbiology. 30. ^ Gillespie SH, McHugh TD (September 1997). "The biological cost of antimicrobial resistance". Trends in Microbiology. 5 (9): 337–9. doi:10.1016/S0966-842X(97)01101-3. PMID 9294886. 31. ^ Wichelhaus TA, Böddinghaus B, Besier S, Schäfer V, Brade V, Ludwig A (November 2002). "Biological cost of rifampin resistance from the perspective of Staphylococcus aureus". Antimicrobial Agents and Chemotherapy. 46 (11): 3381–5. doi:10.1128/AAC.46.11.3381-3385.2002. PMC 128759. PMID 12384339. 32. ^ Händel, Nadine; Schuurmans, J. Merijn; Brul, Stanley; ter Kuile, Benno H. (August 2013). "Compensation of the Metabolic Costs of Antibiotic Resistance by Physiological Adaptation in Escherichia coli". Antimicrobial Agents and Chemotherapy. 57 (8): 3752–3762. doi:10.1128/AAC.02096-12. ISSN 0066-4804. PMC 3719774. PMID 23716056. 33. ^ a b c Ramos-Peñafiel C, Olarte-Carrillo I, Cerón-Maldonado R, Rozen-Fuller E, Kassack-Ipiña JJ, Meléndez-Mier G, Collazo-Jaloma J, Martínez-Tovar A (September 2018). "Effect of metformin on the survival of patients with ALL who express high levels of the ABCB1 drug resistance gene". Journal of Translational Medicine. 16 (1): 245. doi:10.1186/s12967-018-1620-6. PMC 6122769. PMID 30176891. 34. ^ Barber M, Waterworth PM (August 1964). "Penicillinase-resistant Penicillins and Cephalosporins". British Medical Journal. 2 (5405): 344–9. doi:10.1136/bmj.2.5405.344. PMC 1816326. PMID 14160224. 35. ^ Bush K (January 1988). "Beta-lactamase inhibitors from laboratory to clinic". Clinical Microbiology Reviews. 1 (1): 109–23. doi:10.1128/CMR.1.1.109. PMC 358033. PMID 3060240. 36. ^ Webber MA, Piddock LJ (January 2003). "The importance of efflux pumps in bacterial antibiotic resistance". The Journal of Antimicrobial Chemotherapy. 51 (1): 9–11. doi:10.1093/jac/dkg050. PMID 12493781. 37. ^ Tegos GP, Haynes M, Strouse JJ, Khan MM, Bologa CG, Oprea TI, Sklar LA (2011). "Microbial efflux pump inhibition: tactics and strategies". Current Pharmaceutical Design. 17 (13): 1291–302. doi:10.2174/138161211795703726. PMC 3717411. PMID 21470111. 38. ^ Glew RH, Millering RS, Wennersten C (June 1975). "Comparative synergistic activity of nafcillin, oxacillin, and methicillin in combination with gentamicin against". Antimicrobial Agents and Chemotherapy. 7 (6): 828–32. doi:10.1128/aac.7.6.828. PMC 429234. PMID 1155924. 39. ^ Lin, Derek M; Koskella, Britt; Lin, Henry C (2017). "Phage therapy: An alternative to antibiotics in the age of multi-drug resistance". World Journal of Gastrointestinal Pharmacology and Therapeutics. 8 (3): 162–173. doi:10.4292/wjgpt.v8.i3.162. ISSN 2150-5349. PMC 5547374. PMID 28828194. ## External links[edit] * BURDEN of Resistance and Disease in European Nations—An EU project to estimate the financial burden of antibiotic resistance in European hospitals * Merck - Tolerance and Resistance * Cosmetics Database * HCMV drug resistance mutations tool * Combating Drug Resistance \- An informative article on multidrug resistance * Battle of the Bugs: Fighting Antibiotic Resistance * MDRIpred : A web server for predicting inhibitors against drug tolerant M. Tuberculosis, published in Chemistry Central Journal * CancerDR: Cancer Drug Resistance Database. Scientific Reports 3, 1445 * v * t * e Pharmacology Ligand (biochemistry) Excitatory * Agonist * Endogenous agonist * Irreversible agonist * Partial agonist * Superagonist * Physiological agonist Inhibitory * Antagonist * Competitive antagonist * Irreversible antagonist * Physiological antagonist * Inverse agonist * Enzyme inhibitor * Drug * Neurotransmitter * Agonist-antagonist * Pharmacophore Pharmacodynamics Activity at receptor * Mechanism of action * Mode of action * Binding * Receptor (biochemistry) * Desensitization (pharmacology) Other effects of ligand * Selectivity (Binding, Functional) * Pleiotropy (drugs) * Non-specific effect of vaccines * Adverse effects * Toxicity (Neurotoxicity) Analysis * Dose–response relationship * Hill equation (biochemistry) * Schild plot * Del Castillo Katz model * Cheng-Prussoff Equation * Methods (Organ bath, Ligand binding assay, Patch-clamp) Metrics * Efficacy * Intrinsic activity * Potency (EC50, IC50, ED50, LD50, TD50) * Therapeutic index * Affinity Pharmacokinetics Metrics * Loading dose * Volume of distribution (Initial) * Rate of infusion * Onset of action * Biological half-life * Plasma protein binding * Bioavailability LADME * (L)ADME: (Liberation) * Absorption * Distribution * Metabolism * Excretion (Clearance) * Compartment * Bioequivalence Related fields Neuroscience and psychology * Neuropsychopharmacology * Neuropharmacology * Psychopharmacology * Electrophysiology Medicine * Clinical pharmacology * Pharmacy * Medicinal chemistry * Pharmacoepidemiology Biochemistry and genetics * Pharmacoinformatics * Pharmacogenetics * Pharmacogenomics Toxicology * Pharmacotoxicology * Neurotoxicology Drug discovery * Classical pharmacology * Reverse pharmacology * Photopharmacology * Immunopharmacology * Cell biology * Physiology Other * Coinduction (anaesthetics) * Combination therapy * Functional analog (chemistry) * Polypharmacology * Chemotherapy * List of drugs * WHO list of essential medicines Tolerance and resistance * Drug tolerance * Tachyphylaxis * Drug resistance * Antibiotic resistance * Multiple drug resistance Antimicrobial pharmacology * Antimicrobial pharmacodynamics * Minimum inhibitory concentration * Bacteriostatic * Minimum bactericidal concentration * Bactericide Authority control * GND: 4136408-9 * LCCN: sh85039708 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Drug resistance	None	29,854	wikipedia	https://en.wikipedia.org/wiki/Drug_resistance	2021-01-18T18:58:21	{"mesh": ["D004351"], "umls": ["C0013203"], "wikidata": ["Q12147416"]}
Brachydactyly type B (BDB) is a condition characterized by incomplete development (hypoplasia) or absence of the outermost bones of the fingers and toes (distal phalanges) and nails. Additional features may include hypoplasia of the middle phalanges, fusion of the joints (symphalangism), broad thumbs, and webbed fingers (syndactyly). The feet are often less severely affected than the hands. There are 2 types of this condition, designated as type 1 and 2. BDB type 1 is caused by mutations in the ROR2 gene. BDB type 2 is caused by mutations in the NOG gene. Inheritance of both types is autosomal dominant. Treatment may include surgery if the condition affects hand function, or for cosmetic reasons. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and 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 type B	c1862112	29,855	gard	https://rarediseases.info.nih.gov/diseases/985/brachydactyly-type-b	2021-01-18T18:01:44	{"mesh": ["C566196"], "omim": ["113000", "611377"], "umls": ["C1862112"], "orphanet": ["93383"], "synonyms": []}
Indolent T cell lymphoproliferative disorder of the gastrointestinal tract Other namesIndolent lymphoma SpecialtyHematology and Oncology SymptomsCommon GI tract symptoms CausesGrowth of benign T cells Risk factorsMay progress to a lymphoma Differential diagnosisMimics certain lymphomas TreatmentNone except routine follow-ups to detect malignant progression PrognosisGuarded Indolent T cell lymphoproliferative disorder of the gastrointestinal tract or Indolent T cell lymphoproliferative disorder of the GI tract (ITCLD-GT) is a rare and recently recognized disorder in which mature T cell lymphocytes accumulation abnormally in the gastrointestinal tract (GI tract).[1] This accumulation causes various lesions (e.g. polyps, thickened mucosal folds, small areas of redness, and superficial ulcerations) in the mucosal layer lining the GI tract. Individuals with ITCLD-GT commonly complain of chronic GI tract symptoms such as nausea, vomiting, diarrhea, abdominal pain, and rectal bleeding.[2] Carbonnell et al.[3] first described a case of an indolent GI tract lymphoproliferation disorder in 1994 and defined the lymphocytes involved in it to be T cells expressing the CD4 glycoprotein on their surface membranes. Subsequent studies reported on patients who had a similar indolent GI tract disorder that involved T cells which expressed either the CD4, CD8, or neither surface membrane glycoprotein. The disorder resembled certain aggressive GI tract lymphomas and was variably termed indolent lymphoma or indolent T cell lymphoproliferative disorder of the gastrointestinal tract.[4] However, the disease differed from the aggressive lymphomas which it mimicked in having a prolonged and usually non-progressive course. Furthermore, the disorder's lesions consisted of normal-appearing T cells that proliferated very slowly and usually caused little or no tissue destruction.[5] In 2017, the World Health Organization provisionally classified ITCLD-GT as an extranodal (i.e. usually not involving lymph nodes), indolent disorder in which various subtypes of T cells proliferate in the GI tract.[6] While usually acting like a benign disease, ITCLD-GT has malignant features: 1) its normal-appearing T cells are clonal in nature, i.e. descended from a single cell;[6] 2) these T cells may contain genetic abnormalities[7] that are known to occur in and contribute to the development of very aggressive lymphomas;[8] and 3) ITCLD-GI, after many years of indolent behavior, may progress to an aggressive lymphoma.[2] Thus, ITCLD-GT can act as a premalignat disorder. Nonetheless, most cases of it run an indolent, non-malignant course and when mistakenly treated as an aggressive lymphoma, do not responded to standard chemotherapy treatments.[5] The disorder has also been mistaken for, and found unresponsive to therapies that treat inflammatory or autoimmune bowel diseases.[1][4] Clinically, ITCLD-GT must be distinguished from the malignant, inflammatory, and autoimmune bowel diseases that it mimics in order to avoid useless and potentially harmful therapies.[5] ## Contents * 1 Presentation * 2 Pathophysiology * 2.1 T cells In ITCLD-GT * 3 Histology * 4 Diagnosis * 4.1 Laboratory studies * 4.2 Differential diagnosis * 5 Treatment * 6 Prognosis * 7 Course of the disorder * 8 References ## Presentation[edit] ITCLD-GT occurs more commonly in males of middle age (median age 48.4, range 15–77 years in one study).[2] Individuals with the disease present with GI tract symptoms which often are serious and/or debilitating[9] and may mimic those occurring in malignant lymphoproliferative, inflammatory, or autoimmune bowel diseases.[4] These symptoms include chronic epigastric pain, abdominal pain, heartburn, nausea, diarrhea, vomiting, weight loss, relapsing oral ulcers, relapsing colorectal ulcers, rectal bleeding, and/or night sweats.[4] Several patients presenting with these symptoms have been diagnosed with and unsuccessfully treated for peripheral T-cell lymphoma,[5] an inflammatory bowel disease (either Crohn disease or ulcerative colitis),[1] or the autoimmune GI tract disorder, celiac disease.[10] It has been shown or appears very likely that these patients had ITCLD-GT rather than the cited diagnoses.[1][5][10] ## Pathophysiology[edit] The lesions in ITCLD-GT consists of slowly growing, mature, and benign-appearing T cells. The reasons for their accumulations in the GI tract are unclear. However, these cells often carry potentially oncogenic mutations. In a recent study, the T cells in 4 of 5 patients with CD4+ T-cell disease carried a STAT3-JAK2 fusion gene.[6] This gene consists of a fusion between the STAT3 gene at position 2.2 on the long (or "g") arm of chromosome 17 (location abbreviated 17q21.2) and the JAK2 gene at position 24.1 on the short ("q") of chromosome 9 (9p24.1). The disorder in two of the patients with this t(9;17)(p24.1;q21/2) fusion gene progressed to malignant lymphomas.[9] Abnormalities in the expression and/or activity of STAT3 and JAK2[11] as well as various JAK2 fusion genes[9] are associated with the development and progression of various myeloproliferative and lymphoproliferative malignancies. These findings suggest that the STAT3-JAK2-fusion gene may contribute to the malignant progression and perhaps development of CD4+ ITCLD-GT.[9] Numerous other genetic abnormalities occur in the T-cells of ITCLD-GT but unlike the STAT3-JAK fusion gene have been limited to single cases. These abnormalities include trisomy of chromosome 5, a t(4;16)(q26;p13) fusion between interleukin-2 and B-cell maturation antigen genes, loses in the 4p26 and 16p13 chromosomal areas involved in formation of the t(4;16)9q26;p13) fusion gene, and one or more copy-number variations in diverse areas of different chromosomes.[4] The role(s), if any, of these abnormalities in ITCLD-GT is unclear.{{citation needed} ### T cells In ITCLD-GT[edit] The cells involved in all cases of ITCLD-GT are mature T cells[1] that exhibit a clonal rearrangement of their T cell receptors and, therefore, are derived from a common ancestry cell.[4] They express the αβ as opposed to the γδ surface membrane T-cell receptor and therefore are αβ rather than γδ T-cells. In all reported cases, these T cells express the CD3 cluster of differentiation protein complex but vary in their expression of the CD4 cluster of differentiation glycoprotein as well as the CD8 glycoprotein component of the T cell receptor. Individuals with ITCLD-GT, therefore, have pathological accumulations of either CD4+, CD8+, or, very rarely, CD4-, CD8- T cells.[4] A single case of CD4+, CD8+ T cell disease has been reported recently.[9] There may be differences in the presentation, course, and malignant potential of ITCLD-GT based or these different expressions of CD4 and CD8 but this requires further study. Unlike certain types of T cell lymphomas for which it has been mistaken, the T cells in ITCLD-GT do not express the neutral cell adhesion molecule, CD56, and are not infected with the Epstein-Barr virus and therefore do not express this virus's latency proteins or latency ncRNAs.[1] The origin of these cells is unknown but it is thought that the CD4+ and CD8+ T-cells derive from mucosal T helper and cytotoxic T lymphocytes, respectively. The CD4-, CD8- T cells that may cause rare cases of the disorder exhibit cytology and morphology features of both of the latter two mucosal cell types.[4] ## Histology[edit] Histological analysis of tissues biopsied from the GI tract generally reveals dense infiltrates of small, mature lymphocytes in the mucosa that may displace[2] but usually do not invade[4] the epithelium; these cells sometimes extend through the muscularis mucosa to invade the submucosa.[4] The lesions may contain reactive plasma cells, eosinophils, granulomas (in CD4+ disease), and lymphoid follicles.[2] There is little or no tissue destruction.[1] Immunohistochemistry analyses indicate that the small lymphocytes are CD4+,[9] CD8+,[9] CD4-/CD8-,[4] or CD4+/CD8+ T-cells[9] that stain for CD3[4] but not CD56 or Epstein-Barr virus products.[1] Notably, the afflicted T cells have an extremely low rate of proliferation as determined by examining their KI-67 protein using immunofluorescence analysis.[4] ## Diagnosis[edit] The diagnosis of indolent T cell lymphoproliferative disorder of the GI tract depends on identifying the presentation, clinical course, and laboratory and histological findings given in the previous four sections.[4] (Future studies may find that the diagnosis is supported by demonstrating the presence of the STAT3-JAK2 fusion gene in the CD4+ T cells of suspicious tissues.[6]) ### Laboratory studies[edit] Inspection of the entire GI tract by endoscopy and colonscopy generally finds mucosal redness, erosions, small superficial ulcerations, occasional small polyps,[2] fissures, diverticula, and, rarely, tumor-like masses and deep ulcers.[4] These lesions may be localized, occur in multiple sites, or extend throughout the GI tract;[4] they are more common in the small intestine and colon[2] but can also occur in the stomach, esophagus, oral cavity (e.g. palate), and rectum.[4] Whole body computed tomography scans (i.e. CT scans) frequently find enlarged mesenteric lymph nodes (i.e. lymph nodes attached to the intestinal mesentery) and may show evidence of liver, spleen, and/or other organ involvement in cases which are advancing or have advanced to a malignant lymphoma. Positron emission tomography scans (i.e. PET scans) and positron emission tomography–computed tomography scans (i.e. PET-CT scans) likewise often show that the mesenteric lymph nodes in ITCLD-GT exhibit modestly increased metabolic or biochemical activity and, in cases of progressing or overt malignant disease, show increased activity in other organs.[4] Inspection of patients' peripheral blood smearss and bone marrow tissues may identify excessive numbers of ITCLD-GT's T cells and thereby likewise indicate progressing or malignant disease.[2] ### Differential diagnosis[edit] Because of the radical differences in their prognoses and treatments, ITCLD-GT should be distinguished from the malignant, inflammatory, autoimmune, and other diseases that it can mimic. Key findings that distinguish ITCLD-GT from the following major diseases which ITCLD-GT may mimic are: * Extranodal NK/T-cell lymphoma, nasal type (ENKTCL-NT]: Unlike ITCLD-GT, ENKTCL-NT a) is an Epstein-Barr virus-associated lymphoproliferative disease that commonly involves midline areas of the nasal cavity, oral cavity, and pharynx but may involve the GI tract; b) is a malignant and aggressive disease when involving the GI tract in areas below pharynx; c) usually involves rapidly proliferating malignant NK rather than T cells; d) commonly causes tissue-destructive lesions that are spread through multiple layers of the GI tract; and e) has lesions consisting of rapidly proliferating lymphocytes which express Epstein-Barr virus products, CD56, and one or more of various specific genetic abnormalities (see Genetic abnormalities in ENKTCL-NT).[12] * Monomorphic epithelieotropic intestinal lymphoma (MEITL) (formerly termed Type II enteropathy-associate T-cell lymphoma): Unlike ITCLD-GT, MEITL a) is a highly aggressive lymphoma of the GI tract that usually takes a short, lethal course; b) has lesions in which rapidly proliferating T cells accumulate in the mucosa and epithelium of the GI tract; and c) involves T cells that are CD4-, CD56-, and MAKT+, often express the γδ rather than the αβ T cell receptor,[13] and in rare cases are infected with, and express products made by, the Epstein-Barr virus.[14] * Peripheral T-cell lymphoma subtype peripheral T-cell lymphoma not otherwise specified (PTCL-NOS): Unlike ITCLD-GT, PTCL-NOS a) is a heterogenous disease that typically involves peripheral lymph nodes but only rarely develops in the GI tract[15] and b) is characterized by the rapid proliferation of CD4+ T cells that overexpress either GATA3 or TBX21, have a wide range of characteristic genetic abnormalities (see genetic abnormalities in PTCL, NOS), and in ~30% of cases are infected with, and express products made by, the Epstein-Barr virus.[16] * Celiac disease: A high proportion of patients with CD4+ ITCLD-GT and rare cases of CD8+ ITCLD-GT have been misdiagnosed as having celiac disease. Unlike celiac disease, ITCLD-GT: a) is unresponsive to gluten-free diets: b) is negative for antigens detected in standard celiac disease serology blood tests such as anti-transglutaminase antibodies; c) has infiltrating clonal T cells which do not express HLA-DQ2 or HLA-DQ8 human leukocyte antigens; and d) have lesions populated by mature, slowly proliferating clonal T cells which are CD56- and either CD4+, CD8+, CD4+/CD8+, or CD4-/CD8-. However, rare patients have been inflicted with both celiac disease and ITCLD-GT.[4] * Crohn's disease: Crohn's disease has been diagnosed in cases which were later diagnosed as ITCLD-GT perhaps because some patients with ITCLD-GT have histopathologic features (particularly the presence of granulomas)) that are characteristic of Crohn's disease. Awareness of ITCLD-GT and the histologic, clinical, and endoscopic differences between it and Crohn's disease should point to the proper diagnosis.[4] * Ulcerative colitis: Rare wcases of ITCLD-GT appear to have been diagnosed as ulcerative colitis. Awareness of ITCLD-GT and the histologic, clinical, and endoscopic differences between it and ulcerative colitis should point to the proper diagnosis.[4] * Natural killer cell enteropathy (NKCE): NKCE is an indolent disease in which lymphocytes proliferate in the GI tract to cause lesions and symptoms that resemble ITCLD-GT. NKCE differs from ITCLD-GT in that it: a) involves the proliferation of non-clonal NK cell rather than T cell lymphocytes; b) does now show evidence of mesenteric lymph node or other organ involvement; and c) does not progress to a malignant disease.[17] ## Treatment[edit] Studies indicate that patients with ITCLD-GT should be treated conservatively. Chemotherapy regimens directed at malignant lymphoma and treatment regimens used to treat celiac disease, Crohn's disease, or ulcerative colitis have had little or no beneficial effects on the course of the disease.[4] Patients should be follow regularly with peripheral blood and bone marrow examinations, GI tract endoscopic examinations[4] and PET scans[2] in order to detect the progression of ITCLD-GT to a malignant phase. ## Prognosis[edit] Studies to date indicate that most patients suffer a prolonged course of persistent or recovering-relapsing GI tract symptoms. A small percentage of patients have had spontaneous and sustained recoveries or progressed to a malignant lymphoma.[4] ## Course of the disorder[edit] Most patients with ITCLD-GT have chronic, relapsing and recurring GI tract symptoms that persist over many years. In one retrospective study, 19 of 23 patients with CD4+ ITCLD-GT had persistent disease over a follow-up period of 1–14 years (median 4.8 years), 2 of 23 patients had clinical and morphologic (i.e. negative GI tract evaluations) remissions enduring for at least 5–7 years, and 1 of 23 patients developed and died from a large-cell lymphoma of undetermined type. In the same study, 10 of 10 patients with CD8+ ITCLD-GT had persistent disease that had not progressed to a malignancy over an observation period of 1–18 years (median 2 years) although one patient had developed bone marrow involvement and therefore may have had disease which was in the process of transforming to a malignant state.[4] Other reports have found that the disorder in one patient with CD4-, CD8- ITCLD-GT disease progressed to involve the liver[5] and the disorder in two patients with CD4+ ITCLD-GT disease progressed to an undetermined type of large T-cell lymphoma.[9] In another retrospective analysis, 6 of 34 (17.6%) patients with ITCLD-GT progressed to a malignant state as evidenced by its spread to the blood or bone marrow: 2 (5.6%) patients died as a direct result of this spreading.[2] ## References[edit] 1. ^ a b c d e f g h Weindorf SC, Smith LB, Owens SR (November 2018). "Update on Gastrointestinal Lymphomas". Archives of Pathology & Laboratory Medicine. 142 (11): 1347–1351. doi:10.5858/arpa.2018-0275-RA. PMID 30407861. 2. ^ a b c d e f g h i j Foukas PG, de Leval L (January 2015). "Recent advances in intestinal lymphomas". Histopathology. 66 (1): 112–36. doi:10.1111/his.12596. PMID 25639480. 3. ^ Carbonnel F, Lavergne A, Messing B, Tsapis A, Berger R, Galian A, Nemeth J, Brouet JC, Rambaud JC (February 1994). "Extensive small intestinal T-cell lymphoma of low-grade malignancy associated with a new chromosomal translocation". Cancer. 73 (4): 1286–91. doi:10.1002/1097-0142(19940215)73:4<1286::AID-CNCR2820730425>3.0.CO;2-9. PMID 8313332. 4. ^ a b c d e f g h i j k l m n o p q r s t u v w x y Matnani R, Ganapathi KA, Lewis SK, Green PH, Alobeid B, Bhagat G (March 2017). "Indolent T- and NK-cell lymphoproliferative disorders of the gastrointestinal tract: a review and update". Hematological Oncology. 35 (1): 3–16. doi:10.1002/hon.2317. PMID 27353398. 5. ^ a b c d e f Ganapathi KA, Pittaluga S, Odejide OO, Freedman AS, Jaffe ES (September 2014). "Early lymphoid lesions: conceptual, diagnostic and clinical challenges". Haematologica. 99 (9): 1421–32. doi:10.3324/haematol.2014.107938. PMC 4562530. PMID 25176983. 6. ^ a b c d Lemonnier F, Gaulard P, de Leval L (September 2018). "New insights in the pathogenesis of T-cell lymphomas" (PDF). Current Opinion in Oncology. 30 (5): 277–284. doi:10.1097/CCO.0000000000000474. PMID 30028743. S2CID 51704108. 7. ^ Matutes E (May 2018). "The 2017 WHO update on mature T- and natural killer (NK) cell neoplasms". International Journal of Laboratory Hematology. 40 Suppl 1: 97–103. doi:10.1111/ijlh.12817. PMID 29741263. 8. ^ Taylor J, Xiao W, Abdel-Wahab O (July 2017). "Diagnosis and classification of hematologic malignancies on the basis of genetics". Blood. 130 (4): 410–423. doi:10.1182/blood-2017-02-734541. PMC 5533199. PMID 28600336. 9. ^ a b c d e f g h i Sharma A, Oishi N, Boddicker RL, Hu G, Benson HK, Ketterling RP, Greipp PT, Knutson DL, Kloft-Nelson SM, He R, Eckloff BW, Jen J, Nair AA, Davila JI, Dasari S, Lazaridis KN, Bennani NN, Wu TT, Nowakowski GS, Murray JA, Feldman AL (May 2018). "Recurrent STAT3-JAK2 fusions in indolent T-cell lymphoproliferative disorder of the gastrointestinal tract". Blood. 131 (20): 2262–2266. doi:10.1182/blood-2018-01-830968. PMC 5958657. PMID 29592893. 10. ^ a b Margolskee E, Jobanputra V, Lewis SK, Alobeid B, Green PH, Bhagat G (2013). "Indolent small intestinal CD4+ T-cell lymphoma is a distinct entity with unique biologic and clinical features". PLOS ONE. 8 (7): e68343. Bibcode:2013PLoSO...868343M. doi:10.1371/journal.pone.0068343. PMC 3701677. PMID 23861889. 11. ^ Cahu X, Constantinescu SN (December 2015). "Oncogenic Drivers in Myeloproliferative Neoplasms: From JAK2 to Calreticulin Mutations". Current Hematologic Malignancy Reports. 10 (4): 335–43. doi:10.1007/s11899-015-0278-x. PMID 26370832. S2CID 28079297. 12. ^ Tse E, Kwong YL (April 2017). "The diagnosis and management of NK/T-cell lymphomas". Journal of Hematology & Oncology. 10 (1): 85. doi:10.1186/s13045-017-0452-9. PMC 5391564. PMID 28410601. 13. ^ Ondrejka S, Jagadeesh D (December 2016). "Enteropathy-Associated T-Cell Lymphoma". Current Hematologic Malignancy Reports. 11 (6): 504–513. doi:10.1007/s11899-016-0357-7. PMID 27900603. S2CID 13329863. 14. ^ Khan N, Ozkaya N, Moskowitz A, Dogan A, Horwitz S (September 2018). "Peripheral T-cell lymphoma - are we making progress?". Best Practice & Research. Clinical Haematology. 31 (3): 306–314. doi:10.1016/j.beha.2018.07.010. PMID 30213401. 15. ^ Sandell RF, Boddicker RL, Feldman AL (April 2017). "Genetic Landscape and Classification of Peripheral T Cell Lymphomas". Current Oncology Reports. 19 (4): 28. doi:10.1007/s11912-017-0582-9. PMC 5517131. PMID 28303495. 16. ^ 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. 17. ^ Xia D, Morgan EA, Berger D, Pinkus GS, Ferry JA, Zukerberg LR (January 2019). "NK-Cell Enteropathy and Similar Indolent Lymphoproliferative Disorders: A Case Series With Literature Review". American Journal of Clinical Pathology. 151 (1): 75–85. doi:10.1093/ajcp/aqy108. PMID 30212873. S2CID 52272766. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Indolent T cell lymphoproliferative disorder of the gastrointestinal tract	None	29,856	wikipedia	https://en.wikipedia.org/wiki/Indolent_T_cell_lymphoproliferative_disorder_of_the_gastrointestinal_tract	2021-01-18T18:47:17	{"wikidata": ["Q65079999"]}
Coronary steal (with its symptoms termed coronary steal syndrome or cardiac steal syndrome) is a phenomenon where an alteration of circulation patterns leads to a reduction in the blood flow directed to the coronary circulation.[1] It is caused when there is narrowing of the coronary arteries and a coronary vasodilator[2] is used – "stealing" blood away from those parts of the heart. This happens as a result of the narrowed coronary arteries being always maximally dilated to compensate for the decreased upstream blood supply. Thus, dilating the resistance vessels in the coronary circulation causes blood to be shunted away from the coronary vessels supplying the ischemic zones, creating more ischemia. ## Contents * 1 Cause * 1.1 Other causes * 2 Diagnosis * 3 Treatment * 4 See also * 5 References ## Cause[edit] It is associated with dipyridamole. Hence, dipyridamole is a pharmacological success diagnostically, but a therapeutic failure because of the coronary steal phenomenon.[3] Coronary steal is also the mechanism in most drug-based cardiac stress tests; When a patient is incapable of doing physical activity they are given a vasodilator that produces a "cardiac steal syndrome" as a diagnostic procedure. The test result is positive if the patient's symptoms reappear or if ECG alterations are seen. It is also associated with the administration of Isoflurane, which is an inhaled anesthetic. Hydralazine can potentially cause this condition as well, as it is a direct arteriolar vasodilator. It has been associated with nitroprusside.[4] ### Other causes[edit] Coronary arteriovenous fistula between coronary artery and another cardiac chamber, like, the coronary sinus, right atrium, or right ventricle may cause steal syndrome under conditions like myocardial infarction and possible angina or ventricular arrhythmias, if the shunt is large in magnitude.[5] It can also be associated with new patterns of blood vessel growth.[6] ## Diagnosis[edit] This section is empty. You can help by adding to it. (October 2017) ## Treatment[edit] It is sometimes treated by surgery.[7] ## See also[edit] * Subclavian steal syndrome * Vascular resistance * Arteriolar vasodilator ## References[edit] 1. ^ Gould KL (August 1989). "Coronary steal. Is it clinically important?". Chest. 96 (2): 227–8. doi:10.1378/chest.96.2.227. PMID 2787728. 2. ^ Werner GS, Figulla HR; Figulla (July 2002). "Direct assessment of coronary steal and associated changes of collateral hemodynamics in chronic total coronary occlusions". Circulation. 106 (4): 435–40. doi:10.1161/01.CIR.0000022848.92729.33. PMID 12135942. 3. ^ Essentials of Medical Pharmacology, 5th Edition 4. ^ David L. Hoyt; Wilson, William J.; Grande, Christopher M. (2007). Trauma. Informa Healthcare. p. 304. ISBN 978-0-8247-2920-2. 5. ^ Harrisson's Principles of Internal Medicine, 17th Edition 6. ^ Aziz S, Stables RH; Stables (July 2005). "Coronary steal induced by angiogenesis following bypass surgery". Heart. 91 (7): 863. doi:10.1136/hrt.2004.043471. PMC 1768979. PMID 15958345. 7. ^ Kern MJ (1996). "Coronary steal through anomalous internal mammary artery graft treated by ligation without sternotomy". Tex Heart Inst J. 23 (4): 316–7. PMC 325384. PMID 8969040. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Coronary steal	c0340678	29,857	wikipedia	https://en.wikipedia.org/wiki/Coronary_steal	2021-01-18T18:30:29	{"umls": ["C0340678"], "wikidata": ["Q5172195"]}
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: "Splenomegaly" – news · newspapers · books · scholar · JSTOR (February 2010) (Learn how and when to remove this template message) Splenomegaly CT scan in a patient with chronic lymphocytic leukemia, showing splenomegaly. Yellow arrows point at the spleen. SpecialtyGeneral surgery Splenomegaly is an enlargement of the spleen.[1] The spleen usually lies in the left upper quadrant (LUQ) of the human abdomen. Splenomegaly is one of the four cardinal signs of hypersplenism which include: some reduction in number of circulating blood cells affecting granulocytes, erythrocytes or platelets in any combination; a compensatory proliferative response in the bone marrow; and the potential for correction of these abnormalities by splenectomy. Splenomegaly is usually associated with increased workload (such as in hemolytic anemias), which suggests that it is a response to hyperfunction. It is therefore not surprising that splenomegaly is associated with any disease process that involves abnormal red blood cells being destroyed in the spleen. Other common causes include congestion due to portal hypertension and infiltration by leukemias and lymphomas. Thus, the finding of an enlarged spleen, along with caput medusae, is an important sign of portal hypertension.[2] ## Contents * 1 Definition * 2 Signs and symptoms * 3 Causes * 4 Pathophysiology * 5 Diagnosis * 6 Treatment * 7 As an adaptation * 8 See also * 9 References * 10 External links ## Definition[edit] Maximum dimension of the spleen on abdominal ultrasonography. The standard system for classifying splenomegaly on radiography is:[3][4] * Normal (not splenomegaly): the largest dimension is less than 11 cm * Moderate splenomegaly: the largest dimension is between 11–20 cm * Severe splenomegaly: the largest dimension is greater than 20 cm Also, a cutoff of a craniocaudal height of 13 cm is also used to define splenomegaly.[5] In addition, individual intervals have been established: 90% confidence interval of maximum spleen length by abdominal ultrasonography by height of the person[6] Height Spleen length Women Men 155 – 159 cm 6.4 – 12 cm 160 – 164 cm 7.4 - 12.2 cm 8.9 - 11.3 cm 165 – 169 cm 7.5 – 11.9 cm 8.5 – 12.5 cm 170 – 174 cm 8.3 – 13.0 cm 8.6 – 13.1 cm 175 – 179 cm 8.1 – 12.3 cm 8.6 – 13.4 cm 180 – 184 cm 9.3 – 13.4 cm 185 – 189 cm 9.3 – 13.6 cm 190 – 194 cm 9.7 – 14.3 cm 195 – 199 cm 10.2 – 14.4 cm Age Cutoff[7] 3 months 6.0 cm 6 months 6.5 cm 12 months 7.0 cm 2 years 8.0 cm 4 years 9.0 6 years 9.5 cm 8 years 10.0 cm 10 years 11.0 cm 12 years 11.5 cm 15 years * 12.0 cm for girls * 13.0 cm for boys For children, the cutoffs for splenomegaly are given in this table, when measuring the greatest length of the spleen between its dome and its tip, in the coronal plane through its hilum while breathing quietly.[7] At autopsy, splenomegaly can be defined as a spleen weight above the upper limit of the standard reference range of 230 g (8.1 oz).[8][9] Splenomegaly refers strictly to spleen enlargement, and is distinct from hypersplenism, which connotes overactive function by a spleen of any size. Splenomegaly and hypersplenism should not be confused. Each may be found separately, or they may coexist. Clinically, if a spleen is palpable (felt via external examination), it means it is enlarged as it has to undergo at least twofold enlargement to become palpable. However, the tip of the spleen may be palpable in a newborn baby up to three months of age.[10] ## Signs and symptoms[edit] Symptoms may include abdominal pain, chest pain, chest pain similar to pleuritic pain when stomach, bladder or bowels are full, back pain, early satiety due to splenic encroachment, or the symptoms of anemia due to accompanying cytopenia. Signs of splenomegaly may include a palpable left upper quadrant abdominal mass or splenic rub. It can be detected on physical examination by using Castell's sign, Traube's space percussion or Nixon's sign, but an ultrasound can be used to confirm diagnosis. In patients where the likelihood of splenomegaly is high, the physical exam is not sufficiently sensitive to detect it; abdominal imaging is indicated in such patients.[11] In cases of infectious mononucleosis splenomegaly is a common symptom and health care providers may consider using abdominal ultrasonography to get insight into a person's condition.[12] However, because spleen size varies greatly, ultrasonography is not a valid technique for assessing spleen enlargement and should not be used in typical circumstances or to make routine decisions about fitness for playing sports.[12] ## Causes[edit] The most common causes of splenomegaly in developed countries are infectious mononucleosis, splenic infiltration with cancer cells from a hematological malignancy and portal hypertension (most commonly secondary to liver disease, and sarcoidosis). Splenomegaly may also come from bacterial infections, such as syphilis or an infection of the heart's inner lining (endocarditis).[13] Splenomegaly also occurs in mammals parasitized by Cuterebra fontinella.[14] The possible causes of moderate splenomegaly (spleen <1000 g) are many, and include: Splenomegaly grouped on the basis of the pathogenic mechanism Increased function Abnormal blood flow Infiltration Removal of defective RBCs * spherocytosis * thalassemia * hemoglobinopathies * nutritional anemias * early sickle cell anemia Immune hyperplasia Response to infection (viral, bacterial, fungal, parasitic) * mononucleosis, AIDS,[15] viral hepatitis * subacute bacterial endocarditis, bacterial sepsis * splenic abscess, typhoid fever * brucellosis, leptospirosis, tuberculosis * histoplasmosis * malaria, leishmaniasis, trypanosomiasis * ehrlichiosis[16] Disordered immunoregulation * rheumatoid arthritis, including cases of Felty's syndrome * systemic lupus erythematosus * serum sickness * familial hemophagocytic lymphohistiocytosis * autoimmune hemolytic anemia * autoimmune lymphoproliferative syndrome, an autosomal dominant disorder * sarcoidosis * drug reactions Extramedullary hematopoiesis * myelofibrosis * marrow infiltration by tumors, leukemias * marrow damage by radiation, toxins Organ Failure * cirrhosis Vascular * hepatic vein obstruction * portal vein obstruction * Budd–Chiari syndrome * splenic vein obstruction Infections * hepatic schistosomiasis * hepatic echinococcosis Metabolic diseases * Gaucher disease * Niemann–Pick disease * alpha-mannosidosis * Hurler syndrome and other mucopolysaccharidoses[17] * amyloidosis * Tangier disease Benign and malignant “infiltrations” * leukemias (acute, chronic, lymphoid, and myeloid) * lymphomas (Hodgkins and non-Hodgkin's) * myeloproliferative disease * metastatic tumors (commonly melanoma) * histiocytosis X * hemangioma, lymphangioma * splenic cysts * hamartomas * eosinophilic granuloma * littoral cell angioma[18][19][20] Normal spleen (in green) The causes of massive splenomegaly (spleen >1000 g) are * chronic myelogenous leukemia * myelofibrosis * malaria * splenic marginal zone lymphoma ## Pathophysiology[edit] Splenomegaly can be classified based on its pathophysiologic mechanism: * Congestive, by pooled blood (e.g., portal hypertension) * Infiltrative, by invasion by cells foreign to the splenic environment (e.g., metastases, myeloid neoplasms, lipid storage diseases) * Immune, by an increase in immunologic activity and subsequent hyperplasia (e.g., endocarditis, sarcoidosis, rheumatoid arthritis) * Neoplastic, when resident immune cells originate a neoplasm (e.g., lymphoma). [1] ## Diagnosis[edit] Abdominal CT is the most accurate. ## Treatment[edit] If the splenomegaly underlies hypersplenism, a splenectomy is indicated and will correct the hypersplenism. However, the underlying cause of the hypersplenism will most likely remain; consequently, a thorough diagnostic workup is still indicated, as, leukemia, lymphoma and other serious disorders can cause hypersplenism and splenomegaly. After splenectomy, however, patients have an increased risk for infectious diseases. Patients undergoing splenectomy should be vaccinated against Haemophilus influenzae, Streptococcus pneumoniae, and Meningococcus. They should also receive annual influenza vaccinations. Long-term prophylactic antibiotics may be given in certain cases. ## As an adaptation[edit] An enlarged spleen may be an inherited, adaptive trait selected in populations that need extra oxygen carry capacity such as deep sea divers.[21][22] ## See also[edit] * Asplenia * Hepatosplenomegaly * Portal hypertension * Sign (medicine) * Splenic infarction * Tropical splenomegaly syndrome ## References[edit] 1. ^ a b Chapman, J; Azevedo, AM (2018), "article-29386", Splenomegaly, Treasure Island (FL): StatPearls Publishing, PMID 28613657, retrieved 2019-02-26 2. ^ Ghazi, Ali (2010). "Hypercalcemia and huge splenomegaly presenting in an elderly patient with B-cell non-Hodgkin's lymphoma: a case report". Journal of Medical Case Reports. 4 (334): 330. doi:10.1186/1752-1947-4-330. PMC 2974746. PMID 20959010. 3. ^ Neetu Radhakrishnan. "Splenomegaly". Medscape. Retrieved February 16, 2018. Updated Apr. 2012 (referring the classification system to Poulin et al. 4. ^ Page 1964 in: Florian Lang (2009). Encyclopedia of Molecular Mechanisms of Disease. Springer Science & Business Media. ISBN 9783540671367. 5. ^ Saboo, S S; Krajewski, K M; O'Regan, K N; Giardino, A; Brown, J R; Ramaiya, N; Jagannathan, J P (2012). "Spleen in haematological malignancies: spectrum of imaging findings". The British Journal of Radiology. 85 (1009): 81–92. doi:10.1259/bjr/31542964. ISSN 0007-1285. PMC 3473934. PMID 22096219. 6. ^ Chow, Kai Uwe; Luxembourg, Beate; Seifried, Erhard; Bonig, Halvard (2016). "Spleen Size Is Significantly Influenced by Body Height and Sex: Establishment of Normal Values for Spleen Size at US with a Cohort of 1200 Healthy Individuals". Radiology. 279 (1): 306–313. doi:10.1148/radiol.2015150887. ISSN 0033-8419. PMID 26509293. 7. ^ a b Rosenberg, H K; Markowitz, R I; Kolberg, H; Park, C; Hubbard, A; Bellah, R D (1991). "Normal splenic size in infants and children: sonographic measurements". American Journal of Roentgenology. 157 (1): 119–121. doi:10.2214/ajr.157.1.2048509. ISSN 0361-803X. PMID 2048509. 8. ^ Molina, D. Kimberley; DiMaio, Vincent J.M. (2012). "Normal Organ Weights in Men". The American Journal of Forensic Medicine and Pathology. 33 (4): 368–372. doi:10.1097/PAF.0b013e31823d29ad. ISSN 0195-7910. PMID 22182984. 9. ^ Molina, D. Kimberley; DiMaio, Vincent J. M. (2015). "Normal Organ Weights in Women". The American Journal of Forensic Medicine and Pathology. 36 (3): 182–187. doi:10.1097/PAF.0000000000000175. ISSN 0195-7910. PMID 26108038. 10. ^ Pelizzo, G.; Guazzotti, M.; Klersy, C.; Nakib, G.; Costanzo, F.; Andreatta, E.; Bassotti, G.; Calcaterra, V. (2018). "Spleen size evaluation in children: Time to define splenomegaly for pediatric surgeons and pediatricians". PLOS ONE. 13 (8): e0202741. Bibcode:2018PLoSO..1302741P. doi:10.1371/journal.pone.0202741. PMC 6107197. PMID 30138410. 11. ^ Grover SA, Barkun AN, Sackett DL (1993). "The rational clinical examination. Does this patient have splenomegaly?". JAMA. 270 (18): 2218–21. doi:10.1001/jama.270.18.2218. PMID 8411607. Ovid full text 12. ^ a b American Medical Society for Sports Medicine (24 April 2014), "Five Things Physicians and Patients Should Question", Choosing Wisely: an initiative of the ABIM Foundation, American Medical Society for Sports Medicine, retrieved 29 July 2014, which cites * Putukian, M; O'Connor, FG; Stricker, P; McGrew, C; Hosey, RG; Gordon, SM; Kinderknecht, J; Kriss, V; Landry, G (Jul 2008). "Mononucleosis and athletic participation: an evidence-based subject review". Clinical Journal of Sport Medicine. 18 (4): 309–15. doi:10.1097/jsm.0b013e31817e34f8. PMID 18614881. * Spielmann, AL; DeLong, DM; Kliewer, MA (Jan 2005). "Sonographic evaluation of spleen size in tall healthy athletes". AJR. American Journal of Roentgenology. 184 (1): 45–9. doi:10.2214/ajr.184.1.01840045. PMID 15615949. 13. ^ Kaiser, Larry R.; Pavan Atluri; Giorgos C Karakousis; Paige M Porrett (2006). The surgical review: an integrated basic and clinical science study guide. Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-7817-5641-3. 14. ^ Durden LA (1995). "Bot Fly (Cuterebra fontinella fontinella) Parasitism of Cotton Mice (Peromyscus gossypinus) on St. Catherines Island, Georgia". The Journal of Parasitology. 81 (5): 787–790. doi:10.2307/3283977. JSTOR 3283977. 15. ^ Sproat, LO.; Pantanowitz, L.; Lu, CM.; Dezube, BJ. (Dec 2003). "Human immunodeficiency virus-associated hemophagocytosis with iron-deficiency anemia and massive splenomegaly". Clin Infect Dis. 37 (11): e170–3. doi:10.1086/379613. PMID 14614691. 16. ^ Friedman, AD.; Daniel, GK.; Qureshi, WA. (Jun 1997). "Systemic ehrlichiosis presenting as progressive hepatosplenomegaly". South Med J. 90 (6): 656–60. doi:10.1097/00007611-199706000-00017. PMID 9191748. 17. ^ Neufeld EF, Muenzer J (1995). "The mucopolysaccharidoses". In Scriver CR, Beaudet AL, Sly WS, Valle D (eds.). The metabolic and molecular bases of inherited disease.7th ed. Vol. 2. McGraw-Hill, New York. pp. 2465–94. 18. ^ Suvajdzić, N.; Cemerikić-Martinović, V.; Saranović, D.; Petrović, M.; Popović, M.; Artiko, V.; Cupić, M.; Elezović, I. (Oct 2006). "Littoral-cell angioma as a rare cause of splenomegaly". Clin Lab Haematol. 28 (5): 317–20. doi:10.1111/j.1365-2257.2006.00801.x. PMID 16999722. 19. ^ Dascalescu, CM.; Wendum, D.; Gorin, NC. (Sep 2001). "Littoral-cell angioma as a cause of splenomegaly". N Engl J Med. 345 (10): 772–3. doi:10.1056/NEJM200109063451016. PMID 11547761. 20. ^ Ziske, C.; Meybehm, M.; Sauerbruch, T.; Schmidt-Wolf, IG. (Jan 2001). "Littoral cell angioma as a rare cause of splenomegaly". Ann Hematol. 80 (1): 45–8. doi:10.1007/s002770000223. PMID 11233776. 21. ^ Rappaport, Lisa (19 April 2018). "Large spleen helps explain deep-diving skills of Southeast Asian 'sea nomads'". Reuters. Retrieved 20 April 2018. 22. ^ Ilardo, M. A.; Moltke, I.; Korneliussen, T. S.; Cheng, J.; Stern, A. J.; Racimo, F.; de Barros Damgaard, P.; Sikora, M.; Seguin-Orlando, A.; Rasmussen, S.; van den Munckhof, I. C. L.; ter Horst, R.; Joosten, L. A. B.; Netea, M. G.; Salingkat, S.; Nielsen, R.; Willerslev, E. (2018-04-18). "Physiological and Genetic Adaptations to Diving in Sea Nomads". Cell. 173 (3): 569–580.e15. doi:10.1016/j.cell.2018.03.054. PMID 29677510. ## External links[edit] * Splenomegaly and hypersplenism at patient.info Classification D * ICD-10: Q89.0, R16.1 * ICD-9-CM: 759.0, 789.2 * MeSH: D013163 * DiseasesDB: 12375 External resources * MedlinePlus: 003276 * eMedicine: ped/2139 med/2156 * v * t * e Lymphatic disease: organ and vessel diseases Thymus * Abscess * Hyperplasia * Hypoplasia * DiGeorge syndrome * Ectopic thymus * Thymoma * Thymic carcinoma Spleen * Asplenia * Asplenia with cardiovascular anomalies * Accessory spleen * Polysplenia * Wandering spleen * Splenomegaly * Banti's syndrome * Splenic infarction * Splenic tumor Lymph node * Lymphadenopathy * Generalized lymphadenopathy * Castleman's disease * Intranodal palisaded myofibroblastoma * Kikuchi disease * Tonsils * see Template:Respiratory pathology Lymphatic vessels * Lymphangitis * Lymphangiectasia * Lymphedema * Primary lymphedema * Congenital lymphedema * Lymphedema praecox * Lymphedema tarda * Lymphedema–distichiasis syndrome * Milroy's disease * Secondary lymphedema * Bullous lymphedema * Factitial lymphedema * Postinflammatory lymphedema * Postmastectomy lymphangiosarcoma * Waldmann disease * v * t * e Symptoms and signs relating to the human digestive system or abdomen Gastrointestinal tract * Nausea * Vomiting * Heartburn * Aerophagia * Pagophagia * Dysphagia * oropharyngeal * esophageal * Odynophagia * Bad breath * Xerostomia * Hypersalivation * Burping * Wet burp * Goodsall's rule * Chilaiditi syndrome * Dance's sign * Aaron's sign * Arapov's sign * Markle sign * McBurney's point * Sherren's triangle * Radiologic signs: Hampton's line * Klemm's sign Accessory * liver: Councilman body * Mallory body * biliary: Boas' sign * Courvoisier's law * Charcot's cholangitis triad/Reynolds' pentad * cholecystitis (Murphy's sign * Lépine's sign * Mirizzi's syndrome) * Nardi test Defecation * Flatulence * Fecal incontinence * Encopresis * Fecal occult blood * Rectal tenesmus * Constipation * Obstructed defecation * Diarrhea * Rectal discharge * Psoas sign * Obturator sign * Rovsing's sign * Hamburger sign * Heel tap sign * Aure-Rozanova's sign * Dunphy sign * Alder's sign * Lockwood's sign * Rosenstein's sign Abdomen Pain * Abdominal pain * Acute abdomen * Colic * Baby colic * Abdominal guarding * Blumberg sign Distension * Abdominal distension * Bloating * Ascites * Tympanites * Shifting dullness * Ascites * Fluid wave test Masses * Abdominal mass * Hepatosplenomegaly * Hepatomegaly * Splenomegaly Other * Jaundice * Mallet-Guy sign * Puddle sign * Ballance's sign * Aortic insufficiency * Castell's sign * Kehr's sign * Cullen's sign * Grey Turner's sign Hernia * Howship–Romberg sign * Hannington-Kiff sign Other * Cupola sign * Fothergill's sign * Carnett's sign * Sister Mary Joseph nodule [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: 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population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Splenomegaly	c0038002	29,858	wikipedia	https://en.wikipedia.org/wiki/Splenomegaly	2021-01-18T18:48:19	{"gard": ["7684"], "mesh": ["D013163"], "umls": ["C0038002"], "icd-9": ["789.2", "759.0"], "icd-10": ["Q89.0", "R16.1"], "wikidata": ["Q1129121"]}
Galactosialidosis Other namesNeuraminidase deficiency with beta-galactosidase deficiency[1] Lysosomes contain digestive enzymes that break down cellular waste. SpecialtyEndocrinology Galactosialidosis, also known as Neuraminidase deficiency with beta-galactosidase deficiency, is a genetic lysosomal storage disease.[2] It is caused by a mutation in the CTSA gene which leads to a deficiency of enzymes β-galactosidase and neuraminidase. This deficiency inhibits the lysosomes of cells from functioning properly, resulting in the accumulation of toxic matter within the cell. Hallmark symptoms include abnormal spinal structure, vision problems, coarse facial features, hearing impairment, and intellectual disability. Because galactosialidosis involves the lysosomes of all cells, it can affect various areas of the body, including the brain, eyes, bones, and muscles.[3] Depending on the patient's age at the onset of symptoms, the disease consists of three subtypes: early infantile, late infantile, and juvenile/adult.[4] This condition is considered rare, with most cases having been in the juvenile/adult group of patients. ## Contents * 1 Signs and Symptoms * 2 Causes * 2.1 Molecular Biology * 2.2 Genetic Inheritance * 3 Mechanism of Disease * 4 Diagnosis * 5 Prevention and Treatment * 6 Prognosis * 6.1 Early infantile * 6.2 Late infantile * 6.3 Juvenile/adult * 7 Epidemiology * 8 Research * 9 References * 10 External links ## Signs and Symptoms[edit] The signs and symptoms of galactosialidosis range from mild to severe, and can vary amongst patients depending on the age of the individual when symptoms begin as well as the specific subtype of disease each person has.[4] Symptoms can also vary amongst individuals within the same subtype, but it is known that the earlier a person shows symptoms, the more severe the disease tends to progress over time. Individuals who are diagnosed with early infantile galactosialidosis have symptoms which present just before or after birth and tend to be most severe. The most common symptoms include abnormal fluid build up, hepatosplenomegaly, enlarged heart, abnormal bone development, kidney disease that progressively worsens, coarse facial features, and a cherry red spot on the back of the eye.[3] Those who are diagnosed with late infantile subtype have symptoms which are similar to early infantile, except that they present around 6 months of age and tend to be less severe. Additional symptoms in this subtype can include growth problems, hearing or vision problems, and seizures.[3] Juvenile/adult subtype symptoms include impaired balance or coordination, dark red spots on the skin or angiokeratomas, vision loss, seizures, and muscle jerks or myoclonus. The symptoms of this subtype tend to be less severe than the first two subtypes, and typically start in adolescence, with the average age being 16 years of age.[5] Molecular structure of the enzyme Cathepsin A. Molecular structure of the enzyme neuraminidase-1 (NEU1). ## Causes[edit] ### Molecular Biology[edit] Galactosialidosis is caused by a mutation in the CTSA gene. This gene encodes the enzyme cathepsin A,[6] which forms a protein complex with neuraminidase-1 and beta-galactosidase to break down fats, sugars, and proteins ingested by lysosomes.[4] Cathepsin A is required in this process because within the complex, it prevents neuraminidase-1 and beta-galactosidase from breaking down prematurely, so that they may perform their functions properly. When the CTSA gene is mutated, the protein structure of cathepsin A is defected, making it incapable of binding to other proteins or form complexes. This leads to a deficiency of beta-galactosidase (GLB1) and neuraminidase-1 (NEU1).[7] As a result, the lysosome is unable to break down toxic substances and waste builds up within the cell. Molecular structure of the enzyme beta-galatosidase. ### Genetic Inheritance[edit] All individuals diagnosed with galactosialidosis have inherited the condition in an autosomal recessive manner, regardless of age or subtype. All genes consists of two copies, one received from each parent. When a disease is recessive , it means that two mutated copies of a gene are required for someone to inherit the trait or disorder.[8] When each parent carries one mutated copy of the same gene, there is a 25% possibility that their offspring will inherit both copies of the gene and develop the disease. In galactosialidosis, both parents of the patient would have carried a mutated copy of the CTSA gene. The affected child inherits both copies, leading to the development of the disease. There are no known environmental or medical associations related to the cause of galactosialidosis. Galactosialidosis is inherited in an autosomal recessive manner, and requires both parents to be carriers of the mutated gene. ## Mechanism of Disease[edit] Galactosialidosis occurs when a patient inherits two copies of a mutated CTSA gene. Encoding of the mutated gene results in a defective form of the protein cathepsin A. When the structure of cathepsin A is disrupted due to mutation, it becomes non-functional and cannot form a digestive complex with neuraminidase-1 and beta-galactosidase. As a result, toxic materials accumulate within the cells of the body due to the lysosomes' inability to perform its functions.[4] ## Diagnosis[edit] When the characteristic symptoms of galactosialidosis are suspected, patients can undergo specific testing to confirm their diagnosis. One common method includes enzyme assays which measure the activity of neuraminidase-1 and beta-galactosidase.[4] Decreased levels in enzymatic activity indicate a deficiency in cathepsin A. A complete urinalysis can be performed to detect the presence of oligosaccharides,[4] which would pass through the urine as excess amounts accumulate within cells due to lysosomal dysfunction. A diagnosis can more specifically be confirmed through molecular genetic analysis, which is used to identify a mutation in the CTSA gene. Once a mutation is detected, the results are combined with a clinical exam and patient symptoms to fully diagnosis galactosialidosis.[3] The age of the patient at the onset of symptoms is used to determine the specific disease subtype of the patient:[3] early infantile patients are diagnosed between birth and 3 months of age, late infantile patients are diagnosed between 3-12 months of age, and juvenile/adult patients are normally diagnosed in adolescence when symptoms begin.[9] A prenatal diagnosis was made by Kleijer et al. in 1979 by measuring beta-galactosidase and neuraminidase activities in cultured amniotic fluid cells.[10] ## Prevention and Treatment[edit] Currently, there is no cure for galactosialidosis. However, there are treatments available that help to manage symptoms and provide supportive care.[9] For example, a treatment plan may include medications to control seizures or muscle jerks. It is also common for patients to establish routine care with a medical geneticist, neurologist, and ophthalmologist[3] depending on the symptoms they are experiencing and the frequency at which they occur. Because the disease is genetically inherited, the only prevention available for this condition is through genetic carrier screening that can detect the presence of a recessive, mutated CTSA gene in parents before they decide to have children. If both parents are found to be carriers of the mutated gene, there will be a 25% possibility of the child inheriting the disease; this cannot be prevented. ## Prognosis[edit] The prognosis of individuals diagnosed with galactosialidosis vary between patients, depending on age and severity of symptoms. Therefore, there is no established average age at which patients die or have increased risk of death. There is no chance of full recovery in any form of the disease. ### Early infantile[edit] Patients diagnosed with early infantile subtype have more severe, threatening symptoms and a decreased chance of survival because this subtype develops more rapidly,[4] however it is noted that most patients do live into late infancy.[9] ### Late infantile[edit] Because patients with late infantile subtype develop symptoms within the first year of life, their condition is not as severe as early infantile subtype and the chance of survival is higher, however the quality of life for the patient will still be greatly affected due to the fact that the patient is so young when symptoms occur. The patient will still require a detailed care plan to manage symptoms.[3] ### Juvenile/adult[edit] Patients diagnosed with juvenile/adult subtype have less severity of symptoms, but will have to manage progressive mental disability, spinal deformities, and seizures amongst other common symptoms. However, this subtype is typically associated with a normal life expectancy.[9] ## Epidemiology[edit] Galactosialidosis is considered a very rare disease, though the prevalence of it is not exactly known. Less than 150 cases have been reported in literature; of that population, about 60% of cases were of the juvenile/adult subtype[5] with symptoms beginning at or after 16 years of age. It is also documented that most cases occur in people of Japanese descent.[3] ## Research[edit] There is a current need for future research that leads to a better understanding of galactosialidosis, advances in diagnoses, and more effective treatment. More recent research has been done to define the demographics and clinical characteristics of the patient population with galactosialidosis, with the ultimate goal of using this information toward a gene transfer treatment study.[11] There are currently at least two ongoing clinical trials for galactosialidosis. One study involves research of the glycoproteinoses that constitute some of the rarest lysosomal diseases, including galactosialidosis, aspartylglucosaminuria, fucosidosis, Schindler disease, and sialidosis amongst other diseases. It is a longitudinal study of 100 patients who are diagnosed with any one of nine glycoproteinoses. The purpose of the study is to better define how common the diseases are, identify clinical features that could contribute to early diagnoses, detail progression of the diseases, assess the supportive therapies currently being used, and identify possible treatments.[12] ## References[edit] 1. ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Galactosialidosis". www.orpha.net. Retrieved 11 April 2019. 2. ^ Koike K, Hamaguchi T, Kitamura H, Imasawa T, Joh K (2008). "Galactosialidosis associated with IgA nephropathy: morphological study of renal biopsy". Pathol. Int. 58 (5): 295–9. doi:10.1111/j.1440-1827.2008.02226.x. PMID 18429828. 3. ^ a b c d e f g h "Galactosialidosis \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2020-10-14. 4. ^ a b c d e f g "Galactosialidosis". Rare Genomics Institute. Retrieved 2020-10-14. 5. ^ a b "Galactosialidosis: MedlinePlus Genetics". medlineplus.gov. Retrieved 2020-11-11. 6. ^ Kleijer WJ, Geilen GC, Janse HC, et al. (1996). "Cathepsin A deficiency in galactosialidosis: studies of patients and carriers in 16 families". Pediatr. Res. 39 (6): 1067–71. doi:10.1203/00006450-199606000-00022. PMID 8725271. 7. ^ Caciotti A, Catarzi S, Tonin R, Lugli L, Perez CR, Michelakakis H, Mavridou I, Donati MA, Guerrini R, D'Azzo A, Morrone A (2013). "Galactosialidosis: review and analysis of CTSA gene mutations". Orphanet J Rare Dis. 8 (1): 114. doi:10.1186/1750-1172-8-114. PMC 3737020. PMID 23915561. 8. ^ "Autosomal Recessive Inheritance". www.stlouischildrens.org. Retrieved 2020-11-11. 9. ^ a b c d "Galactosialidosis". ISMRD. Retrieved 2020-11-11. 10. ^ Kleijer, W. J.; Hoogeveen, A.; Verheijen, F. W.; Niermeijer, M. F.; Galjaard, H.; O'Brien, J. S.; Warner, T. G. (July 1979). "Prenatal diagnosis of sialidosis with combined neuraminidase and beta-galactosidase deficiency". Clinical Genetics. 16 (1): 60–61. doi:10.1111/j.1399-0004.1979.tb00851.x. ISSN 0009-9163. PMID 477017. 11. ^ "Characterization of the Patient Population With Galactosialidosis - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Retrieved 2020-11-11. 12. ^ Greenwood Genetic Center (2017-07-31). "Longitudinal Studies of the Glycoproteinoses". Cite journal requires `\|journal=` (help) ## External links[edit] * Neuraminidase deficiency with beta-galactosidase deficiency at NIH's Office of Rare Diseases Classification D * ICD-10: E77.1 * OMIM: 256540 * MeSH: C536411 * DiseasesDB: 33441 External resources * Orphanet: 351 * v * t * e Lysosomal storage diseases: Inborn errors of carbohydrate metabolism (Glycoproteinoses) Anabolism * Dolichol kinase deficiency * Congenital disorder of glycosylation Post-translational modification of lysosomal enzymes * Mucolipidosis: I-cell disease (ML II) * Pseudo-Hurler polydystrophy (ML III) Catabolism * Aspartylglucosaminuria * Fucosidosis * mannosidosis * Alpha-mannosidosis * Beta-mannosidosis * Sialidosis * Schindler disease Other * solute carrier family (Salla disease) * Galactosialidosis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Galactosialidosis	c0268233	29,859	wikipedia	https://en.wikipedia.org/wiki/Galactosialidosis	2021-01-18T18:44:40	{"gard": ["3953"], "mesh": ["C536411"], "umls": ["C0268233"], "icd-10": ["E77.1"], "orphanet": ["351"], "wikidata": ["Q1491661"]}
Karnataka liquor deaths are deaths in Karnataka state in India in 1981 by consuming illegal liquor. In July 1981 about 308 people died in Bangalore by illicit liquor.[1] Adulteration of cheap liquor by methyl alcohol resulted in deaths.[specify] Availability of cheap spurious alcohol, (known as hooch) is a problem around the Tannery Road area of the Bangalore Cantonment, with many dwellers getting addicted. Notorious bootlegger Marimuthu (who later became a councillor of BBMP) and Ameer Jan were running the racket. Hooch is brewed from industrial alcohol, by separating Methyl Alcohol, and adding water - A dangerous process which can leave traces of poisonous Methyl Alcohol. The brew is slow poison, damaging kidney and intestines, leading to slow death. On 7 July 1981, about 300 people (Official figures 229) around the Tannery Road area died as a result of consuming this spurious alcohol. Most of the victims were poor Dalits. Police registered cases against 63 people, but none were convicted or punished. An enquiry commission revealed a connection between some politicians and the bootleggers. A paltry sum of INR 1000 per family was paid to the victims by the Gundu Rao government.[2] ## See also[edit] List of alcohol poisonings in India ## References[edit] 1. ^ "Deaths From Illegal Liquor Rise to 308 in Southern India". The New York Times. 10 July 1981. Retrieved 5 July 2010. 2. ^ Hanumantharaya, C H (14 December 2012). "The Big Hooch Tragedy" (Bangalore). Talk. Archived from the original on 4 January 2015. Retrieved 4 January 2015. This Indian history-related article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Karnataka alcohol poisonings	None	29,860	wikipedia	https://en.wikipedia.org/wiki/Karnataka_alcohol_poisonings	2021-01-18T18:58:41	{"wikidata": ["Q4579864"]}
Dermatoosteolysis, Kirghizian type, is characterised by recurrent skin ulceration, arthralgia, fever, peri-articular osteolysis, oligodontia and nail dystrophy. This disease has been described in five sibs in a family of Kirghizian origin (Central Asia). Three of the sibs also presented with keratitis leading to visual impairment or blindess. Transmission is autosomal recessive. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Dermatoosteolysis, Kirghizian type	c1857301	29,861	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1657	2021-01-23T18:44:47	{"gard": ["1814"], "mesh": ["C535373"], "omim": ["221810"], "umls": ["C1857301"]}
Neuropathy, ataxia, and retinitis pigmentosa (NARP) is a condition that causes a variety of signs and symptoms that mainly affect the nervous system. The condition typically begins in childhood or early adulthood, and the signs and symptoms usually worsen over time. Most people with NARP experience numbness, tingling, or pain in the arms and legs (sensory neuropathy); muscle weakness; and problems with balance and coordination (ataxia). Many affected individuals also have vision loss caused by changes in the light-sensitive tissue that lines the back of the eye (the retina). In some cases, the vision loss results from a condition called retinitis pigmentosa. This eye disease causes the light-sensing cells of the retina gradually to deteriorate. Learning disabilities and developmental delays are often seen in children with NARP, and older individuals with this condition may experience a loss of intellectual function (dementia). Other features of NARP include seizures, hearing loss, and abnormalities of the electrical signals that control the heartbeat (cardiac conduction defects). These signs and symptoms vary among affected individuals. ## Frequency The prevalence of NARP is unknown. This disorder is probably less common than a similar but more severe condition, Leigh syndrome, which affects about 1 in 40,000 people. ## Causes NARP results from mutations in the MT-ATP6 gene. This gene is contained in mitochondrial DNA, also known as mtDNA. Mitochondria are structures within cells that convert the energy from food into a form that cells can use. Although most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA, known as mitochondrial DNA or mtDNA. The MT-ATP6 gene provides instructions for making a protein that is essential for normal mitochondrial function. Through a series of chemical reactions, mitochondria use oxygen and simple sugars to create adenosine triphosphate (ATP), the cell's main energy source. The MT-ATP6 protein forms one part (subunit) of an enzyme called ATP synthase, which is responsible for the last step in ATP production. Mutations in the MT-ATP6 gene alter the structure or function of ATP synthase, reducing the ability of mitochondria to make ATP. It remains unclear how this disruption in mitochondrial energy production leads to muscle weakness, vision loss, and the other specific features of NARP. ### Learn more about the gene and chromosome associated with Neuropathy, ataxia, and retinitis pigmentosa * MT-ATP6 * mitochondrial dna ## Inheritance Pattern This condition is inherited in a mitochondrial pattern, which is also known as maternal inheritance. This pattern of inheritance applies to genes contained in mtDNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, children can inherit disorders resulting from mtDNA mutations only from their mother. These disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass traits associated with changes in mtDNA to their children. Most of the body's cells contain thousands of mitochondria, each with one or more copies of mtDNA. The severity of some mitochondrial disorders is associated with the percentage of mitochondria in each cell that has a particular genetic change. Most individuals with NARP have a specific MT-ATP6 mutation in 70 percent to 90 percent of their mitochondria. When this mutation is present in a higher percentage of a person's mitochondria—more than 90 percent to 95 percent—it usually causes a more severe condition known as maternally inherited Leigh syndrome. Because these two conditions result from the same genetic changes and can occur in different members of a single family, and because some individuals with MT-ATP6 gene mutations have related signs and symptoms that do not follow the specific patterns of these conditions, researchers believe that the conditions may be part of a spectrum of overlapping features rather than two distinct syndromes. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Neuropathy, ataxia, and retinitis pigmentosa	c1328349	29,862	medlineplus	https://medlineplus.gov/genetics/condition/neuropathy-ataxia-and-retinitis-pigmentosa/	2021-01-27T08:25:08	{"gard": ["262"], "mesh": ["C537396"], "omim": ["551500"], "synonyms": []}
Infantile spasms-broad thumbs syndrome is a rare neurologic disorder characterized by profound developmental delay, facial dysmorphism (i.e. microcephaly, large anterior fontanel, hypertelorism, downslanting palpebral fissures, beaked nose, micrognathia), broad thumbs and flexion and/or extension spasms. Bilateral cataracts, hypertrophic cardiomyopathy and hydrocele have also been reported. EEG shows hypsarrhythmic features and MRI may reveal partial agenesis of the corpus callosum, mild brain atrophy and/or ventriculomegaly. There have been no further descriptions in the literature since 1990. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Infantile spasms-broad thumbs syndrome	None	29,863	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3173	2021-01-23T17:49:43	{"gard": ["3002"], "icd-10": ["G40.4"], "synonyms": ["Tsao-Ellingson syndrome"]}
## Description Fetal cystic hygromas are congenital malformations of the lymphatic system appearing as single or multiloculated fluid-filled cavities, most often in the neck. They are thought to arise from failure of the lymphatic system to communicate with the venous system in the neck. They often progress to hydrops and cause fetal death (Chervenak et al., 1983). Clinical Features Bieber et al. (1979) reported a sibship in which the first and third pregnancies ended in stillborn female infants with a 'bag of water' at the nape of the neck. The mother sought genetic counseling in relation to the fourth pregnancy. Ultrasonography suggested occipital encephalocele, and alpha-1-fetoprotein (AFP; 104150) was greatly elevated. Elective abortion was performed at 21 weeks of gestation. The fetus had a normal 46,XX karyotype and a large nuchal bleb with no evidence of encephalocele. Nuchal bleb in the XO Turner syndrome is also accompanied by elevation of AFP in the amniotic fluid. Chervenak et al. (1983) studied 15 consecutive cases of nuchal hygroma detected prenatally. None survived. In 11, the karyotype was consistent with the Turner syndrome and another probably had XY gonadal dysgenesis. Three had a 46,XX karyotype and 2 of these had multiple malformations. Watson et al. (1990) reported a 29-year-old white female who had consecutive pregnancies in which the fetus was found to have cystic hygroma with hydrops. In 2 of the fetuses, a normal karyotype was documented. Dallapiccola et al. (1984) described a similar patient who had 2 consecutive fetuses with cystic hygroma, both with a normal karyotype. Williams and Josephson (1997) described an Amish family in which 2 brothers had isolated cystic hygroma. A second Amish family had 2 children, a boy and a girl, with congenital chylothorax; both died as a consequence of this condition, one prenatally and one neonatally. The authors stated that familial cystic hygroma not associated with hydrops fetalis and neonatal death had not previously been reported. By ultrasound examinations, Bruni et al. (1999) detected nuchal cystic hygroma and nonimmune hydrops fetalis (236750) in 2 male sibs. Fetal and parental karyotypes were normal. The parents were consanguineous. The parents elected to terminate the 2 pregnancies. Postmortem examination showed no anomalies other than those detected by ultrasound. Autosomal recessive inheritance of this combination of abnormalities was suggested by the observations. Inheritance Although cystic hygroma is a conspicuous feature of the Turner syndrome and may occur in some mendelian disorders, its occurrence as an isolated autosomal recessive has been suggested by several reports (e.g., Watson et al., 1990 and Williams and Josephson, 1997). History Gobbel et al. (2007) identified 5 human fetuses with severe cystic hygroma in the Meckel anatomic collection at the University of Halle Medical School in Germany. The cases had been described by Meckel the Younger in 1826 and 1 of his students in 1819. The fetuses were between 13 and 17 weeks' gestational age. Radiographic techniques confirmed the diagnoses and comparative genomic hybridization showed normal chromosome number. Gobbel et al. (2007) also provided an historical review of the collection and the work of J. F. Meckel the Younger, who lived from 1781 to 1833. Misc \- Fetal hydrops \- Fetal death Neck \- Nuchal bleb \- Fetal cystic hygroma Lab \- Normal karyotype \- High amniotic fluid AFP Inheritance \- Autosomal recessive \- more often 45,X Turner syndrome ▲ 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	NUCHAL BLEB, FAMILIAL	c0206620	29,864	omim	https://www.omim.org/entry/257350	2019-09-22T16:24:11	{"doid": ["3081"], "mesh": ["D018191"], "omim": ["257350"], "orphanet": ["79486"], "synonyms": ["Alternative titles", "CYSTIC HYGROMA, FETAL"]}
A benign congenital skin disease characterised by progressive dilation of the subepidermal skin vessels manifesting as purple punctate lesions usually appearing on the lower limbs and buttocks and following the lines of Blaschko. ## Epidemiology The disease occurs almost exclusively in females. ## Etiology A mutation in the Xp11.3-Xq12 region has been identified in one of the reported families. However, in this family the AS was associated with oesophageal papillomatosis leading to the suggestion that this case of familial AS represents a mild form of focal dermal hypoplasia (see this term). ## Genetic counseling The majority of cases are sporadic. Only a few familial cases have been reported in the literature so far and transmission may be autosomal dominant or X-linked. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Angioma serpiginosum	c1970130	29,865	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=95429	2021-01-23T17:35:31	{"mesh": ["C536365"], "omim": ["106050", "300652"], "icd-10": ["L81.7"]}
A number sign (#) is used with this entry because of evidence that congenital bile acid synthesis defect-3 (CBAS3) is caused by homozygous mutation in the CYP7B1 gene (603711) on chromosome 8q12. For a general phenotypic description and a discussion of genetic heterogeneity of congenital bile acid synthesis defects, see 607765. Clinical Features Setchell et al. (1998) described an inborn error of bile acid synthesis involving a deficiency in 7-alpha-hydroxylation in a male offspring of first-cousin Mexican parents. The patient developed jaundice at 6 days of age, which resolved with phototherapy. During week 6 of life he intermittently passed acholic stools; jaundice returned at 8 weeks of age. Other features included hepatosplenomegaly and increased bleeding. Serum AST, ALT, and alkaline phosphatase enzymes were markedly elevated and prothrombin time was prolonged. Percutaneous liver biopsy showed marked increase in portal connective tissue with bridging fibrosis and probable cirrhosis, as well as mild portal inflammation and moderate lobular disarray with giant cell transformation. After transient treatment with oral cholic acid, he underwent liver transplantation. The diagnosis was established by fast atom bombardment, ionization-mass spectrometry, which revealed elevated urinary bile acid excretion, a mass spectrum with intense ions at m/z 453 and m/z 510 corresponding to sulfate and glycosulfate conjugates of unsaturated monohydroxycholenoic acids, and an absence of primary bile acids. Levels of 27-hydroxycholesterol were more than 4,500 times normal. Hepatic microsomal oxysterol 7-alpha-hydroxylase activity was undetectable. It was thought that an accumulation of hepatotoxic unsaturated monohydroxy bile acids accounted for the pathology. Setchell et al. (1998) stated that more than 2,500 samples from cholestatic infants had been analyzed by mass spectrometry between 1988 and 1998 at Children's Hospital in Cincinnati, and that this was the first patient identified with deficiency in 7-alpha-hydroxylation of bile acids. They speculated that the relatively early age of the patient and the severity of the liver disease may indicate that a mutation in the oxysterol 7-alpha-hydroxylase gene causes prenatal or early neonatal lethality, and that this case represents an exception to fetal death. Molecular Genetics In a child with congenital bile acid synthesis defect-3, Setchell et al. (1998) identified a homozygous nonsense mutation in the CYP7B1 gene (R388X; 603711.0001). INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive ABDOMEN External Features \- Intrahepatic cholestasis \- Jaundice \- Hepatomegaly \- Giant cell hepatitis seen on biopsy \- Nonspecific inflammation seen on biopsy \- Fibrosis seen on biopsy \- Cirrhosis \- Progressive liver failure Spleen \- Splenomegaly Gastrointestinal \- Diarrhea \- Steatorrhea \- Discolored, acholic stools \- Malabsorption of fat and fat-soluble vitamins SKIN, NAILS, & HAIR Skin \- Jaundice HEMATOLOGY \- Coagulopathy secondary to liver disease LABORATORY ABNORMALITIES \- Increased serum bilirubin \- Abnormal liver function tests \- Increased alkaline phosphatase MISCELLANEOUS \- Neonatal onset \- Caused by inborn error in bile acid synthesis \- One patient has been reported (as of March 2011) MOLECULAR BASIS \- Caused by mutation in the cytochrome P450, family 7, subfamily B, polypeptide 1 gene (CYP7B1, 603711.0001 ) ▲ 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	BILE ACID SYNTHESIS DEFECT, CONGENITAL, 3	c3151147	29,866	omim	https://www.omim.org/entry/613812	2019-09-22T15:57:19	{"doid": ["0111070"], "mesh": ["C566340"], "omim": ["613812"], "orphanet": ["79302"]}
A number sign (#) is used with this entry because of evidence that primary ciliary dyskinesia-17 (CILD17) is caused by homozygous mutation in the CCDC103 gene (614677) on chromosome 17q21. Description Primary ciliary dyskinesia-17 is an autosomal recessive disorder characterized by early infantile onset of respiratory distress associated with a defect in the function of ciliary outer dynein arms. Situs inversus is variable (summary by Panizzi et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of primary ciliary dyskinesia, see CILD1 (244400). Clinical Features Panizzi et al. (2012) reported 10 patients from 6 families with primary ciliary dyskinesia. Five of the families were consanguineous and of Pakistani origin, and 1 was nonconsanguineous and of German origin. Four of the Pakistani families had previously been reported by O'Callaghan et al. (2010) and resided in the U.K. The patients had classic features of the disorder, including recurrent upper and lower respiratory infections, sinusitis, bronchiectasis, and variable dextrocardia or situs inversus. Electron microscopy showed variable defects in the inner and outer dynein arms of cilia that differed even with a family. Videomicroscopy showed either complete cilia paralysis, reduced beat amplitude, or loss of beat coordination. Inheritance The transmission pattern of CILD17 in the families reported by Panizzi et al. (2012) was consistent with autosomal recessive inheritance. Mapping By whole-genome linkage analysis of 4 consanguineous Pakistani families with CILD and absent outer and inner dynein arms, Panizzi et al. (2012) identified a locus on chromosome 17q12-q22 (maximum lod score of 4.8). The candidate region spanned 14 cM. Molecular Genetics In 10 patients from 6 families with CILD17, Panizzi et al. (2012) identified 1 of 2 homozygous mutations in the CCDC103 gene: 383delG (614677.0001) or H154P (614677.0002). INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Chronic sinusitis Ears \- Chronic otitis Nose \- Chronic rhinitis CARDIOVASCULAR Heart \- Dextrocardia (in some) RESPIRATORY \- Recurrent cough \- Recurrent respiratory infections Lung \- Bronchiectasis ABDOMEN \- Situs inversus (in some patients) LABORATORY ABNORMALITIES \- Immotile or weakly motile cilia \- Loss of ciliary beat coordination \- Inner and outer dynein arm defects, variable MISCELLANEOUS \- Onset at birth MOLECULAR BASIS \- Caused by mutation in the coiled-coil domain-containing protein 103 (CCDC103, 614677.0001 ) ▲ 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	CILIARY DYSKINESIA, PRIMARY, 17	c3542550	29,867	omim	https://www.omim.org/entry/614679	2019-09-22T15:54:33	{"doid": ["0110621"], "omim": ["614679", "244400"], "orphanet": ["244"], "synonyms": ["Alternative titles", "PCD", "CILIARY DYSKINESIA, PRIMARY, 17, WITH OR WITHOUT SITUS INVERSUS"], "genereviews": ["NBK1122"]}
A number sign (#) is used with this entry because familial atypical multiple mole melanoma-pancreatic carcinoma (FAMMPC) syndrome can be caused by mutations in the gene encoding cyclin-dependent kinase inhibitor-2A (CDKN2A; 600160). Description Melanoma-pancreatic cancer syndrome is an inherited cancer predisposition syndrome in which mutation carriers have an increased risk of developing malignant melanoma and/or pancreatic cancer. Mutation carriers within families may develop either or both types of cancer (summary by Harinck et al., 2012). For background and phenotypic information on malignant melanoma and pancreatic cancer, see 155600 and 260350, respectively. Molecular Genetics Whelan et al. (1995) described a kindred with an increased risk of pancreatic cancers, melanomas, and possibly additional types of tumors cosegregating with the CDKN2A gly93-to-trp mutation (G93W; 600160.0005). Of interest was the occurrence of squamous-cell carcinomas in this family, a rare form, and squamous cell carcinoma of the tongue in the proband. Goldstein et al. (1995) also showed that pancreatic carcinoma was found within melanoma families in individuals carrying CDKN2A mutations. Schutte et al. (1997) showed that almost all pancreatic carcinomas have inactivation of the CDKN2A gene. Vasen et al. (2000) performed mutation analysis on 27 families with FAMMM syndrome and identified the CDKN2A-Leiden mutation (600160.0003) in 19 families. They identified 86 patients with melanoma, and the second most frequent cancer was pancreatic carcinoma, which was observed in 15 patients from 7 families. The mean age at diagnosis of pancreatic carcinoma was 58 years, with a range from 38 to 77 years. Putative mutation carriers had an estimated cumulative risk of 17% for developing pancreatic carcinoma by age 75 years. In the 8 CDKN2A-Leiden-negative families, no cases of pancreatic carcinoma had occurred. The authors concluded that individuals with the CDKN2A-Leiden mutation show an enormous risk of developing pancreatic cancer. Lynch et al. (2002) described 8 families with what they termed the FAMMMPC syndrome who had mutations in the CDKN2A gene. They stated that the Creighton University registry of familial pancreatic cancer had 159 families, of which 19 (12%) showed the FAMMM cutaneous phenotype. Harinck et al. (2012) identified CDKN2A mutations in 6 (21%) of 28 families ascertained for familial clustering of pancreatic cancer. Five of the 6 families were of Caucasian origin and carried the same Dutch founder mutation (19-bp del; 600160.0003). Four of the 5 families with the Leiden mutation had members who developed melanoma. In the fifth family, only pancreatic cancer segregated with mutation status. A sixth family, of Indonesian origin, with only pancreatic cancer and no melanoma carried a different heterozygous mutation in the CDKN2A gene (600160.0022). Harinck et al. (2012) concluded that the CDKN2A gene should be analyzed in families with pancreatic cancer, even if melanoma is not present. Population Genetics In a population-based study, Ghiorzo et al. (2012) identified CDKN2A mutations in 13 (5.7%) of 225 Italian patients with pancreatic cancer. Six patients carried the common G101W mutation (600160.0005), which was the most common mutation. Among the 16 probands with a family history of cancer, including pancreatic cancer and melanoma, 5 (31%) were found to carry CDKN2A mutations. The mutation frequency ranged from 20% in families with 2 affected members to 50% in families with 3 affected members. The findings suggested that CDKN2A is the main susceptibility gene in Italian families with pancreatic cancer. INHERITANCE \- Autosomal dominant NEOPLASIA \- Pancreatic adenocarcinoma \- Pancreatic squamous cell carcinoma \- Melanoma \- Oropharyngeal squamous cell carcinoma \- Sarcoma MOLECULAR BASIS \- Caused by mutation in cyclin-dependent kinase inhibitor 2A (CDKN2A, 600160.0003 ) ▲ 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	MELANOMA-PANCREATIC CANCER SYNDROME	c0205747	29,868	omim	https://www.omim.org/entry/606719	2019-09-22T16:10:05	{"mesh": ["D004416"], "omim": ["606719"], "orphanet": ["404560"], "synonyms": ["Alternative titles", "FAMILIAL ATYPICAL MULTIPLE MOLE MELANOMA-PANCREATIC CARCINOMA SYNDROME"]}
A number sign (#) is used with this entry because tyrosinemia type III (TYRSN3) is caused by homozygous or compound heterozygous mutation in the HPD gene (609695), encoding 4-hydroxyphenylpyruvate dioxygenase, on chromosome 12q24. Heterozygous mutation in the HPD gene can cause hawkinsinuria (140350). Description Tyrosinemia type III is an autosomal recessive disorder caused by a deficiency in the activity of 4-hydroxyphenylpyruvate dioxygenase (HPD) and is characterized by elevated levels of blood tyrosine and massive excretion of its derivatives into urine. Patients with this disorder have mild mental retardation and/or convulsions, with the absence of liver damage (summary by Tomoeda et al., 2000). Clinical Features Giardini et al. (1983) described tyrosinemia without liver dysfunction due apparently to deficiency of 4-hydroxyphenylpyruvate dioxygenase (4HPPD). The patient, a 17-month-old girl, had acute intermittent ataxia and drowsiness. Her psychomotor development was normal. Protein restriction and vitamin C therapy failed to correct the biochemical abnormality. Liver biopsy was histologically normal. In liver biopsy tissue, obtained at 25 months of age, there was no detectable activity of 4HPPD, either in whole homogenate or cytosol fraction. Mixing experiments showed no inhibitor of either 4HPPD or tyrosine amino transferase (TAT). In the infant offspring of a sib-sib mating, Endo et al. (1983) demonstrated hypertyrosinemia without hepatic dysfunction, with normal soluble tyrosine aminotransferase and fumarylacetoacetase. The activity of 4-hydroxyphenylpyruvic acid oxidase (EC 1.13.11.27) in the patient's liver was about 5% of controls; the enzyme had a high Km for 4-hydroxyphenylpyruvic acid. The clinical picture was that of mild mental retardation. The mother had mild mental retardation and elevated blood tyrosine level (6.1 mg/dl as compared with 11.6 mg/dl in the infant). Cerone et al. (1997) reported the clinical and biochemical findings and the results of long-term follow-up in a new patient with this disorder presenting with severe mental retardation and neurologic abnormalities. They compared clinical phenotype with those reported in the 3 previously described patients. Ellaway et al. (2001) reviewed 9 previously reported patients with type III tyrosinemia and reported 4 additional patients. Five of the patients were detected by neonatal screening, 1 had some jitteriness on handling, and 1 had neonatal hepatitis; the others were clinically normal. One patient died accidentally at 105 days of age. Of the 12 patients surviving beyond infancy, the most common long-term complication was intellectual impairment in 9 patients. Three of 5 patients diagnosed by neonatal screening had psychomotor retardation but not all were treated in infancy. Neurologic abnormalities had been observed in 7 of the 8 patients diagnosed beyond the neonatal period. It was not clear whether a strict low tyrosine diet alters the natural history of tyrosinemia type III, although there remained suspicion that treatment may be important, at least in infancy. Molecular Genetics In 3 unrelated families with tyrosinemia type III, Ruetschi et al. (2000) identified 4 presumed pathogenic mutations (2 missense and 2 nonsense) in the HPD gene (609695.0001-609695.0004). Four individuals were homozygous and 1 was compound heterozygous. No correlation of the severity of the mutation and enzyme deficiency and mental function was found; furthermore, the recorded tyrosine levels did not correlate with the clinical phenotype. Animal Model Endo et al. (1990, 1991) described a mouse strain with hypertyrosinemia associated with absent 4-hydroxyphenylpyruvate dioxygenase activity in the liver. The mutant mouse had a CRM-negative mutation. The disorder was autosomal recessive. All the animals were apparently healthy with no evidence of hepatorenal dysfunction. Fumarylacetoacetase and tyrosine aminotransferases (both cytosolic and mitochondrial) were normal in the mutant mice. Endo et al. (1995) reported a single-nucleotide substitution in the Hpd gene as the cause of the phenotype. The mutation was predicted to result in a premature termination codon in exon 7 of the gene and partial skipping of the exon. History Bloxam et al. (1960) found that 14 of 1,276 infants tested had large amounts of p-hydroxyphenylpyruvic acid, p-hydroxyphenylactic acid, and tyrosine in the urine. The infants were on normal diet. A delay in maturation of an enzyme was postulated. A genetic basis was presumed. INHERITANCE \- Autosomal recessive ABDOMEN Liver \- Normal liver function NEUROLOGIC Central Nervous System \- Mental retardation, mild \- Seizures LABORATORY ABNORMALITIES \- 4-hydroxyphenylpyruvic acid dioxygenase deficiency (HPD) \- Tyrosinemia \- 4-hydroxyphenylpyruvic aciduria \- 4-hydroxyphenyllactic aciduria \- 4-hydroxyphenylacetic aciduria MISCELLANEOUS \- Allelic to Hawkinsinuria ( 140350 ) MOLECULAR BASIS \- Caused by mutation in the 4-hydroxyphenylpyruvate dioxygenase gene (HPD, 609695.0001 ) ▲ 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	TYROSINEMIA, TYPE III	c0268623	29,869	omim	https://www.omim.org/entry/276710	2019-09-22T16:21:28	{"doid": ["0050727"], "mesh": ["D020176"], "omim": ["276710"], "orphanet": ["69723"], "synonyms": ["Alternative titles", "4-HYDROXYPHENYLPYRUVIC ACID OXIDASE DEFICIENCY", "4-HYDROXYPHENYLPYRUVATE DIOXYGENASE DEFICIENCY"]}
Buerger disease is occasionally observed in brothers (Samuel, 1932; McKusick and Harris, 1961) or in father and son (McKusick, unpublished observations). It also has a high frequency in some ethnic groups, e.g., Japanese and Koreans (McKusick and Harris, 1961). De Moerloose et al. (1979) found a deficiency of HLA-B12 in patients with Buerger disease (2.2% vs 28% in controls). Adar et al. (1983) presented evidence for cellular sensitivity to collagen in Buerger disease. This disorder may, like other autoimmune diseases, have a genetic predisposition without a direct 'cause' by a mutant gene. Olin (2000) suggested that tobacco use plays a central role in the initiation and progression of Buerger disease. Diehm and Stammler (2001) suggested that in addition to tobacco use, hyperhomocysteinemia (see 603174) may be an important factor in Buerger disease. Limbs \- Coldness \- Raynaud's phenomenon \- Hyperhydrosis \- Pain Inheritance \- Autosomal recessive Skin \- Red, elevated areas over venous valves \- Digital ulcers ▲ 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	BUERGER DISEASE	c0040021	29,870	omim	https://www.omim.org/entry/211480	2019-09-22T16:30:18	{"doid": ["12918"], "mesh": ["D013919"], "omim": ["211480"], "icd-9": ["443.1"], "icd-10": ["I73.1"], "orphanet": ["36258"], "synonyms": ["Alternative titles", "THROMBOANGIITIS OBLITERANS"]}
A tumor of neurectodermal origin arising from ependymal cells that line the ventricles and central canal of the spinal cord, that can occur in both children and adults, and that is characterized by wide a range of clinical manifestations depending on the location of the tumor, such as intracranial hypertension for tumors originating in the posterior fossa, behavioural changes and pyramidal signs for supratentorial tumors, and dysesthesia for tumors of the spinal cord. They can be classified as myxopapillary ependymoma, subependymoma, ependymoma (low grade tumors) or anaplastic ependymoma (grade III tumors). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Ependymal tumor	c0014474	29,871	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=301	2021-01-23T18:47:13	{"mesh": ["D004806"], "omim": ["137800"], "umls": ["C0014474"], "icd-10": ["C71.7"]}
Congenital dyserythropoietic anemia type II (CDA II), or hereditary erythroblastic multinuclearity with positive acidified serum lysis test (HEMPAS)[1] is a rare genetic anemia in humans characterized by hereditary erythroblastic multinuclearity with positive acidified serum lysis test.[2] Congenital dyserythropoietic anemia type II Other namesHereditary erythroblastic multinuclearity with positive acidified serum lysis test (abbr HEMPAS) SpecialtyHematology ## Contents * 1 Genetics * 2 Diagnosis * 3 Treatment * 4 See also * 5 References * 6 Further reading * 7 External links ## Genetics[edit] CDA type II is caused by mutations in the SEC23B gene. This gene provides instructions for making a protein that is involved in the transport of other proteins within cells. During the development of red blood cells, this protein may help ensure that proteins are transported to the areas where they are needed. Researchers are working to determine how mutations in the SEC23B gene lead to the signs and symptoms of CDA type II.[3] Analyses of CDA II erythrocyte membranes showed that the band 3 glycoprotein is underglycosylated. An aberrant glycosylation pattern is seen in the polylactosamine carbohydrates which are normally attached to the band 3 and band 4.5 glycoproteins. The polylactosamines are, however, accumulated in the form of glycolipids. Therefore a genetic factor in CDA II appears to block the glycosylation of protein acceptors and shift these carbohydrates to the lipid acceptors. Structural analysis of CDA II band 3 carbohydrates identified truncated hybrid-type oligosaccharides and suggests that the Golgi glycosylation enzyme(s), alpha-mannosidase II or N-acetylglycosaminyltransferase II is defective in CDA II.[2] Type OMIM Gene Locus CDAN2 224100 SEC23B 20q11.2 ## Diagnosis[edit] The anemia associated with CDA type II can range from mild to severe, and most affected individuals have jaundice, hepatosplenomegaly, and the formation of hard deposits in the gallbladder called bilirubin gallstones. This form of the disorder is usually diagnosed in adolescence or early adulthood. An abnormal buildup of iron typically occurs after age 20, leading to complications including heart disease, diabetes, and cirrhosis.[3] ## Treatment[edit] Treatment consists of frequent blood transfusions and chelation therapy. Potential cures include bone marrow transplantation and gene therapy. ## See also[edit] * Congenital dyserythropoietic anemia * Thalassemia * Hemoglobinopathy * List of hematologic conditions ## References[edit] 1. ^ Fukuda MN (1999). "HEMPAS. Hereditary erythroblastic multinuclearity with positive acidified serum lysis test". Biochim Biophys Acta. 1455 (2–3): 231–9. doi:10.1016/S0925-4439(99)00070-8. PMID 10571015. 2. ^ a b Fukuda, Michiko N. (1993). "Congenital dyserythropoietic anaemia type II (HEMPAS) and its molecular basis". Baillière's Clinical Haematology. 6 (2): 493–511. doi:10.1016/S0950-3536(05)80156-8. PMID 8043936. 3. ^ a b "CDA - Genetics Home Reference". Ghr.nlm.nih.gov. 2012-07-02. Retrieved 2012-07-09. ## Further reading[edit] * McCann, Shaun R; Firth, R; Murray, Nuala; Temperley, I J (1980). "Congenital dyserythropoietic anaemia type II (HEMPAS): A family study". Journal of Clinical Pathology. 33 (12): 1197–201. doi:10.1136/jcp.33.12.1197. PMC 1146375. PMID 7451666. * Heimpel, Hermann; Anselstetter, Volker; Chrobak, Ladislav; Denecke, Jonas; Einsiedler, Beate; Gallmeier, Kerstin; Griesshammer, Antje; Marquardt, Thorsten; et al. (2003). "Congenital dyserythropoietic anemia type II: Epidemiology, clinical appearance, and prognosis based on long-term observation" (PDF). Blood. 102 (13): 4576–81. doi:10.1182/blood-2003-02-0613. PMID 12933587. * Congenital dyserythropoietic anemia at the US National Institutes of Health Home Genetic Reference ## External links[edit] Classification D * ICD-10: D64.4 * ICD-9-CM: 285.8 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and 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 dyserythropoietic anemia type II	c1306589	29,872	wikipedia	https://en.wikipedia.org/wiki/Congenital_dyserythropoietic_anemia_type_II	2021-01-18T18:41:26	{"mesh": ["D000742"], "icd-9": ["285.8"], "icd-10": ["D64.4"], "orphanet": ["98873"], "wikidata": ["Q5160424"]}
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: "Coccyx fracture" – news · newspapers · books · scholar · JSTOR (August 2019) (Learn how and when to remove this template message) Coccyx fracture Lateral radiograph showing a fracture of the coccyx, as well as a lower lumbar fracture SpecialtyOrthopedic A coccyx fracture is a fracture of the coccyx, commonly called a 'broken tailbone' or ‘puzzle fracture.’ The coccyx is located at the base of the spine, under the sacrum. It is the last section of the ape vertebral column. Most commonly in humans it comprises 3 to 5 fused (or, more rarely, separate) vertebrae, and is approximately 4 to 10 cm in length. The coccyx is attached to the sacrum by a fibrocartilaginous joint, called the sacrococcygeal symphysis, allowing for some (but little) movement. Anatomical diagram of a healthy coccyx ## Contents * 1 Causes * 2 Risk factors * 3 Diagnosis * 4 Treatment * 4.1 Surgery * 5 References ## Causes[edit] Causes of coccyx fracture can vary greatly, but are most commonly confined to falls into the seated position, or childbirth. ## Risk factors[edit] The following risk factors have been identified for coccyx fracture: * Lack of/reduced muscle mass * Advanced age * Osteoporosis * Being of the female sex (due to the wider pelvis typically found in females) * Violence Symptoms of coccyx fracture include: * Pain that increases in severity when sitting or getting up from a chair, or when experiencing bowel movement * Provoked pain over the tailbone * Nausea * Bruising or swelling in the tailbone area ## Diagnosis[edit] The standard workup of a suspected coccyx fracture includes medical history and a physical examination including a rectal examination.[1] X-ray has no quantifiable clinical impact,[2] and is regarded as a waste of resources and unnecessary exposure to ionizing radiation.[3] ## Treatment[edit] If the coccyx fracture is severe enough, short-term hospitalisation may be required, although this is extremely rare. More often, self-care at home is administered. Sitting on soft surfaces is recommended, as this reduces pressure on the coccyx. A 'donut' or 'wedge' cushion may be purchased – these are simply cushions with a hole in them to ensure that no weight is placed in the injured tailbone. Painkillers such as ibuprofen are also recommended, as is a diet high in fibre to soften stools and avoid constipation. Doctors will not usually attempt to correct a bad alignment, as muscles in the area are powerful and can pull the bone back into the 'bad' position. The bone is also very difficult to immobilise simply due to the sheer number of muscles attached to it, as well as the position. ### Surgery[edit] Following a coccyx fracture, surgery is not usually required. However, if the pain continues even after the fracture has healed, and is severe enough to cause serious disability, surgical removal of the coccyx (coccygectomy) may be required. ## References[edit] 1. ^ "coccyx (fracture)". GPnotebook. Retrieved 2019-07-02. 2. ^ Hanna, Tarek N.; Sadiq, Mahniya; Ditkofsky, Noah; Benayoun, Marc; Datir, Abhijit; Rohatgi, Saurabh; Khosa, Faisal (2016). "Sacrum and Coccyx Radiographs Have Limited Clinical Impact in the Emergency Department". American Journal of Roentgenology. 206 (4): 681–686. doi:10.2214/AJR.15.15095. ISSN 0361-803X. 3. ^ Henry Knipe. "Coccygeal fracture". Radiopaedia. Retrieved 2019-07-02. * v * t * e Fractures and cartilage damage General * Avulsion fracture * Chalkstick fracture * Greenstick fracture * Open fracture * Pathologic fracture * Spiral fracture Head * Basilar skull fracture * Blowout fracture * Mandibular fracture * Nasal fracture * Le Fort fracture of skull * Zygomaticomaxillary complex fracture * Zygoma fracture Spinal fracture * Cervical fracture * Jefferson fracture * Hangman's fracture * Flexion teardrop fracture * Clay-shoveler fracture * Burst fracture * Compression fracture * Chance fracture * Holdsworth fracture Ribs * Rib fracture * Sternal fracture Shoulder fracture * Clavicle * Scapular Arm fracture Humerus fracture: * Proximal * Supracondylar * Holstein–Lewis fracture Forearm fracture: * Ulna fracture * Monteggia fracture * Hume fracture * Radius fracture/Distal radius * Galeazzi * Colles' * Smith's * Barton's * Essex-Lopresti fracture Hand fracture * Scaphoid * Rolando * Bennett's * Boxer's * Busch's Pelvic fracture * Duverney fracture * Pipkin fracture Leg Tibia fracture: * Bumper fracture * Segond fracture * Gosselin fracture * Toddler's fracture * Pilon fracture * Plafond fracture * Tillaux fracture Fibular fracture: * Maisonneuve fracture * Le Fort fracture of ankle * Bosworth fracture Combined tibia and fibula fracture: * Trimalleolar fracture * Bimalleolar fracture * Pott's fracture Crus fracture: * Patella fracture Femoral fracture: * Hip fracture Foot fracture * Lisfranc * Jones * March * Calcaneal [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Coccyx fracture	c0149860	29,873	wikipedia	https://en.wikipedia.org/wiki/Coccyx_fracture	2021-01-18T19:08:47	{"umls": ["C0149860"], "wikidata": ["Q5139271"]}
Infantile cortical hyperostosis Other namesCaffey disease SpecialtyRheumatology Infantile cortical hyperostosis is a self-limited inflammatory disorder of infants that causes bone changes, soft tissue swelling and irritability. The disease may be present at birth or occur shortly thereafter. The cause is unknown. Both familial and sporadic forms occur. It is also known as Caffey disease or Caffey's disease. ## Contents * 1 Presentation * 2 Genetics * 3 Pathophysiology * 4 Diagnosis * 4.1 Differential diagnosis * 5 Prognosis * 6 Epidemiology * 7 History * 8 References * 9 External links ## Presentation[edit] An affected infant typically has the following triad of signs and symptoms: soft-tissue swelling, bone lesions, and irritability. The swelling occurs suddenly, is deep, firm, and may be tender. Lesions are often asymmetric and may affect several parts of the body. Affected bones have included the mandible, tibia, ulna, clavicle, scapula, ribs, humerus, femur, fibula, skull, ilium, and metatarsals. When the mandible (lower jaw bone) is affected, infants may refuse to eat, leading to failure to thrive.[citation needed] ## Genetics[edit] It has been associated with COL1A1.[1] ## Pathophysiology[edit] In the early stages of infantile cortical hyperostosis, biopsy shows inflammation of the periosteum and adjacent soft tissues. After this resolves, the periosteum remains thickened, and subperiosteal immature lamellar bone can be seen on biopsy, while the bone marrow spaces contain vascular fibrous tissue. Eventually, the inflammation and subperiosteal changes resolve, and hyperplasia of lamellar cortical bone can be seen.[citation needed] Radiographs initially show layers of periosteal new bone formation with cortical thickening. Periosteal new bone may cover the diaphysis of the bone, causing an increase in diameter of the bone. Over time, the periosteal new bone density increases, becoming homogenous with the underlying cortex. Eventually, the bone remodels and resumes a normal appearance.[citation needed] ## Diagnosis[edit] Anteroposterior radiograph of the skull showed massive sclerosis of the skull bone associated with significant cortical hyperostosis and enlargement of the mandible secondary to cortical new bone formation. Most infants with infantile cortical hyperostosis are diagnosed by physical examination. X-rays can confirm the presence of bone changes and soft tissue swelling. Biopsy of the affected areas can confirm the presence of typical histopathological changes. No specific blood tests exist, but tests such as erythrocyte sedimentation rate (ESR) and alkaline phosphatase levels are often elevated. A complete blood count may show anemia (low red blood cell count) and leukocytosis (high white blood cell count). Other tests may be done to help exclude other diagnoses. Ultrasound imaging can help diagnose prenatal cases.[citation needed] ### Differential diagnosis[edit] Osteomyelitis (bone infection), which is much more common than infantile cortical hyperostosis, must be excluded, since it requires urgent treatment. Other diagnoses that can mimic this disorder and need to be excluded include physical trauma, child abuse, Vitamin A excess, hyperphosphatemia, prostaglandin E1 and E2 administration, scurvy, infections (including syphilis), Ewing sarcoma, and metastatic neuroblastoma.[citation needed] ## Prognosis[edit] Infantile cortical hyperostosis is a self-limited condition, meaning that the disease resolves on its own without treatment, usually within 6–9 months. Long-term deformities of the involved bones, including bony fusions and limb-length inequalities, are possible but rare.[citation needed] ## Epidemiology[edit] The disease has been reported to affect 3 per 1000 infants younger than 6 months in the United States. No predilection by race or sex has been established. Almost all cases occur by the age of 5 months. The familial form is inherited in an autosomal dominant fashion with variable penetrance. The familial form tends to have an earlier onset and is present at birth in 24% of cases, with an average age at onset of 6.8 weeks. The average age at onset for the sporadic form is 9–11 weeks.[citation needed] Cortical hyperostosis is a potential side effect of long-term use of prostaglandins in neonates.[2] ## History[edit] Dr. John Caffey (1895–1978) first described infantile cortical hyperostosis in 1945. He described a group of infants with tender swelling in the soft tissues and cortical thickenings in the skeleton, with onset of these findings during the first 3 months of life. Dr. Caffey was regarded throughout the world as the father of pediatric radiology. His classic textbook, Pediatric X-Ray Diagnosis, which was first published in 1945, has become the recognized bible and authority in its field.[3] ## References[edit] 1. ^ Kamoun-Goldrat A, Martinovic J, Saada J, et al. (July 2008). "Prenatal cortical hyperostosis with COL1A1 gene mutation". Am. J. Med. Genet. A. 146A (14): 1820–4. doi:10.1002/ajmg.a.32351. PMID 18553566. S2CID 205309510. 2. ^ Lewis AB, Freed MD, Heymann MA, Roehl SL, Kensey RC (1981). "Side effects of therapy with prostaglandin E1 in infants with critical congenital heart disease". Circulation. 64 (5): 893–898. doi:10.1161/01.cir.64.5.893. PMID 7285304.CS1 maint: multiple names: authors list (link) 3. ^ Caffey J (November 1946). "Infantile cortical hyperostoses". J. Pediatr. 29 (5): 541–59. doi:10.1016/S0022-3476(46)80122-7. PMID 21002859. * Herring J (ed.). "Infantile Cortical Hyperostosis". Tachdjian's Pediatric Orthopaedics. Philadelphia PA: WB Saunders. pp. 1561–5. ## External links[edit] * Radiographs of Infantile Cortical Hyperostosis Classification D * ICD-10: M89.8 * ICD-9-CM: 756.59 * OMIM: 114000 * MeSH: D006958 * DiseasesDB: 29307 External resources * eMedicine: orthoped/151 article/406697 * GeneReviews: Caffey Disease * Orphanet: 1310 * v * t * e Bone and joint disease Bone Inflammation endocrine: * Osteitis fibrosa cystica * Brown tumor infection: * Osteomyelitis * Sequestrum * Involucrum * Sesamoiditis * Brodie abscess * Periostitis * Vertebral osteomyelitis Metabolic * Bone density * Osteoporosis * Juvenile * Osteopenia * Osteomalacia * Paget's disease of bone * Hypophosphatasia Bone resorption * Osteolysis * Hajdu–Cheney syndrome * Ainhum * Gorham's disease Other * Ischaemia * Avascular necrosis * Osteonecrosis of the jaw * Complex regional pain syndrome * Hypertrophic pulmonary osteoarthropathy * Nonossifying fibroma * Pseudarthrosis * Stress fracture * Fibrous dysplasia * Monostotic * Polyostotic * Skeletal fluorosis * bone cyst * Aneurysmal bone cyst * Hyperostosis * Infantile cortical hyperostosis * Osteosclerosis * Melorheostosis * Pycnodysostosis Joint Chondritis * Relapsing polychondritis Other * Tietze's syndrome Combined Osteochondritis * Osteochondritis dissecans Child leg: * hip * Legg–Calvé–Perthes syndrome * tibia * Osgood–Schlatter disease * Blount's disease * foot * Köhler disease * Sever's disease spine * * Scheuermann's_disease arm: * wrist * Kienböck's disease * elbow * Panner disease * v * t * e Diseases of collagen, laminin and other scleroproteins Collagen disease COL1: * Osteogenesis imperfecta * Ehlers–Danlos syndrome, types 1, 2, 7 COL2: * Hypochondrogenesis * Achondrogenesis type 2 * Stickler syndrome * Marshall syndrome * Spondyloepiphyseal dysplasia congenita * Spondyloepimetaphyseal dysplasia, Strudwick type * Kniest dysplasia (see also C2/11) COL3: * Ehlers–Danlos syndrome, types 3 & 4 * Sack–Barabas syndrome COL4: * Alport syndrome COL5: * Ehlers–Danlos syndrome, types 1 & 2 COL6: * Bethlem myopathy * Ullrich congenital muscular dystrophy COL7: * Epidermolysis bullosa dystrophica * Recessive dystrophic epidermolysis bullosa * Bart syndrome * Transient bullous dermolysis of the newborn COL8: * Fuchs' dystrophy 1 COL9: * Multiple epiphyseal dysplasia 2, 3, 6 COL10: * Schmid metaphyseal chondrodysplasia COL11: * Weissenbacher–Zweymüller syndrome * Otospondylomegaepiphyseal dysplasia (see also C2/11) COL17: * Bullous pemphigoid COL18: * Knobloch syndrome Laminin * Junctional epidermolysis bullosa * Laryngoonychocutaneous syndrome Other * Congenital stromal corneal dystrophy * Raine syndrome * Urbach–Wiethe disease * TECTA * DFNA8/12, DFNB21 see also fibrous proteins [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Infantile cortical hyperostosis	c1861980	29,874	wikipedia	https://en.wikipedia.org/wiki/Infantile_cortical_hyperostosis	2021-01-18T18:42:23	{"gard": ["2832", "1051"], "mesh": ["C566184", "D006958"], "umls": ["C1861980"], "icd-9": ["756.59"], "orphanet": ["1310"], "wikidata": ["Q3801522"]}
A number sign (#) is used with this entry because of evidence that susceptibility to Wilms tumor can be caused by mutation in the REST (600571) gene on 4q12. For a general phenotypic description and discussion of genetic heterogeneity of Wilms tumor, see WT1 (194070). Molecular Genetics To identify predisposition genes for Wilms tumor, Mahamdallie et al. (2015) performed exome sequencing in 24 individuals with Wilms tumor from 12 families and identified 2 different frameshift mutations (600571.0001, 600571.0002) that segregated with the disease in 2 unrelated families. Neither was present in the ICR1000 and ExAC browsers. The mutations were confirmed by Sanger sequencing. Subsequently, Mahamdallie et al. (2015) performed Sanger sequencing of the full coding sequence and intron-exon boundaries of the REST gene in 38 individuals with familial Wilms tumor from 27 families. They identified 2 missense mutations (e.g., H322R, 600571.0003) that were plausibly pathogenic on the basis of segregation with disease, absence from the ICR1000 and ExAC browsers, and predicted effect on REST function. Finally, Mahamdallie et al. (2015) sequenced 519 individuals with Wilms tumor and no family history of the disease. They identified 9 additional REST mutations that were considered pathogenic: 6 truncating mutations and 3 nonsynonymous mutations mapping to the DNA binding domain. Two of the mutations had been identified in familial Wilms tumor pedigrees, but there was no known relationship between these independently ascertained families. All tested variants showed abrogation of REST function. In 4 cases for whom parental DNA was available, 1 mutation had occurred de novo and 3 had been inherited, confirming incomplete penetrance. In summary, Mahamdallie et al. (2015) identified REST mutations in 16 individuals from 4 families and 9 nonfamilial Wilms tumor pedigrees. Ten of the 11 different mutations, including all of the nonsynonymous mutations, clustered in the DNA binding domain of REST. None was present in ICR1000 exome series of 993 or in the 61,312 individuals in the ExAC browser. Mahamdallie et al. (2015) concluded that their data established REST as a Wilms tumor predisposition gene accounting for approximately 2% of Wilms tumors, and recommended screening of REST in all familial cases. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	WILMS TUMOR 6	c0027708	29,875	omim	https://www.omim.org/entry/616806	2019-09-22T15:47:51	{"mesh": ["D009396"], "omim": ["616806"], "orphanet": ["654"], "synonyms": ["Alternative titles", "WILMS TUMOR, SUSCEPTIBILITY TO"]}
A rare pyruvate metabolism disorder characterized by neonatal onset of a mitochondrial encephalopathy with global developmental delay and the biochemical characteristics of lactic acidosis and increased serum pyruvate with normal lactate/pyruvate ratio. Additional reported manifestations include epilepsy, peripheral neuropathy, hypotonia, nystagmus, extensor plantar responses, hepatomegaly, and craniofacial dysmorphism (such as progressive microcephaly, epicanthus, long philtrum, and thin upper lip). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Mitochondrial pyruvate carrier deficiency	c3553607	29,876	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=447784	2021-01-23T16:52:41	{"omim": ["614741"], "icd-10": ["E74.4"]}
A number sign (#) is used with this entry because of evidence that Klippel-Feil syndrome-2 (KFS2) is caused by homozygous mutation in the MEOX1 gene (600147) on chromosome 17q21. Description Klippel-Feil syndrome (KFS) is a congenital anomaly characterized by a defect in the formation or segmentation of the cervical vertebrae, resulting in a fused appearance. The clinical triad consists of short neck, low posterior hairline, and limited neck movement, although less than 50% of patients demonstrate all 3 clinical features (Tracy et al., 2004). Clarke et al. (1998) proposed a classification system for KFS in which an autosomal recessive form is characterized by the most rostral fusion at C1 and the presence of severe associated anomalies, including short neck, cardiac defects, and craniofacial anomalies. For a general description and a discussion of genetic heterogeneity of Klippel-Feil syndrome, see KFS1 (118100). Clinical Features Lubs et al. (1963) reported a family in which 2 of 11 sibs had fusion of vertebrae C5-6; a third sib had narrowing of the interspace. The parents were probably consanguineous. Juberg and Gershanik (1976) reported a patient with KFS born of consanguineous parents. She had short neck, restricted cervical movement, and low posterior hairline. Radiographic examination showed C1 anomalies and fusion of C2-3 and C3-4. She also had hearing loss. Chemke et al. (1980) described absent ulna and ulnar ray bilaterally in a female infant with KFS. The parents, Iraqi Jews, were not known to be consanguineous. Congenital absence of the ulna is rare; it may occur with the Cornelia de Lange syndrome (122470). In a large kindred, da-Silva (1982) reported 4 sibships with a total of 7 females and 5 males with Klippel-Feil syndrome. Each had unaffected, first-cousin parents. The degree of vertebral fusion was variable: 6 patients had massive fusion of several cervical vertebrae and 2 had cervical, upper thoracic, and lumbar fusions. Fragoso et al. (1982) described an 8-year-old girl who, in addition to KFS, had frontonasal dysplasia, Sprengel deformity (184400), widely spaced nipples, and postaxial polydactyly of the left foot. Facial features included flat facies, low anterior and posterior hairlines, hypertelorism, high-arched palate, and low-set ears. She had a short neck with limited movements. Clarke et al. (1998) reported a family in which the proband displayed the classic KFS triad of vertebral fusion, very short neck, and low hairline associated with fusion of C1-4 and C5-7. Fusion of spinous processes C1-4 was present at birth and did not progress in the following year to include the vertebral bodies. Other features included cleft palate, large pointed ears, and cardiac ventriculoseptal defect. The maternal grandmother had cleft lip and palate without vertebral fusion and a maternal uncle was reported to have had a very short neck. The authors suggested autosomal recessive inheritance with variable expression. Erol et al. (2004) reported a 7-year-old girl of Turkish origin with Klippel-Feil syndrome and Poland anomaly (173800). She had the typical triad of KFS, including very short neck, low occipital hairline, and reduced bilateral neck movements. Radiographic examination showed fusion of C1 and C2 vertebrae. She also had absence of the right pectoralis muscle, hypoplastic right breast, hypoplastic costochondral junctions, and hypoplastic sternum consistent with Poland anomaly. She had no cardiac, vascular, or renal anomalies. Erol et al. (2004) noted that a child with features of KFS, Poland anomaly, and Moebius syndrome (157900) had been reported by Issaivanan et al. (2002), who postulated a disruption in the subclavian artery supply. Bayrakli et al. (2013) studied a consanguineous Turkish family in which 7 members had Klippel-Feil syndrome. All 7 had short neck, low posterior hairline, limited neck movements, and elevated scapula. Computerized tomography revealed anomalies of the foramen magnum, occipitalization of the atlas (C1 vertebrae), fusion of the atlas and axis (C2 vertebrae), fusion of some cervical vertebrae, and omovertebral bone causing Sprengel deformity. Magnetic resonance imaging showed scoliosis. Inheritance The occurrence of KFS in sibs and in consanguineous families suggests autosomal recessive inheritance of a form of the disorder (Juberg and Gershanik, 1976; da-Silva, 1982). Cytogenetics Ohashi et al. (1992) described a 6-year-old girl with Klippel-Feil-like phenotype associated with a de novo balanced translocation between chromosomes 5q and 17q with breakpoints at q11.2 and q23, respectively. She had midfacial hypoplasia with a low nasal root, a short nasal septum, a long philtrum, a thin upper lip, micrognathia, a low posterior hairline, a short and broad neck, brachydactyly, hypoplastic nails, and pes planus. Radiologic examination demonstrated fusion of C5-7. Psychosomatic development was normal. Ohashi et al. (1992) suggested that one of the genes responsible for the disorder was located at 5q11.2 or 17q23. Mapping Mohamed et al. (2013) studied a large consanguineous Saudi family with Klippel-Feil syndrome in which the proband was a 10-year-old girl exhibiting the clinical triad of the disorder, with a short neck, low posterior hairline, and inability to flex, extend, or rotate her neck or lift her right hand to touch the back of her neck; full skeletal survey confirmed the C2-C3 fusion and Sprengel deformity but no other skeletal defects. Autozygosity mapping identified only 1 run of homozygosity, on chromosome 17 (chr17:29,323,850-45,448,560; NCBI36), that was exclusively shared by the affected members of the family; it was subsequently confirmed by linkage analysis. By linkage analysis in a consanguineous Turkish family segregating Klippel-Feil syndrome, Bayrakli et al. (2013) found linkage to chromosome 17q12-q23 with a maximum lod score of 4.2. Molecular Genetics In a large consanguineous Saudi family segregating autosomal recessive Klippel-Feil syndrome mapping to chromosome 17q21.31, Mohamed et al. (2013) analyzed the candidate gene MEOX1 and identified a homozygous 1-bp deletion (600147.0001) that segregated fully with the disease and was not found in 210 Saudi controls. Sequencing of the MEOX1 gene in affected sibs from an unrelated consanguineous family revealed homozygosity for a nonsense mutation (600147.0002). In a consanguineous Turkish family segregating Klippel-Feil syndrome mapping to chromosome 17q12-q23, Bayrakli et al. (2013) identified a homozygous truncating mutation (Q84X; 600147.0003) in the MEOX1 gene. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Hearing loss, sensorineural (in one family) \- Hearing loss, conductive (in one family) \- Abnormally shaped ears (in one family) Mouth \- Cleft lip (in one family) \- Cleft palate (in one family) Neck \- Short neck \- Limited neck range of motion CARDIOVASCULAR Heart \- Ventriculoseptal defect (in one family) CHEST Ribs Sternum Clavicles & Scapulae \- Elevated scapulae \- Omovertebral bone \- Sprengel anomaly ( 184400 ) SKELETAL Skull \- Anomalies of the foramen magnum Spine \- Fusion of cervical vertebrae \- Scoliosis SKIN, NAILS, & HAIR Hair \- Low posterior hairline MISCELLANEOUS \- Based on reports of one consanguineous Saudi family and one consanguineous Turkish family (last curated December 2014) MOLECULAR BASIS \- Caused by mutation in the mesenchyme homeobox 1 gene (MEOX1, 600147.0001 ) ▲ 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	KLIPPEL-FEIL SYNDROME 2, AUTOSOMAL RECESSIVE	c0022738	29,877	omim	https://www.omim.org/entry/214300	2019-09-22T16:29:47	{"doid": ["10426"], "mesh": ["D007714"], "omim": ["214300"], "orphanet": ["2345"], "synonyms": ["Alternative titles", "KFS, AUTOSOMAL RECESSIVE", "CERVICAL VERTEBRAL FUSION, AUTOSOMAL RECESSIVE"]}
## Clinical Features Vietor et al. (1977) described an infant brother and sister with a 'new' storage disease characterized by cardiomegaly, generalized muscular hypotonia, cerebral dysfunction, and death at ages 10 and 17 months. Manifestations were attributed to lysosomal storage of a substance with a positive reaction with PAS and Best's stain and resistance to diastase. An increased renal excretion of ethanolamine, greatly increased hepatic ethanolamine, and diminished hepatic ethanolamine kinase were demonstrated. Ethanolamine is essential for the synthesis of phospholipids. Both parents showed increased renal excretion of taurine. The clinical picture resembled that of type II glycogenosis (232300). Neuro \- Cerebral dysfunction Inheritance \- Autosomal recessive Misc \- Death in infancy Lab \- Lysosomal storage of PAS-positive, diastase-resistant substance \- Increased renal excretion of ethanolamine \- Increased hepatic ethanolamine \- Decreased hepatic ethanolamine kinase Cardiac \- Cardiomegaly Muscle \- Generalized muscular hypotonia ▲ 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	ETHANOLAMINOSIS	c0268423	29,878	omim	https://www.omim.org/entry/227150	2019-09-22T16:28:07	{"mesh": ["C562651"], "omim": ["227150"], "synonyms": ["Alternative titles", "ETHANOLAMINE KINASE DEFICIENCY"]}
A rare, congenital, fetal lower urinary tract obstruction (LUTO) anomaly characterized by an abnormal congenital obstructing membrane or leaflets that are located within the posterior urethra associated with significant obstruction of the male bladder restricting normal bladder emptying. ## Epidemiology It is the most common anomaly of LUTO with a prevalence estimated at 1/4,750-6,250 male births. Posterior urethral valves (PUV) occur exclusively in males. ## Clinical description PUV represents a spectrum of severity ranging from a disease fatal in infancy to a disease that is minimal and may not manifest until later in life. In the most severe cases, characterized by antenatal oligohydramnios or anhydramnios, the newborn may presents with severe pulmonary distress and features of Potter sequence including wide-set eyes, flattened nose, receding chin and large, low-set ears deficient in cartilage. In toddlers and older children PUV may present with urinary incontinence, poor growth, urinary tract infections, hypertension, lethargy and ultimately renal failure. ## Etiology The embryology of the urethra is not completely understood, particularly as it pertains to pathologic anomalies. Several different theories have been proposed in the development of PUV. It represents a spectrum of severity based on the timing and severity of obstruction. Congenital obstruction of the urinary tract at a critical time in organogenesis has a profound and lifelong effect on kidney, ureteral and bladder function. The inability of urine to pass out of the body of the fetus results in oligohydramnios which in turn may lead to pulmonary hypoplasia and the features of Potter sequence. ## Diagnostic methods Postnatal diagnosis is suggested on renal ultrasound with findings of dilated, thick-walled bladder and a dilated posterior urethra. Postnatal diagnosis is confirmed with voiding cystotourethrography and cystoscopy. ## Differential diagnosis Differential diagnoses include anterior urethral valves, congenital urethral stricture, urethral atresia and Prune Belly syndrome. The diagnosis is then confirmed by postnatal physical examination and postnatal renal ultrasonography along with voiding cystourethrography. ## Antenatal diagnosis Antenatal diagnosis is based on ultrasound, possibly aided by magnetic resonance imaging studies. PUV is characterized by variably enlarged thick-walled, non-emptying urinary bladder and a dilated posterior urethra. Counseling is dependent upon the ultrasound findings that also suggest possible associated renal dysplasia at the time of prenatal diagnosis. ## Genetic counseling The majority of cases occur sporadically; however, some rare cases observed in siblings indicate autosomal recessive or x-linked recessive inheritance. ## Management and treatment Antenatal treatment involves urinary decompression with a vesico-amniotic shunt. Postnatally, PUV is treated using primary valve ablation or creation of a vesicostomy. Further surgical intervention is dependent on the status of the bladder function as well as renal function. Immediately after birth, infants are placed on antibiotic prophylaxis and a means of draining their bladder is accomplished using suprapubic or transurethral catheter diversion. Pulmonary function is assessed and fluid and electrolyte management performed. ## Prognosis The prognosis of PUV is variable depending on the degree of severity of the LUTO. Patients may be susceptible to urinary incontinence, urinary tract infections and progressive renal damage. Approximately one third of patients born with PUV progress to end stage renal disease and all patients need periodic long-term urologic follow-up care. Without intervention, patients are at risk of renal failure and bladder dysfunction. Fertility may be compromised in patients who are uremic. * European Reference Network [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Posterior urethral valve	c0238506	29,879	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93110	2021-01-23T17:02:09	{"gard": ["7439"], "omim": ["618612"], "umls": ["C0238506", "C0542520"], "icd-10": ["Q64.2"], "synonyms": ["PUV"]}
Carpenter syndrome is a condition characterized by the premature fusion of certain skull bones (craniosynostosis), abnormalities of the fingers and toes, and other developmental problems. Craniosynostosis prevents the skull from growing normally, frequently giving the head a pointed appearance (acrocephaly). In severely affected individuals, the abnormal fusion of the skull bones results in a deformity called a cloverleaf skull. Craniosynostosis can cause differences between the two sides of the head and face (craniofacial asymmetry). Early fusion of the skull bones can affect the development of the brain and lead to increased pressure within the skull (intracranial pressure). Premature fusion of the skull bones can cause several characteristic facial features in people with Carpenter syndrome. Distinctive facial features may include a flat nasal bridge, outside corners of the eyes that point downward (down-slanting palpebral fissures), low-set and abnormally shaped ears, underdeveloped upper and lower jaws, and abnormal eye shape. Some affected individuals also have dental abnormalities including small primary (baby) teeth. Vision problems also frequently occur. Abnormalities of the fingers and toes include fusion of the skin between two or more fingers or toes (cutaneous syndactyly), unusually short fingers or toes (brachydactyly), or extra fingers or toes (polydactyly). In Carpenter syndrome, cutaneous syndactyly is most common between the third (middle) and fourth (ring) fingers, and polydactyly frequently occurs next to the big or second toe or the fifth (pinky) finger. People with Carpenter syndrome often have intellectual disability, which can range from mild to profound. However, some individuals with this condition have normal intelligence. The cause of intellectual disability is unknown, as the severity of craniosynostosis does not appear to be related to the severity of intellectual disability. Other features of Carpenter syndrome include obesity that begins in childhood, a soft out-pouching around the belly-button (umbilical hernia), hearing loss, and heart defects. Additional skeletal abnormalities such as deformed hips, a rounded upper back that also curves to the side (kyphoscoliosis), and knees that are angled inward (genu valgum) frequently occur. Nearly all affected males have genital abnormalities, most frequently undescended testes (cryptorchidism). A few people with Carpenter syndrome have organs or tissues within their chest and abdomen that are in mirror-image reversed positions. This abnormal placement may affect several internal organs (situs inversus); just the heart (dextrocardia), placing the heart on the right side of the body instead of on the left; or only the major (great) arteries of the heart, altering blood flow. The signs and symptoms of this disorder vary considerably, even within the same family. The life expectancy for individuals with Carpenter syndrome is shortened but extremely variable. The signs and symptoms of Carpenter syndrome are similar to another genetic condition called Greig cephalopolysyndactyly syndrome. The overlapping features, which include craniosynostosis, polydactyly, and heart abnormalities, can cause these two conditions to be misdiagnosed; genetic testing is often required for an accurate diagnosis. ## Frequency Carpenter syndrome is thought to be a rare condition; approximately 70 cases have been described in the scientific literature. ## Causes Mutations in the RAB23 or MEGF8 gene cause Carpenter syndrome. The RAB23 gene provides instructions for making a protein that is involved in a process called vesicle trafficking, which moves proteins and other molecules within cells in sac-like structures called vesicles. The Rab23 protein transports vesicles from the cell membrane to their proper location inside the cell. Vesicle trafficking is important for the transport of materials that are needed to trigger signaling during development. For example, the Rab23 protein regulates a developmental pathway called the hedgehog signaling pathway that is critical in cell growth (proliferation), cell specialization, and the normal shaping (patterning) of many parts of the body. The MEGF8 gene provides instructions for making a protein whose function is unclear. Based on its structure, the Megf8 protein may be involved in cell processes such as sticking cells together (cell adhesion) and helping proteins interact with each other. Researchers also suspect that the Megf8 protein plays a role in normal body patterning. Mutations in the RAB23 or MEGF8 gene lead to the production of proteins with little or no function. It is unclear how disruptions in protein function lead to the features of Carpenter syndrome, but it is likely that interference with normal body patterning plays a role. For reasons that are unknown, people with MEGF8 gene mutations are more likely to have dextrocardia and other organ positioning abnormalities and less severe craniosynostosis than individuals with RAB23 gene mutations. ### Learn more about the genes associated with Carpenter syndrome * MEGF8 * RAB23 ## 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	Carpenter syndrome	c4551510	29,880	medlineplus	https://medlineplus.gov/genetics/condition/carpenter-syndrome/	2021-01-27T08:25:09	{"gard": ["6003"], "omim": ["201000", "614976"], "synonyms": []}
A number sign (#) is used with this entry because of evidence that Woodhouse-Sakati syndrome (WDSKS) is caused by homozygous mutation in the C2ORF37 gene (DCAF17; 612515) on chromosome 2q31. Clinical Features Woodhouse and Sakati (1983) reported a total of 7 Saudi Arabian individuals from 2 consanguineous families with a combination of hypogonadism, partial alopecia, diabetes mellitus, mental retardation, and deafness. The first family had 2 affected males and 2 affected females ranging in age from 16 to 22 years. The second family had 1 affected male and 1 affected female aged 47 and 40 years, respectively. One female from each family initially presented with primary amenorrhea and failure of sexual development. All patients were subsequently found to have hypogonadism with low estradiol or testosterone levels. Luteinizing hormone (LHB; 152780) and follicle-stimulating hormone (FSH; 136530) were increased in 2 women (hypergonadotropic ovarian failure) and normal in all the other patients. Three males had hypothalamic hypogonadotrophic testicular failure, and the remaining female had both hypothalamic and ovarian failure. Examination of 1 woman showed hypoplastic uterus, rudimentary fallopian tubes, and streak ovaries. Testicular histology of 1 man showed hypospermatogenesis and prominent Sertoli cells. There was variable loss of eyebrow and scalp hair, the latter being short, sparse, and fine. Hair loss was most severe in the older patients. All patients were diabetic with inappropriately low serum insulin levels. All patients had some degree of mental retardation, ranging from mild to severe. Four patients tested had sensorineural hearing loss. Electrocardiogram (ECG) showed flattening of the T wave in all patients. Devriendt et al. (1996) reported a brother and sister with a progressive extrapyramidal movement disorder with onset in adolescence associated with progressive alopecia and primary hypogonadism. The parents were first cousins once removed. Of 9 children total, 2 were affected and 1 died immediately after birth with severe arthrogryposis. Progressive learning problems, speech difficulties, and gait disturbance were first observed at age 12 years in the brother. He had decreased muscle strength and hand control, resulting in difficulties in fine motor skills such as writing. He was trained vocationally as a plumber. At age 17 years, he was seen by an endocrinologist for delayed puberty with absence of pubic and facial hair growth and prepubertal testes and penis. Neurologic examination at age 17 showed dystonia of the left arm and dysarthria. Progressive alopecia was observed in the early 20s. At age 47, he was able to walk very little and could produce only a few vocal sounds and had difficulty eating and drinking. His uncontrolled movements were dystonic and choreoathetotic, especially in the upper limbs. The sister showed learning difficulties in primary school and she required special education. At age 14 she developed progressive gait disturbance and was wheelchair-bound by her early 20s. Around the age of 14, a slowly progressive dysarthria and alopecia developed. There was primary amenorrhea, with no development of secondary female sexual characteristics. Facial appearance was very similar to that of her brother. Gul et al. (2000) reported a 32-year-old Turkish man with mental retardation, partial alopecia, diabetes mellitus, hypogonadotrophic hypogonadism, deafness, and nervous system involvement. He had a eunuchoid appearance, flat occiput, triangular face, thin and sparse scalp hair (microscopic examination showed pili annulati), high forehead, frontal bossing, mild hypertelorism, and short and sparse eyebrows. Other features included downslanting palpebral fissures, a prominent nasal root, dental malocclusion, and a high-arched palate. Neurologic examination showed dysarthria, mild weakness in the distal muscles, sensory polyneuropathy, and equivocal Babinski sign. Other studies, such as central motor conduction time and brainstem auditory evoked responses, indicated involvement of both the central and peripheral nervous systems. A younger and older brother of the proband had diabetes mellitus and similar facial features, and the older brother died at age 30 of unknown cause. The parents were first cousins. Gul et al. (2000) referred to the disorder in the proband as 'Woodhouse and Sakati syndrome' and suggested autosomal recessive inheritance. Al-Semari and Bohlega (2007) reported 12 Saudi families with an autosomal recessive multisystem disorder reminiscent of that described by Devriendt et al. (1996). Ten of the families were consanguineous. One of the families had been previously reported by Woodhouse and Sakati (1983) and 3 affected members had since developed a neurologic extrapyramidal syndrome with choreoathetoid movements and dystonia. The proband was unable to stand or walk, had scoliosis, hyperreflexia, and extensor plantar responses. Brain MRI of the proband, 1 sister, and 1 cousin showed diffuse white matter disease. Characteristic features in affected members of the other families included partial alopecia, dystonia, hypogonadism with lack of secondary sexual characteristics, cognitive impairment, deafness, diabetes mellitus, and signal abnormalities on brain MRI. Pelvic examination in female members of affected families showed infantile uterus and/or small ovaries. ECG showed abnormal T waves in 4 patients. Laboratory studies showed that 7 patients had increased FSH and LH, 4 men had low testosterone, and 2 women had low estradiol. Eight patients had biochemical evidence of hypothyroidism. The most striking and consistent laboratory abnormality was low serum insulin growth factor-1 (IGF1; 147440) with normal growth hormone (GH; 139250). Al-Semari and Bohlega (2007) suggested that the disorder could be an undescribed type of neuro-endocrine-ectodermal syndrome. Medica et al. (2007) reported a 52-year-old woman of Croatian origin who had the phenotypic findings of Woodhouse-Sakati syndrome, including hypogonadism, sparse hair, diabetes mellitus, sensorineural hearing impairment, mild mental retardation, and flattened T waves on EKG. Koshy et al. (2008) reported 3 sibs from a consanguineous Indian family with Woodhouse-Sakati syndrome who showed phenotypic variability. The female proband presented with idiopathic thrombocytopenic purpura and had camptodactyly of the fourth and fifth fingers as did her affected brother. She and her affected sister had hypergonadotropic hypogonadism, whereas their brother had hypogonadotropic hypogonadism. A female cousin of the sibs was reported to have had alopecia and amenorrhea, and was pale and edematous when she died of severe diarrhea and dehydration at 32 years of age. Schneider and Bhatia (2008) described a brother and sister from a consanguineous Middle Eastern family with adult-onset dystonia associated with sensorineural deafness, seizures, sensory neuropathy, mental retardation, alopecia, hypogonadism, and diabetes mellitus. The authors stated that although these features were suggestive of Woodhouse-Sakati syndrome, they also considered a diagnosis of mitochondrial disease, but mitochondrial mutations and muscle biopsy were negative; other causes of secondary dystonia were also excluded. Steindl et al. (2010) studied 3 affected members of an Italian family with Woodhouse-Sakati syndrome who were found to have a homozygous nonsense mutation in the C2ORF37 gene (612515.0006) by Alazami et al. (2010) (see MOLECULAR GENETICS). The proband was a 58-year-old man who exhibited the full constellation of hypogonadism, alopecia, diabetes mellitus, cognitive impairment, and dystonia. His sister, who was reported to have died at 46 years of age of myocardial infarction and heart block, had autopsy findings that suggested the presence of alopecia and hypogonadism, with complete absence of the uterus. There was also a distant female relative in this pedigree who had similar clinical features to those of the proband; laparoscopy revealed absence of fallopian tubes, streak gonads, and hypoplastic uterus. She also had psychosis and hallucinations; Steindl et al. (2010) stated that psychiatric features should be added to the clinical spectrum of Woodhouse-Sakati syndrome. Examination of photographs at different ages demonstrated the appearance of progressive aging, a triangular face shape with prominent nasal root, and prominent ears with large ear lobes. There was progressive cognitive decline in these patients after normal development in childhood, culminating in severe cognitive impairment with little spontaneous speech in adulthood. In addition, anodontia presented from an early age in all 3 patients. Mapping Alazami et al. (2008) performed genomewide linkage analysis on 3 affected sibs from 1 of the original Saudi families described by Woodhouse and Sakati (1983) and identified an extended autozygous region encompassing chromosome 2q22.3-q35. Inclusion of another Saudi family with 4 affected sibs confirmed the homozygosity and yielded a maximum multipoint lod score of 6.13 from markers D2S2284 to D2S1791; fine mapping further narrowed the critical region to a 1.2-Mb interval containing 13 known and predicted genes and pseudogenes. Molecular Genetics In affected members of 2 Saudi families with Woodhouse-Sakati syndrome, including 1 of the original families described by Woodhouse and Sakati (1983), Alazami et al. (2008) identified homozygosity for a 1-bp deletion in the C2ORF37 gene (612515.0001); 6 additional Saudi families with the disorder were also found to be homozygous for the mutation. SNP-based haplotype analysis confirmed a founder effect, and the deletion likely arose approximately 55 generations earlier. Alazami et al. (2008) subsequently identified homozygosity of a different 1-bp deletion in the C2ORF37 gene (612515.0002) in the Eastern European patient previously reported by Medica et al. (2007), and respective homozygous splice site mutations (612515.0003-612515.0004) in the Indian family reported by Koshy et al. (2008) and the Middle Eastern family reported by Schneider and Bhatia (2008). The mutations segregated fully with disease in all families, and were not found in ethnically matched controls. Alazami et al. (2010) analyzed the C2ORF37 gene in 7 patients with Woodhouse-Sakati syndrome from 4 unrelated families, 2 of Italian origin, 1 of French-Gypsy origin, and 1 of Turkish origin, and identified homozygosity for 3 nonsense mutations (612515.0005-612515.0007) and 1 deletion/insertion mutation (612515.0008). Screening of the C2ORF37 gene in a cohort of 11 patients with deafness and dystonia but no hypogonadism, alopecia, or mental retardation did not reveal any mutations, suggesting that mutation in C2ORF37 does not contribute significantly to cases presenting with isolated elements of Woodhouse-Sakati syndrome. Alazami et al. (2010) found no correlation between clinical expressivity and site of mutation, and noted that the intrafamilial variability in the mutation-positive patients indicated that modifiers likely play an important role in this disease. INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Triangular facies (in some patients) Ears \- Deafness, sensorineural \- Prominent ears (in some patients) Nose \- Prominent nasal root (in some patients) Teeth \- Anodontia (in some patients) CARDIOVASCULAR Heart \- ECG shows flattened T waves GENITOURINARY \- Hypogonadism External Genitalia (Male) \- Small penis Internal Genitalia (Male) \- Small testes \- Testicular biopsy shows hypospermatogenesis \- Atrophic seminiferous tubules Internal Genitalia (Female) \- Primary ovarian failure \- Rudimentary fallopian tubes \- Hypoplastic uterus \- Streak ovaries SKIN, NAILS, & HAIR Hair \- Alopecia, partial, primarily involving scalp and eyebrows \- Short, sparse, fine hair \- Loss of eyebrow hair NEUROLOGIC Central Nervous System \- Progressive cognitive decline following normal development in childhood (in some patients) \- Mental retardation \- Dystonia \- Dysarthria \- Choreoathetosis \- Extrapyramidal symptoms \- Psychosis (rare) \- Hallucinations (rare) \- MRI shows white matter lesions \- MRI shows decreased signal intensities in the basal ganglia ENDOCRINE FEATURES \- Diabetes mellitus \- Hypergonadotropic hypogonadism \- Hypogonadotropic hypergonadism \- Failure of secondary sexual development LABORATORY ABNORMALITIES \- Decreased testosterone \- Decreased estradiol \- Hyperlipidemia \- Decreased serum insulin-like growth factor 1 (IGF1) \- Increased thyroid-stimulating hormone (TSH) \- Decreased thyroxine (T4) MISCELLANEOUS \- Variable phenotype \- Onset of mental impairment in early childhood \- Onset of other symptoms in adolescence or early adulthood \- Patients do not have clinical hypothyroidism MOLECULAR BASIS \- Caused by mutation in the DDB1- and CUL4-associated factor 17 gene (DCAF17, 612515.0001 ) ▲ 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	WOODHOUSE-SAKATI SYNDROME	c0342286	29,881	omim	https://www.omim.org/entry/241080	2019-09-22T16:26:37	{"mesh": ["C536742"], "omim": ["241080"], "orphanet": ["3464"], "synonyms": ["Alternative titles", "HYPOGONADISM, ALOPECIA, DIABETES MELLITUS, MENTAL RETARDATION, DEAFNESS, AND EXTRAPYRAMIDAL SYNDROME", "EXTRAPYRAMIDAL DISORDER, PROGRESSIVE, WITH PRIMARY HYPOGONADISM, MENTAL RETARDATION, AND ALOPECIA"], "genereviews": ["NBK378974"]}
A rare pediatric inflammatory rheumatic disease characterized by the presence of arthritis accompanied by either psoriasis or at least two of the following supporting features; presence of nail pitting, onycholysis, dactylitis, or a family history of psoriasis in a first degree relative. Patients are younger than 16 years of age and the disease lasts longer than 6 weeks. ## Epidemiology The incidence of juvenile idiopathic arthritis (JIA) in Caucasian is 8.3/100,000. Psoriatic juvenile idiopathic arthritis represents up to 10% of all JIA subtypes. Incidence and prevalence vary among populations, depending on race, immunogenetic susceptibility, and environmental influences. ## Clinical description Juvenile idiopathic arthritis is considered an autoimmune disease, which may arise from an abnormal immunologic response triggered by environmental factors such as infection or trauma in a genetically predisposed subject. The onset of arthritis precedes the psoriatic cutaneous manifestations in more than 60% of cases, sometimes several years earlier, and it usually presents in an asymmetric oligoarthritis pattern. Monoarthritis (inflammation at one joint at a time) is relatively common at the onset, with isolated involvement of knee and small joints of hands and feet. ## Etiology The etiology of psoriasis-related juvenile idiopathic arthritis is not currently known, although all juvenile idiopathic arthritis subtypes are most likely complex genetic traits as they lack single-gene, Mendelian patterns of inheritance. Inherited risk factors for both disease susceptibility and disease severity have been reported; the highly polymorphic HLA genes confer the strongest genetic effects. ## Diagnostic methods Diagnosis relies on observation of the clinical manifestations and ruling out other potential causes or illnesses. The disease is characterized either by the presence of a form of arthritis and psoriasis, or by the presence of arthritis associated with two or more of the following signs: dactylitis, nail pitting or onycholysis, or a family history of psoriasis in a first-degree relative. Exclusion criteria include the presence of systemic arthritis, HLA B27-positivity in males with onset of arthritis after 6 years of age, detection of rheumatoid Factor IgM in two test samples taken three months apart, the presence, or family history in a first degree relative, of ankylosing spondylarthritis, enthesitis and arthritis, sacroiliitis with an inflammatory bowel disease, or acute anterior uveitis. ## Differential diagnosis The differential diagnosis of arthritis associated with psoriasis is extensive. It includes other diseases associated with arthritis, including infectious, inflammatory and hemato-oncologic diseases. Specific examples include ankylosing spondylitis, reactive arthritis, inﬂamatory bowel disease, Behçet disease, Kawasaki disease, sarcoidosis, Blau syndrome, systemic lupus erythematosus, Sweet syndrome, and some infections such as Lyme or Whipple disease. ## Management and treatment Treatment of psoriasis-related JIA usually involves treatment with non-steroidal anti-inflammatory drugs (NSAIDs) and, when insufficient, disease modifying anti-rheumatic drugs (DMARDs; methotrexate) and then biological DMARDs (TNF inhibitor agents: etanercept or adalimumab). ## Prognosis Juvenile idiopathic arthritis has been considered (before the use of biological DMARDs) an important cause of short- and long-term acquired disability in children, impaired physical health, reduced quality of life and higher unemployment later on in life. Effective therapy helps avoid progression to the polyarticular form from the monarticular form. Furthermore, chronic uveitis may occur in 10 to 15% of children with psoriatic juvenile idiopathic arthritis. Therefore, early detection and intervention is extremely important. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Psoriasis-related juvenile idiopathic arthritis	c3714758	29,882	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=85436	2021-01-23T18:14:00	{"gard": ["10970"], "mesh": ["D001171"], "umls": ["C0409672"], "icd-10": ["L40.5+", "M09.0*"], "synonyms": ["Juvenile psoriatic arthritis", "Psoriasis-related JIA"]}
Congenital chronic diarrhea with protein-losing enteropathy is a rare, genetic, intestinal disease characterized by early-onset, chronic, non-infectious, non-bloody, watery diarrhea associated with protein-losing enteropathy which results in hypoalbuminemia, hypogammaglobulinemia and elevated stool alpha-1-antitrypsin. Patients typically present severe, intractable diarrhea, failure to thrive, recurrent infections and edema. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and 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 chronic diarrhea with protein-losing enteropathy	c4014516	29,883	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=329242	2021-01-23T17:09:19	{"omim": ["615863", "618183"], "icd-10": ["P78.3"], "synonyms": ["Congenital chronic diarrhea with exudative enteropathy"]}
A syndrome characterized by unilateral or bilateral coronal synostosis, facial asymmetry, ptosis, strabismus and small ears with prominent superior and/or inferior crus, among other less common manifestations. ## Epidemiology Saethre-Chotzen syndrome (SCS) prevalence ranges from 1/25,000 to 1/50,000 livebirths. ## Clinical description SCS has a variable spectrum of manifestations. Classic SCS presents at birth with synostosis of coronal (less commonly in conjunction with sagittal, metopic or lambdoid) sutures resulting in abnormal skull shape, facial asymmetry, low frontal hairline, ptosis, strabismus, tear duct stenosis and small ears with prominent crus. Brachydactyly, broad toes, partial cutaneous syndactyly of digits 2 and 3 of the hand, duplicated distal phalanx of the hallux are also often present. Intelligence is normal in most, but mild to severe developmental delay has been reported, primarily in cases with a large genomic deletion. Some may experience conductive and/or sensorineural hearing loss. Less common manifestations include short stature, hypertelorism, cleft palate, bifid uvula, maxillary hypoplasia, lacrimal duct stenosis, parietal foramina, vertebral anomalies, radioulnar synostosis, obstructive sleep apnea and congenital heart malformations. Mild phenotypes include patients with ptosis or blepharophimosis with or without craniosynostosis. Elevated intracranial pressure (ICP) associated with severe cases of synostosis may lead to headaches, visual loss, seizures and death if untreated. ## Etiology SCS is due to point mutations or deletions involving (or removing completely) the TWIST1 gene (7p21), which encodes a basic helix-loop-helix (bHLH) transcription factor responsible for cell lineage determination and differentiation. Loss of function mutations in this gene lead to the induction of premature cranial suture fusion. Gene deletions cause more severe phenotypes, usually associated with significant neurocognitive delays. ## Diagnostic methods Diagnosis is based mainly on the presence of characteristic clinical findings. CT of the head and radiographs are useful in characterizing abnormalities of the skull, spine and limbs. Molecular genetic testing can identify a TWIST1 mutation or deletion, confirming diagnosis. ## Differential diagnosis Although several features (such as 2-3 syndactyly of the hand) are unique to SCS, differential diagnoses include other syndromic forms of craniosynostosis such as Muenke, Baller-Gerold, Pfeiffer, and Crouzon syndromes as well as isolated unilateral coronal synostosis. Robinow_Sorauf syndrome is now considered within the spectrum of SCS, typically with milder features. Mutations in FGFR3, FGFR2, TCF12, RECQL4, and EFNB1 have been reported to cause synostosis conditions that phenotypically overlap with SCS. This is not surprising, as there is evidence that FGFR and TWIST1 may be integrated into overlapping pathways, including in osteoblast differentiation. In addition, TWIST1 mutations have been noted in some cases of isolated single-suture craniosynostosis, including sagittal and unicoronal cases. ## Antenatal diagnosis Prenatal testing for a TWIST1 mutation is rare, but it can be performed in families with a known mutation or when an ultrasound shows craniosynostosis of unknown etiology. ## Genetic counseling SCS is inherited as an autosomal dominant trait. Genetic counseling is valuable. Genetic counseling should be proposed to individuals having the disease-causing mutation informing them that there is 50% risk of passing the mutation to offspring. ## Management and treatment Treatment of SCS requires management by a multidisciplinary craniofacial team with follow-up until young adulthood. In general, patients must undergo cranioplasty in the first year of life to increase the intracranial volume and restore a more normal head shape. Recurrent increased ICP may necessitate further surgical expansion procedures. In childhood, orthodontic care and/or midfacial surgery may be necessary for treatment of airway obstruction and malocclusion. In those with cleft palate, surgical closure can be performed in the context of other malformations, with evaluation for velopharyngeal insufficiency and speech therapy offered as necessary. Routine evaluations of facial growth, hearing loss and psychomotor development are needed, as well as regular ophthalmologic examinations to monitor strabismus, amblyopia or chronic papilledema (that indicates increased ICP). Early intervention programs should be offered to children with developmental delay. Augmentation of hearing and supportive interventions related to deafness should be pursued when indicated. ## Prognosis In most cases, when treated and monitored from an early age, the prognosis is excellent. Developmental prognosis is worse for patients with a TWIST1 deletion, compared to those with point mutations. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Saethre-Chotzen syndrome	c0175699	29,884	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=794	2021-01-23T18:46:07	{"gard": ["7598"], "mesh": ["D000168"], "omim": ["101400", "180750"], "umls": ["C0175699"], "icd-10": ["Q87.0"], "synonyms": ["ACS3", "Acrocephalosyndactyly type 3", "SCS"]}
Solitary fibrous tumor Other namesFibrous tumor of the pleura Micrograph of a solitary fibrous tumor. H&E stain. SpecialtyOncology Solitary fibrous tumor (SFT), also known as fibrous tumor of the pleura, is a rare mesenchymal tumor originating in the pleura[1] or at virtually any site in the soft tissue including seminal vesicle.[2] Approximately 78% to 88% of SFT's are benign and 12% to 22% are malignant.[3] ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 3 Treatment * 4 Prognosis * 5 History * 6 See also * 7 Additional images * 8 References * 9 External links ## Signs and symptoms[edit] About 80% of pleural SFTs originate in the visceral pleura, while 20% arise from parietal pleura.[4] Although they are often very large tumors (up to 40 cm. in diameter), over half are asymptomatic at diagnosis.[4] While some researchers have proposed that a SFT occupying at least 40% of the affected hemithorax be considered a "giant solitary fibrous tumor",[5] no such "giant" variant has yet been recognized within the most widely used pleural tumor classification scheme.[1] Some SFTs are associated with the paraneoplastic Doege–Potter syndrome, which is caused by tumor production of IGF-2. ## Pathophysiology[edit] Recurrent somatic fusions of the two genes, NGFI-A–binding protein 2 (NAB2) and STAT6, located at chromosomal region 12q13, have been identified in solitary fibrous tumors. This PA chest radiograph demonstrates an abnormal contour in the right hilar region, with visualization of the pulmonary vessels through the mass (the hilar overlay sign) indicating its posterior mediastinal location. On resection this was found to be a benign solitary fibrous tumor of the pleura. This axial CT image with intravenous contrast (same patient as in the above chest radiograph) reveals what appears to be a posterior mediastinal mass, which was surgically removed and found to be a solitary fibrous tumor of the pleura. [citation needed] ## Treatment[edit] The treatment of choice for both benign and malignant SFT is complete en bloc surgical resection. ## Prognosis[edit] Prognosis in benign SFTs is excellent. About 8% will recur after first resection, with the recurrence usually cured after additional surgery.[3] The prognosis in malignant SFTs is much more guarded. Approximately 63% of patients will have a recurrence of their tumor, of which more than half will succumb to disease progression within 2 years.[3] Adjuvant chemotherapy and/or radiotherapy in malignant SFT remains controversial.[3] ## History[edit] SFT was first mentioned in the scientific literature by Wagner.[6] The first discussion of its clinical and pathological properties was by Klemperer and Rabin.[3][7] SFTs have also been known as hemangiopericytomas although this term has now been discontinued from WHO tumor classifications.[citation needed] Over the years pleural SFTs acquired a number of synonyms, including localized fibrous tumor, benign mesothelioma, localized fibrous mesothelioma, submesothelial fibroma, and pleural fibroma. The use of names that include ‘mesothelioma’ for this tumor is discouraged because of potential confusion with diffuse malignant mesothelioma, a much more serious disease.[1] ## See also[edit] * Hemangiopericytoma * Myopericytoma ## Additional images[edit] * Solitary fibrous tumor - low magnification. H&E stain. * Solitary fibrous tumor - high magnification. H&E stain. ## References[edit] 1. ^ a b c Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC (Eds.): World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart. IARC Press: Lyon 2004. 2. ^ Khandelwal, Ashish; Virmani, Vivek; Amin, Md. Shahrier; George, Uttam; Khandelwal, Kanika; Gorsi, Ujjwal (2013). "Radiology–pathology conference: malignant solitary fibrous tumor of the seminal vesicle". Clinical Imaging. 37 (2): 409–413. doi:10.1016/j.clinimag.2012.04.027. PMID 23466005. 3. ^ a b c d e Robinson LA. Solitary fibrous tumor of the pleura. Cancer Control 2006;13:264-9. 4. ^ a b Briselli M, Mark EJ, Dickersin GR. Solitary fibrous tumors of the pleura: eight new cases and review of 360 cases in the literature" Cancer 1981;47:2678-89. 5. ^ Pinedo-Onofre JA, Robles-Pérez E, Peña-Mirabal ES, Hernández-Carrillo JA, Téllez-Becerra JL. [Giant solitary fibrous tumor of the pleura.] Cir Cir 2010;78:31-43. [Article in Spanish]. 6. ^ Wagner E. Das tuberkelahnliche lymphadenom (der cytogene oder reticulirte tuberkel). Arch Heilk (Leipig). 1870;11:497.> 7. ^ de Perrot M, Fischer S, Brundler MA, et al. Solitary fibrous tumors of the pleura. Ann Thorac Surg. 2002;74:285-293. ## External links[edit] Classification D * ICD-O: M8815/0 * MeSH: D054364 * SNOMED CT: 128736003 External resources * Orphanet: 2126 * [1] World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart. (Download Page) * v * t * e Cancer involving the respiratory tract Upper RT Nasal cavity Esthesioneuroblastoma Nasopharynx Nasopharyngeal carcinoma Nasopharyngeal angiofibroma Larynx Laryngeal cancer Laryngeal papillomatosis Lower RT Trachea * Tracheal tumor Lung Non-small-cell lung carcinoma * Squamous-cell carcinoma * Adenocarcinoma (Mucinous cystadenocarcinoma) * Large-cell lung carcinoma * Rhabdoid carcinoma * Sarcomatoid carcinoma * Carcinoid * Salivary gland–like carcinoma * Adenosquamous carcinoma * Papillary adenocarcinoma * Giant-cell carcinoma Small-cell carcinoma * Combined small-cell carcinoma Non-carcinoma * Sarcoma * Lymphoma * Immature teratoma * Melanoma By location * Pancoast tumor * Solitary pulmonary nodule * Central lung * Peripheral lung * Bronchial leiomyoma Pleura * Mesothelioma * Malignant solitary fibrous tumor * v * t * e Connective/soft tissue tumors and sarcomas Not otherwise specified * Soft-tissue sarcoma * Desmoplastic small-round-cell tumor Connective tissue neoplasm Fibromatous Fibroma/fibrosarcoma: * Dermatofibrosarcoma protuberans * Desmoplastic fibroma Fibroma/fibromatosis: * Aggressive infantile fibromatosis * Aponeurotic fibroma * Collagenous fibroma * Diffuse infantile fibromatosis * Familial myxovascular fibromas * Fibroma of tendon sheath * Fibromatosis colli * Infantile digital fibromatosis * Juvenile hyaline fibromatosis * Plantar fibromatosis * Pleomorphic fibroma * Oral submucous fibrosis Histiocytoma/histiocytic sarcoma: * Benign fibrous histiocytoma * Malignant fibrous histiocytoma * Atypical fibroxanthoma * Solitary fibrous tumor Myxomatous * Myxoma/myxosarcoma * Cutaneous myxoma * Superficial acral fibromyxoma * Angiomyxoma * Ossifying fibromyxoid tumour Fibroepithelial * Brenner tumour * Fibroadenoma * Phyllodes tumor Synovial-like * Synovial sarcoma * Clear-cell sarcoma Lipomatous * Lipoma/liposarcoma * Myelolipoma * Myxoid liposarcoma * PEComa * Angiomyolipoma * Chondroid lipoma * Intradermal spindle cell lipoma * Pleomorphic lipoma * Lipoblastomatosis * Spindle cell lipoma * Hibernoma Myomatous general: * Myoma/myosarcoma smooth muscle: * Leiomyoma/leiomyosarcoma skeletal muscle: * Rhabdomyoma/rhabdomyosarcoma: Embryonal rhabdomyosarcoma * Sarcoma botryoides * Alveolar rhabdomyosarcoma * Leiomyoma * Angioleiomyoma * Angiolipoleiomyoma * Genital leiomyoma * Leiomyosarcoma * Multiple cutaneous and uterine leiomyomatosis syndrome * Multiple cutaneous leiomyoma * Neural fibrolipoma * Solitary cutaneous leiomyoma * STUMP Complex mixed and stromal * Adenomyoma * Pleomorphic adenoma * Mixed Müllerian tumor * Mesoblastic nephroma * Wilms' tumor * Malignant rhabdoid tumour * Clear-cell sarcoma of the kidney * Hepatoblastoma * Pancreatoblastoma * Carcinosarcoma Mesothelial * Mesothelioma * Adenomatoid tumor [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Solitary fibrous tumor	c1266119	29,885	wikipedia	https://en.wikipedia.org/wiki/Solitary_fibrous_tumor	2021-01-18T18:45:34	{"mesh": ["D054364"], "wikidata": ["Q7558248"]}
Adenocarcinoma of the lung Other namesPulmonary adenocarcinoma A gross pathological specimen of a pulmonary adenocarcinoma, removed in a lobectomy. SpecialtyOncology Adenocarcinoma of the lung is the most common type of lung cancer, and like other forms of lung cancer, it is characterized by distinct cellular and molecular features.[1] It is classified as one of several non-small cell lung cancers (NSCLC), to distinguish it from small cell lung cancer which has a different behavior and prognosis. Lung adenocarcinoma is further classified into several subtypes and variants.[2] The signs and symptoms of this specific type of lung cancer are similar to other forms of lung cancer, and patients most commonly complain of persistent cough and shortness of breath. Adenocarcinoma is more common in patients with a history of cigarette smoking, and is the most common form of lung cancer in younger women and Asian populations. The pathophysiology of adenocarcinoma is complicated, but generally follows a histologic progression from cells found in healthy lungs to distinctly dysmorphic, or irregular cells. There are several distinct molecular and genetic pathways that contribute to this progression. Like many lung cancers, adenocarcinoma of the lung is often advanced by the time of diagnosis. Once a lesion or tumor is identified with various imaging modalities, such as computed tomography (CT) or X-ray, a biopsy is required to confirm the diagnosis. Treatment of this lung cancer is based upon the specific subtype and the extent of spread from the primary tumor. Surgical resection, chemotherapy, radiotherapy, targeted therapy and immunotherapy are used in attempt to eradicate the cancerous cells based upon these factors.[3] ## Contents * 1 Signs and symptoms * 1.1 Extrapulmonary manifestations * 2 Causes * 2.1 Risk factors * 3 Mechanism * 3.1 Pathogenesis * 3.1.1 Gene mutations and copy number alterations * 3.1.2 Chromosomal rearrangements * 3.2 Pathophysiology * 4 Diagnosis * 4.1 Classification * 4.2 Imaging * 4.3 Histopathology * 5 Treatment * 5.1 Surgery * 5.2 Chemotherapy * 5.3 Radiotherapy * 5.4 Targeted therapy * 5.5 Immunotherapy * 6 Epidemiology * 7 References ## Signs and symptoms[edit] The majority of patients who are diagnosed with lung cancer usually present with locally advanced or metastatic disease. Only about one third of patients have stage I disease when diagnosed.[4] The symptoms that the patient exhibits usually reflect the extent of the cancer's spread. Lung cancers that are discovered early may cause symptoms localized to the respiratory system. However, lung cancer that is advanced will cause patients to experience additional signs and symptoms secondary to the cancer spreading to other organ systems.[5] In order of highest frequency, the most common signs of lung cancer include:[6] * cough that does not go away or gets worse * weight loss * dyspnea (shortness of breath or difficulty breathing) * chest pain, which may be aggravated by deep breathing, coughing, or laughing * hemoptysis (coughing up blood or rust-colored phlegm)[7] * bone pain * clubbing * fever * generally feeling tired or weak * superior vena cava obstruction- facial, neck, upper torso swelling. This is caused by compression of vasculature by the lung tumor that restricts blood return from the upper body.[4] * dysphagia (trouble swallowing or the sensation that something is caught in the throat) and hoarseness * new onset of wheezing without history of asthma Clinicians should have a high level of suspicion for lung cancer, especially in patients with a smoking history. Patients with recurring or unresolving lung infections (e.g. bronchitis and pneumonia) that are unresponsive to antibiotics should also be further evaluated for lung cancer. In nonsmokers, women and East Asians are more likely to present with symptoms of an underlying lung cancer at younger ages.[5] Importantly, many of these signs are commonly due to other causes that are not cancer.[6] A detailed medical history should be obtained from each patient to determine the relevance of further diagnostic workup and management.[citation needed] ### Extrapulmonary manifestations[edit] Adenocarcinoma, like other forms of lung cancer, is usually advanced or metastatic at time of diagnosis. Patients may complain of signs or symptoms outside of the respiratory tract that represent a hematologic or metabolic complication of the malignancy without, however, resulting necessarily from obstruction or metastasis. These go under the name of paraneoplastic syndromes, which often indicate advanced disease and worse prognosis[citation needed]. The most common paraneoplastic syndromes associated with adenocarcinoma of the lung are described below: * Hypercalcemia of malignancy is more common in squamous cell carcinoma of the lung, but can occur in adenocarcinoma as well. Parathyroid hormone-related peptide (PTHrP) is produced by tumor cells and functions similarly to parathyroid hormone (PTH). The production of this hormonally active peptide by cancer cells causes increased bone resorption via upregulation of osteoclasts, one of the cells responsible for bone remodeling. When bone is broken down, calcium is released into the bloodstream, resulting in hypercalcemia. The signs and symptoms of elevated calcium in the blood include: thirst, fatigue, constipation, polyuria (increased urination), and nausea. It is important to rule out boney metastases in patients with NSCLC because they also present with hypercalcemia. * Hypertrophic pulmonary osteoarthropathy (HPO) is fairly rare in adenocarcinoma. Less than 1% of patients with adenocarcinoma of the lung will exhibit this finding, but when it does occur, it is a poor prognostic factor. The exact mechanism of HPO is unknown but it thought to be hormonal or neurogenic in etiology. The triad of HPO includes distal clubbing, arthritis, and bilateral symmetrical periosteal formation.[4] ## Causes[edit] ### Risk factors[edit] According to the Nurses' Health Study, the risk of pulmonary adenocarcinoma increases substantially after a long duration of tobacco smoking: smokers with a previous smoking duration of 30–40 years are more than twice as likely to develop lung adenocarcinoma compared to never-smokers (relative risk of approximately 2.4); a duration of more than 40 years increases relative risk to 5.[8] This cancer usually is seen peripherally in the lungs, as opposed to small cell lung cancer and squamous cell lung cancer, which both tend to be more centrally located,[9][10] although it may also occur as central lesions.[10] For unknown reasons, it often arises in relation to peripheral lung scars. The current theory is that the scar probably occurred secondary to the tumor, rather than causing the tumor.[10] The adenocarcinoma has an increased incidence in smokers, and is the most common type of lung cancer seen in non-smokers and women.[10] Deeper inhalation of cigarette smoke results in peripheral lesions that are often the case in adenocarcinomas of the lung. Generally, adenocarcinoma grows more slowly and forms smaller masses than the other subtypes.[10] However, it tends to metastasize at an early stage.[10] ## Mechanism[edit] ### Pathogenesis[edit] Micrograph showing an ALK positive adenocarcinoma of the lung. ALK immunostain. Micrograph showing a ROS1 positive adenocarcinoma of the lung. ROS1 immunostain. Large scale studies such as The Cancer Genome Atlas (TCGA) have systematically characterized recurrent somatic alterations likely driving lung adenocarcinoma initiation and development.[11] #### Gene mutations and copy number alterations[edit] Since smoking is a strong mutagenic factor, lung adenocarcinoma is one of the tumor types with the highest number of mutations.[12] Common somatic mutations in lung adenocarcinoma affect many oncogenes and tumor suppressor genes, including TP53 (mutated in 46% of cases), EGFR (27%), KRAS (32%), KEAP1, STK11 and NF1.[3] EGFR and KRAS mutations tend to appear in a mutually exclusive fashion. KRAS mutations are associated with smoking habits, whereas EGFR mutations occur more frequently in females, people of Asian ethnicity and never-smokers.[2] Copy number amplifications in oncogenes such as TERT, MDM2, EGFR, MET, and MYC have been reported, as well as deletions of tumor suppressor genes such as CDKN2A.[11] Frequent alterations occur in genes belonging to the receptor tyrosine kinase pathway, of which EGFR is the most prominent example. This pathway is involved in cell proliferation and survival and it is often deregulated in cancer. As a consequence, targeted therapies have been developed to inhibit mutant pathway components.[11][13] #### Chromosomal rearrangements[edit] Three membrane associated tyrosine kinase receptors are recurrently involved in fusions or rearrangements in adenocarcinomas: ALK, ROS1, and RET, and more than eighty other translocations have also been reported in adenocarcinomas of the lung.[14] In ALK rearrangements, the most common partner gene is EML4.[3] EML4-ALK fusions tend to occur in tumors that do not carry EGFR or KRAS mutations and have also a lower frequency of TP53 mutations. ALK and ROS fusions offer opportunities for targeted therapies with tyrosine kinase inhibitors[citation needed]. ### Pathophysiology[edit] The respiratory tract can be divided into two main components: the conducting airways and the gas exchange airways. The gas exchange airways are made of alveoli, or small microscopic air sacs, that are responsible for the exchange of oxygen and carbon dioxide during normal respiration. Alveoli are composed of two cell types, type I and type II pneumocytes. Type I pneumocytes cover 95% of alveolar surfaces, and are not able to regenerate. Type II pneumocytes are more common, making up 60% of the cells within alveolar epithelium, but constitute only 3% of the alveolar surface.[15] There are several factors that contribute to the transformation of normal alveolar epithelium into dysplastic, or pre-cancerous, lesions. Adenocarcinoma of the lung develops in a step-wise progression as type II pneumocytes undergo consecutive molecular changes that disrupt normal cell regulation and turnover. Atypical adenomatous hyperplasia (AAH) is considered a pre-cancerous lesion, and is thought to further progress to adenocarcinoma in situ and invasive adenocarcinoma of the lung. The lesions of AAH are <5 mm, can be single or multiple, and have a ground glass appearance on CT imaging. As more genetic mutations and disregulation of normal cell signaling pathways accumulate, AAH can progress to adenocarcinoma in situ (AIS). AIS lesions are classified as small tumors <3 cm with abnormal type II pneumocyte cell growth that is limited to the alveolar spaces i.e. without invasion into the stroma, pleura, or vasculature. This type of growth is termed "lepidic" and is characteristic of adenocarcinoma of the lung in its earliest stages.[15] ## Diagnosis[edit] A diagnosis of lung cancer may be suspected on the basis of typical symptoms, particularly in a person with smoking history. Symptoms such as coughing up blood and unintentional weight loss may prompt further investigation, such as medical imaging. ### Classification[edit] CT scan- adenocarcinoma of the left lung The majority of lung cancers can be characterized as either small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC). Lung adenocarcinoma is one of the three major subtypes of NSCLC, which also include squamous carcinoma and large cell carcinoma.[15] Historically, there has been much debate in the most accurate method of describing adenocarcinoma of the lung and several revisions of classification systems have been published. Most recently, the International Multidisciplinary Classification of Lung Adenocarcinoma was published in 2011 and represents the consensus of several organizations to more accurately describe this specific type of lung cancer.[2] The current classification system aims to more reliably predict prognosis and determination of therapeutic management.[4] The tumor size, pattern of cell growth, and depth of cell invasion into normal lung tissue are considered in determining classification. The following names represent a step-wise pathologic progression in the natural course of adenocarcinoma development; Adenocarcinoma in situ (AIS), Minimally invasive adenocarcinoma (MIA), and Invasive adenocarcinoma.[15] Invasive adenocarcinoma of the lung includes a heterogenous mixture of subtypes and variants. The 2011 consensus describes five subtypes of invasive adenocarcinomas based on the cell pattern that is most predominant. These subtypes are described below: Histopathology of lepidic predominant adenocarcinoma. * lepidic predominant * acinar predominant * papillary predominant * micropapillary predominant * solid predominant with mucin production Cell patterns identifying subtypes are associated with prognosis, ranging from favorable (lepidic) to intermediate (acinar and papillary) to poor (micropapillary and solid).[2] Four discrete variants of invasive adenocarcinomas not assignable to these five subtypes are also included in the current classification: * invasive mucinous adenocarcinoma * colloid adenocarcinoma * fetal adenocarcinoma * enteric adenocarcinoma[4] ### Imaging[edit] A chest x-ray (radiograph) is often the first imaging test performed when a person presents with cough or chest pain, particularly in the primary care setting. A chest radiograph may detect a lung nodule/mass that is suggestive of cancer, although sensitivity and specificity are limited.[citation needed] CT imaging provides better evaluation of the lungs, with higher sensitivity and specificity for lung cancer compared to chest radiograph (although still significant false positive rate[16]). Computed tomography (CT) that is specifically aimed at evaluating lung cancer includes the chest and the upper abdomen. This allows for evaluation of other relevant anatomic structures such as nearby lymph nodes, adrenal glands, liver, and bones which may show evidence of metastatic spread of disease.[4] Indeed, the US Preventative Services Task Force recommends annual screening with low-dose CT in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years, with certain caveats (see Lung cancer screening).[17] Nuclear medicine imaging, such as PET/CT and bone scan, may also be helpful to diagnose and detect metastatic disease elsewhere in the body.[7] PET/CT uses a metabolically active tracer that allows clinicians to identify areas of the body that are hypermetabolic. Increased uptake of the tracer occurs in malignant cells and areas of inflammation or infection. Integrating the imaging reflective of metabolic activity with normal CT imaging allows for higher sensitivity and specificity compared to PET alone.[4] MRI is reserved for patients with advanced disease where intracranial, or brain, involvement is likely. It is also helpful for evaluating the extent of chest wall, diaphragmatic, brachial plexus (such as in the case of superior sulcus tumors), or spine involvement.[4] ### Histopathology[edit] If possible, a biopsy of any suspected lung tumor is performed in order to make a microscopic evaluation of the cells involved and is ultimately required to confirm diagnosis.[7] Biopsy should be attempted in distant lesions first to establish a histologic diagnosis and to simultaneously confirm metastatic staging. The biopsy material is also used to analyze whether the tumor express any specific mutations suitable for tageted therapy (eg. EGFR mutation or ALK mutation). Biopsy can be accomplished via bronchoscopy, transthoracic needle biopsy, and video-assisted thorascopic surgery (VATS).[4] While sputum cytology has been shown to have limited utility, thoracentesis, or aspiration of pleural fluid with an ultrasound-guided needle, should be performed when pleural effusion is present. When malignant cells are identified in the pleural aspirate of patients highly suspect for lung cancer, a definitive diagnosis and staging (stage IV adenocarcinoma of the lung) is established.[4] Adenocarcinoma of the lung tends to stain mucin positive as it is derived from the mucus-producing glands of the lungs. Similar to other adenocarcinoma, if this tumor is well differentiated (low grade) it will resemble the normal glandular structure. Poorly differentiated adenocarcinoma will not resemble the normal glands (high grade) and will be detected by seeing that they stain positive for mucin (which the glands produce). Adenocarcinoma can also be distinguished by staining for TTF-1, a cell marker for adenocarcinoma.[18] As discussed previously, the category of adenocarcinoma includes are range of subtypes, and any one tumor tends to be heterogeneous in composition. Several major subtypes are currently recognized by the World Health Organization (WHO)[1] and the International Association for the Study of Lung Cancer (IASLC) / American Thoracic Society (ATS) / European Respiratory Society (ERS):[19][20][21] lepidic predominant adenocarcinoma, acinar predominant adenocarcinoma, papillary predominant adenocarcinoma, micropapillary predominant adenocarcinoma, solid predominant adenocarcinoma, and solid predominant with mucin production. In as many as 80% of these tumors, components of more than one subtype will be recognized. Surgically resected tumors should be classified by comprehensive histological subtyping, describing patterns of involvement in increments of 5%. The predominant histologic subtype is then used to classify the tumor overall.[2] The predominant subtype is prognostic for survival after complete resection.[22] To reveal the adenocarcinomatous lineage of the solid variant, demonstration of intracellular mucin production may be performed. Foci of squamous metaplasia and dysplasia may be present in the epithelium proximal to adenocarcinomas, but these are not the precursor lesions for this tumor. Rather, the precursor of peripheral adenocarcinomas has been termed atypical adenomatous hyperplasia (AAH).[10] Microscopically, AAH is a well-demarcated focus of epithelial proliferation, containing cuboidal to low-columnar cells resembling club cells or type II pneumocytes.[10] These demonstrate various degrees of cytologic atypia, including hyperchromasia, pleomorphism, prominent nucleoli.[10] However, the atypia is not to the extent as seen in frank adenocarcinomas.[10] Lesions of AAH are monoclonal, and they share many of the molecular aberrations (like KRAS mutations) that are associated with adenocarcinomas.[10] Signet ring and clear cell adenocarcinoma are no longer histological subtypes, but rather cytological features that can occur in tumour cells of multiple histological subtypes, most often solid adenocarcinoma.[19] ## Treatment[edit] The treatment of adenocarcinoma of the lung depends on several factors including stage, resectability, performance status, histology and genomic alterations acquired by the individual tumor.[23] As in most cancer types, treatment approaches can be broadly divided into 5 categories: surgery, chemotherapy, radiotherapy, targeted therapy and immunotherapy.[citation needed] ### Surgery[edit] Early stage (I, II and IIIA) lung adenocarcinomas are typically treated surgically to remove the tumor with pneumonectomy or lobectomy, if it is found to be resectable with imaging studies and biopsies and if the patient is considered able to tolerate surgery.[10] Video-assisted thorascopic surgery (VATS) is often adopted, which consists in the insertion of a thorascope inside a small incision made in the chest; a lobe can be removed via the scope through this small incision.[23] Incidence of adenocarcinoma of the lung (in yellow) as compared to other lung cancer types, with fractions of non-smokers versus smokers shown for each type.[24] ### Chemotherapy[edit] For advanced (stage IV) and unresectable lung tumors, the first-line therapy is platinum-based doublet chemotherapy, combining cisplatin or carboplatin with another cytotoxic agent.[3] Regimens strongly depend on each patient performance status and response, and when the risk of adverse events could worsen quality of life significantly, basic supportive care is more recommended. Chemotherapy is also used as an adjuvant therapy following surgery to kill remaining cancer cells in patients with stage IIA, IIB and IIIA NSCLC.[23] ### Radiotherapy[edit] Adenocarcinoma is a non-small cell lung carcinoma, and it is not as responsive to radiation therapy compared to small cell lung carcinoma.[10] However, radiotherapy may be used as an adjuvant therapy for patients who have undergone a resection surgery to reduce the risk of lung cancer relapse. It may also benefit inoperable tumors that are localized to the chest and be part of palliative care to improve quality of life in patients not responding to surgery or chemotherapy.[23] ### Targeted therapy[edit] Targeted therapy is available for lung adenocarcinomas with certain molecular characteristics. Tyrosine kinase inhibitors (TKIs) have been developed to target mutant components of the receptor tyrosine kinase pathway such as EGFR, ALK[25] and ROS1, which show frequent alterations in lung adenocarcinomas. First-generation EGFR TKIs, including gefitinib and erlotinib, have been shown to be more effective in treating EGFR-mutated patients with respect to cytotoxic chemotherapy. Second-generation inhibitors such as afatinib and dacomitinib provided a broader scope of application as they are able to target not only the protein EGFR itself but also other members of the EGFR family, such as HER2 and HER4 (also known as ERBB2 and ERBB4), and they have shown improved progression-free survival compared to gefitinib. As the most common cause of acquired resistance to first-generation TKIs is a second EGFR mutation on codon 790, a third-generation EGFR TKI, osimertinib, has been developed to target this new mutation as well.[3] MET amplification is another known mechanism of acquired resistance.[2] ALK inhibitors such as crizotinib showed to be effective against tumors harboring ALK fusions. Most patients previously treated with crizotinib benefited from second-generation ALK inhibitors including ceritinib, alectinib and brigatinib. Resistance to ALK inhibitors can occur with novel acquired ALK mutations or amplifications.[3] Also ROS1-positive tumors have shown high sensitivity to ALK inhibitors due to the high homology between the kinase domains of ROS1 and ALK.[3] ### Immunotherapy[edit] Immune response can be prevented via activation of immune checkpoints, which consist in the binding of a ligand protein (e.g. PD-L1) to a receptor (e.g. PD-1) on the immune cell surface. As a consequence, cancer cells expressing PD-L1 can inactivate T cells thus fostering tumor growth. Immune checkpoint inhibitors have been developed to restore T cell-mediated antitumor immunity by blocking either the ligand or the receptor.[citation needed] Immune checkpoint inhibitors have been approved for NSCLC, including anti-PD-1 nivolumab and pembrolizumab. Anti-PD-1 agents are used for patients with advanced NSCLC whose tumors progress after first-line cytotoxic chemotherapy. Pembrolizumab was established as a new standard of care for patients with advanced or metastatic NSCLC with high PD-L1 expression levels, and responses are even more pronounced for tumor with a high mutational burden (i.e. having an elevated number of mutations).[3] Therapeutic approaches combining multiple immune checkpoint inhibitors or one immune checkpoint inhibitors and a cytotoxic agent are undergoing clinical trials as of 2018.[3][26] The potential role of anti-PD-1 agents as neoadjuvant therapy in resectable NSCLCs is also being investigated.[27] ## Epidemiology[edit] As for other lung cancer subtypes, lung adenocarcinoma incidence is strongly associated with smoking. Incidence of pulmonary adenocarcinoma has been increasing in many developed Western nations in the past few decades, with a share reaching 43.3% of all lung cancers in the US as of 2012,[28] thus replacing squamous cell lung carcinoma as the most common type of lung cancer. This can be largely attributed to the decreasing smoking rates, which favors the adenocarcinoma histology. Indeed, although smoking is still its strongest risk factor, lung adenocarcinoma is by far the most common among lifelong non-smokers (<100 cigarettes in a lifetime).[29] ## References[edit] 1. ^ a b Travis WD, Brambilla E, Müller-Hermelink HK, Harris CC, eds. (2004). Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart (PDF). World Health Organization Classification of Tumours. Lyon: IARC Press. ISBN 978-92-832-2418-1. Archived from the original (PDF) on 2009-08-23. Retrieved 27 March 2010. 2. ^ a b c d e f Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, et al. (February 2011). "International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma". Journal of Thoracic Oncology. 6 (2): 244–85. doi:10.1097/JTO.0b013e318206a221. PMC 4513953. PMID 21252716. 3. ^ a b c d e f g h i Boshoff, Chris; Morgensztern, Daniel; Herbst, Roy S. (2018-01-24). "The biology and management of non-small cell lung cancer". Nature. 553 (7689): 446–454. Bibcode:2018Natur.553..446H. doi:10.1038/nature25183. ISSN 1476-4687. PMID 29364287. S2CID 4463109. 4. ^ a b c d e f g h i j editor., Grippi, Michael A. (2015-04-14). Fishman's pulmonary diseases and disorders. ISBN 9780071807289. OCLC 898053564.CS1 maint: extra text: authors list (link) 5. ^ a b Horn L, Pao W, Johnson DH (2012). "Chapter 89". In Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL, Loscalzo J (eds.). Harrison's Principles of Internal Medicine (18th ed.). McGraw-Hill. ISBN 978-0-07-174889-6. 6. ^ a b "Non-Small Cell Lung Cancer Signs and Symptoms". Cancer.org. American Cancer Society. May 16, 2016. Retrieved March 11, 2018. 7. ^ a b c "Tests for Non-Small Cell Lung Cancer". American Cancer Society. June 23, 2017. Retrieved March 11, 2018. 8. ^ Kenfield SA, Wei EK, Stampfer MJ, Rosner BA, Colditz GA (June 2008). "Comparison of aspects of smoking among the four histological types of lung cancer". Tobacco Control. 17 (3): 198–204. doi:10.1136/tc.2007.022582. PMC 3044470. PMID 18390646. 9. ^ Travis WD, Travis LB, Devesa SS (January 1995). "Lung cancer". Cancer. 75 (1 Suppl): 191–202. doi:10.1002/1097-0142(19950101)75:1+<191::AID-CNCR2820751307>3.0.CO;2-Y. PMID 8000996. 10. ^ a b c d e f g h i j k l m Mitchell RS, Kumar V, Abbas AK, Fausto N (2007). "Chapter 13, box on morphology of adenocarcinoma". Robbins Basic Pathology (8th ed.). Philadelphia: Saunders. ISBN 978-1-4160-2973-1. 11. ^ a b c The Cancer Genome Atlas Research Network (July 2014). "Comprehensive molecular profiling of lung adenocarcinoma". Nature. 511 (7511): 543–550. Bibcode:2014Natur.511..543T. doi:10.1038/nature13385. ISSN 1476-4687. PMC 4231481. PMID 25079552. 12. ^ Mariamidze, Armaz; Aredes, Natália D.; Lee, Jung Il; Rubin, Mark A.; Westervelt, Peter; Tine, Brian Van; Ley, Timothy; Heath, Sharon; Govindan, Ramaswamy (2018-03-28). "Scalable Open Science Approach for Mutation Calling of Tumor Exomes Using Multiple Genomic Pipelines". Cell Systems. 6 (3): 271–281.e7. doi:10.1016/j.cels.2018.03.002. ISSN 2405-4712. PMC 6075717. PMID 29596782. 13. ^ Reference, Genetics Home. "Lung cancer". Genetics Home Reference. Retrieved 2019-05-06. 14. ^ http://atlasgeneticsoncology.org/Tumors/TranslocLungAdenocarcID6751.html 15. ^ a b c d Brunicardi. (2014). Schwartz's Principles of Surgery, 10e. McGraw-Hill. OCLC 941117341. 16. ^ Gossner J (April 2014). "Lung cancer screening-don't forget the chest radiograph". World Journal of Radiology. 6 (4): 116–8. doi:10.4329/wjr.v6.i4.116. PMC 4000607. PMID 24778773. 17. ^ U.S. Preventive Services Task Force (December 2016). "Final Recommendation Statement: Lung Cancer: Screening". Retrieved 2018-03-10. 18. ^ World Cancer Report 2014. World Health Organization. 2014. pp. Chapter 5.1. ISBN 978-9283204299. 19. ^ a b Van Schil PE, Asamura H, Rusch VW, Mitsudomi T, Tsuboi M, Brambilla E, Travis WD (February 2012). "Surgical implications of the new IASLC/ATS/ERS adenocarcinoma classification". The European Respiratory Journal. 39 (2): 478–86. doi:10.1183/09031936.00027511. PMID 21828029. 20. ^ Travis WD, Brambilla E, Van Schil P, Scagliotti GV, Huber RM, Sculier JP, Vansteenkiste J, Nicholson AG (August 2011). "Paradigm shifts in lung cancer as defined in the new IASLC/ATS/ERS lung adenocarcinoma classification". The European Respiratory Journal. 38 (2): 239–43. doi:10.1183/09031936.00026711. PMID 21804158. 21. ^ Vazquez M, Carter D, Brambilla E, Gazdar A, Noguchi M, Travis WD, Huang Y, Zhang L, Yip R, Yankelevitz DF, Henschke CI (May 2009). "Solitary and multiple resected adenocarcinomas after CT screening for lung cancer: histopathologic features and their prognostic implications". Lung Cancer. 64 (2): 148–54. doi:10.1016/j.lungcan.2008.08.009. PMC 2849638. PMID 18951650. 22. ^ Russell PA, Wainer Z, Wright GM, Daniels M, Conron M, Williams RA (September 2011). "Does lung adenocarcinoma subtype predict patient survival?: A clinicopathologic study based on the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international multidisciplinary lung adenocarcinoma classification". Journal of Thoracic Oncology. 6 (9): 1496–504. doi:10.1097/JTO.0b013e318221f701. PMID 21642859. S2CID 26574271. 23. ^ a b c d Zappa, Cecilia; Mousa, Shaker A. (2016-06-23). "Non-small cell lung cancer: current treatment and future advances". Translational Lung Cancer Research. 5 (3): 288–300–300. doi:10.21037/tlcr.2016.06.07. ISSN 2226-4477. PMC 4931124. PMID 27413711. 24. ^ Smokers defined as current or former smoker of more than 1 year of duration. See image page in Commons for percentages in numbers. Reference: * Table 2 in: Kenfield SA, Wei EK, Stampfer MJ, Rosner BA, Colditz GA (June 2008). "Comparison of aspects of smoking among the four histological types of lung cancer". Tobacco Control. 17 (3): 198–204. doi:10.1136/tc.2007.022582. PMC 3044470. PMID 18390646. 25. ^ Arbour, Kathryn C.; Riely, Gregory J. (February 2017). "Diagnosis and Treatment of ALK Positive NSCLC". Hematology/Oncology Clinics of North America. 31 (1): 101–111. doi:10.1016/j.hoc.2016.08.012. ISSN 0889-8588. PMC 5154547. PMID 27912826. 26. ^ Hellmann, Matthew D.; Ciuleanu, Tudor-Eliade; Pluzanski, Adam; Lee, Jong Seok; Otterson, Gregory A.; Audigier-Valette, Clarisse; Minenza, Elisa; Linardou, Helena; Burgers, Sjaak (2018-05-31). "Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden". New England Journal of Medicine. 378 (22): 2093–2104. doi:10.1056/NEJMoa1801946. ISSN 0028-4793. PMC 7193684. PMID 29658845. 27. ^ Forde, Patrick M.; Chaft, Jamie E.; Smith, Kellie N.; Anagnostou, Valsamo; Cottrell, Tricia R.; Hellmann, Matthew D.; Zahurak, Marianna; Yang, Stephen C.; Jones, David R. (2018-05-24). "Neoadjuvant PD-1 Blockade in Resectable Lung Cancer". New England Journal of Medicine. 378 (21): 1976–1986. doi:10.1056/NEJMoa1716078. ISSN 0028-4793. PMC 6223617. PMID 29658848. 28. ^ "Browse the Tables and Figures - SEER Cancer Statistics Review (CSR) 1975-2012". SEER. Retrieved 2019-02-22. 29. ^ Gandara, D. R.; Hammerman, P. S.; Sos, M. L.; Lara, P. N.; Hirsch, F. R. (2015-05-15). "Squamous Cell Lung Cancer: From Tumor Genomics to Cancer Therapeutics". Clinical Cancer Research. 21 (10): 2236–2243. doi:10.1158/1078-0432.CCR-14-3039. ISSN 1078-0432. PMC 4862209. PMID 25979930. * v * t * e Glandular and epithelial cancer Epithelium Papilloma/carcinoma * Small-cell carcinoma * Combined small-cell carcinoma * Verrucous carcinoma * Squamous cell carcinoma * Basal-cell carcinoma * Transitional cell carcinoma * Inverted papilloma Complex epithelial * Warthin's tumor * Thymoma * Bartholin gland carcinoma Glands Adenomas/ adenocarcinomas Gastrointestinal * tract: Linitis plastica * Familial adenomatous polyposis * pancreas * Insulinoma * Glucagonoma * Gastrinoma * VIPoma * Somatostatinoma * Cholangiocarcinoma * Klatskin tumor * Hepatocellular adenoma/Hepatocellular carcinoma Urogenital * Renal cell carcinoma * Endometrioid tumor * Renal oncocytoma Endocrine * Prolactinoma * Multiple endocrine neoplasia * Adrenocortical adenoma/Adrenocortical carcinoma * Hürthle cell Other/multiple * Neuroendocrine tumor * Carcinoid * Adenoid cystic carcinoma * Oncocytoma * Clear-cell adenocarcinoma * Apudoma * Cylindroma * Papillary hidradenoma Adnexal and skin appendage * sweat gland * Hidrocystoma * Syringoma * Syringocystadenoma papilliferum Cystic, mucinous, and serous Cystic general * Cystadenoma/Cystadenocarcinoma Mucinous * Signet ring cell carcinoma * Krukenberg tumor * Mucinous cystadenoma / Mucinous cystadenocarcinoma * Pseudomyxoma peritonei * Mucoepidermoid carcinoma Serous * Ovarian serous cystadenoma / Pancreatic serous cystadenoma / Serous cystadenocarcinoma / Papillary serous cystadenocarcinoma Ductal, lobular, and medullary Ductal carcinoma * Mammary ductal carcinoma * Pancreatic ductal carcinoma * Comedocarcinoma * Paget's disease of the breast / Extramammary Paget's disease Lobular carcinoma * Lobular carcinoma in situ * Invasive lobular carcinoma Medullary carcinoma * Medullary carcinoma of the breast * Medullary thyroid cancer Acinar cell * Acinic cell carcinoma * v * t * e Cancer involving the respiratory tract Upper RT Nasal cavity Esthesioneuroblastoma Nasopharynx Nasopharyngeal carcinoma Nasopharyngeal angiofibroma Larynx Laryngeal cancer Laryngeal papillomatosis Lower RT Trachea * Tracheal tumor Lung Non-small-cell lung carcinoma * Squamous-cell carcinoma * Adenocarcinoma (Mucinous cystadenocarcinoma) * Large-cell lung carcinoma * Rhabdoid carcinoma * Sarcomatoid carcinoma * Carcinoid * Salivary gland–like carcinoma * Adenosquamous carcinoma * Papillary adenocarcinoma * Giant-cell carcinoma Small-cell carcinoma * Combined small-cell carcinoma Non-carcinoma * Sarcoma * Lymphoma * Immature teratoma * Melanoma By location * Pancoast tumor * Solitary pulmonary nodule * Central lung * Peripheral lung * Bronchial leiomyoma Pleura * Mesothelioma * Malignant solitary fibrous tumor [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Adenocarcinoma of the lung	c0152013	29,886	wikipedia	https://en.wikipedia.org/wiki/Adenocarcinoma_of_the_lung	2021-01-18T18:52:30	{"gard": ["5742"], "mesh": ["D000077192", "C538231"], "umls": ["C0152013", "C1335060"], "wikidata": ["Q843799"]}
Not to be confused with enophthalmos. In medicine, enophthalmia describes eyes that are abnormally sunken into their sockets.[1] This condition usually affects elderly persons. Surgery can be done to correct it. Bilateral progressive enophthalmos may be the presenting sign of metastatic breast carcinoma, even when local symptoms in the breast are absent. ## References[edit] 1. ^ Gelatt, Kirk N.; Gelatt, Janice P. (2011). Veterinary Ophthalmic Surgery – E-Book. Elsevier Health Sciences. ISBN 978-0702048937. Retrieved 23 November 2017. ## Further reading[edit] * Camirand A, Doucet J, Harris J (November 1997). "Anatomy, pathophysiology, and prevention of senile enophthalmia and associated herniated lower eyelid fat pads". Plast. Reconstr. Surg. 100 (6): 1535–1546. doi:10.1097/00006534-199711000-00026. PMID 9385969. * Gonçalves AC, Moura FC, Monteiro ML (July 2005). "Bilateral progressive enophthalmos as the presenting sign of metastatic breast carcinoma". Ophthal Plast Reconstr Surg. 21 (4): 311–313. doi:10.1097/01.iop.0000167786.00697.0b. PMID 16052150. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Enophthalmia	c0423224	29,887	wikipedia	https://en.wikipedia.org/wiki/Enophthalmia	2021-01-18T18:46:50	{"umls": ["C0423224"], "wikidata": ["Q5379401"]}
A number sign (#) is used with this entry because of evidence that Primrose syndrome (PRIMS) is caused by heterozygous mutation in the ZBTB20 gene (606025) on chromosome 3q13. Description Primrose syndrome consists of recognizable facial features, macrocephaly, mental retardation, enlarged and calcified external ears, sparse body hair, and distal muscle wasting (summary by Carvalho and Speck-Martins, 2011). Patients with a deletion syndrome involving 3q13.31 (615433) exhibit features overlapping those of Primrose syndrome. Clinical Features Primrose (1982) described the single case of a 33-year-old male with mental retardation who had been institutionalized from the age of 12 years. The parents were not related. He showed progressive wasting of the distal muscles of the legs and later of the small muscles of the hands. The cartilage of each pinna was extensively ossified, and photographs showing a fracture were presented. Cystic changes were observed in the head of the humerus and of the femurs, with deformity or destruction of the articular surfaces. Bilateral circumscribed, whitish, paracentral posterior polar cataracts were also described. He had had recurrent attacks of bilateral otitis media and was somewhat deaf. There was a 'hard mass filling in the cavity of the hard palate' which was not radioopaque. The same condition may have been described by Collacott et al. (1986). Their patient had large, calcified pinnae, and the buccal cavity was reduced by a large, soft-tissue mass extending over the inferior surface of the hard palate. Both lower limbs were wasted distally, and the hands were small and wasted. He had had recurrent attacks of otitis media and was profoundly deaf; he had dense bilateral cataracts. Lindor et al. (1996) described a third affected male who also had schizophrenia. Mathijssen et al. (2006) described a mentally retarded adult man who had joint contractures, sparse body hair, hearing loss, dysmorphic facial features, and, as cardinal features suggesting Primrose syndrome, large calcified pinnae and a huge torus palatinus. In addition, he developed a germ cell tumor of his right testicle at age 27 years. It was uncertain whether an increased risk of malignancy forms part of this syndrome or is only a consequence of cryptorchidism in the patient reported. Dalal et al. (2010) reported a 43-year-old woman with all the clinical elements of Primrose syndrome who remained undiagnosed for over 4 decades. She was born with congenital heart disease, hip dysplasia, and agenesis of the corpus callosum. In childhood, she was noted to have hearing impairment, cataracts, neoplasm of the bone in the palate, ossification of cartilage, cystic bone changes, diabetes mellitus, and hypothyroidism. She walked at age 6 years and was severely mentally retarded. She slowly lost the ability to walk, had distal muscle wasting, and needed a wheelchair by age 40. She had dysmorphic facial features, including micrognathia, anteverted nares, prominent ears and nasal root, ptosis, and microphthalmia. She also had spastic paraparesis, areflexia, motor tics, hand stereotypies, and self-flagellating behaviors. Brain MRI showed partial calcification of the basal ganglia, and laboratory studies showed increase serum calcitonin. Microarray analysis detected a small 225.5-kb deletion on chromosome 11p between rs12275693 and rs1442927 encompassing the BBOX1 gene (603312). Dalal et al. (2010) postulated an abnormality in calcium homeostasis. Carvalho and Speck-Martins (2011) described a 23-year-old Brazilian man, born of nonconsanguineous parents, who had mental retardation and developmental delay, macrocephaly, wide forehead, broad face, deeply set eyes, downslanting palpebral fissures with mild ptosis, large ears, high nasal bridge, large jaw, and apparently small mouth. The ears were unusually firm and immobile. He had thoracic kyphosis but no scoliosis, and genu valgum with distal muscle wasting of the lower extremities was apparent. Ankles and elbows had mild reduction of mobility. He also displayed sparse body hair and thin, dystrophic fingernails and toenails. There was scaly, thickened skin over extensor joint surfaces, and a great number of pigmented nevi as well as some striae were present. Examination at 23 years of age showed poor coordination and mild bradykinesia, but follow-up over 2 decades did not reveal progressive neurologic involvement. Hearing loss was not clinically noticeable, but audiometric evaluation detected a bilateral moderate mixed hearing loss. Skeletal x-rays showed calcification of the ear cartilages, thoracic kyphosis, and sloping ribs; osteopenia was not noted. CT of the head revealed uniform and extensive calcification of both pinnae and part of the external ear canals, with no brain calcification. Echocardiography showed signs of concentric left ventricular remodeling. Carvalho and Speck-Martins (2011) reviewed the key features of the 7 reported patients with Primrose syndrome, noting that all cases had been sporadic, with no familial occurrence or consanguinity. Posmyk et al. (2011) reported a 27-year-old man with Primrose syndrome who had only mild mental retardation. He also exhibited hypergonadotropic hypogonadism and low bone density due to progressive osteoporosis. Posmyk et al. (2011) stated that their findings confirmed that Primrose syndrome is a progressive neurodegenerative disorder with late-onset neurologic signs. Cordeddu et al. (2014) studied 8 individuals with Primrose syndrome, 5 of whom had previously been described in detail (Battisti et al., 2002; Mathijssen et al., 2006; Dalal et al., 2010; Carvalho and Speck-Martins, 2011; Posmyk et al., 2011), and all of whom had mutations in the ZBTB20 gene. Mutation-positive patients exhibited a consistent phenotype characterized by increased growth, variable intellectual disability, autistic traits and other behavioral problems, hypotonia, and distinctive facial features overlapping with the phenotype of the 3q13.31 deletion syndrome (615433). However, the phenotype in the Primrose syndrome patients was more severe, including disturbances of glucose metabolism with insulin-resistant diabetes occurring in adulthood, distal muscle wasting resulting in contractures in adulthood, and hearing loss and ectopic calcification of the ears and brain during puberty or early adulthood. Battisti et al. (2002) reported a 49-year-old woman who exhibited the classic features of Primrose syndrome, associated with late-onset progressive gait ataxia, pyramidal signs, and cerebral calcification. Neurologic examination revealed severe mental retardation, frequent confabulation, severely impaired spastic-ataxic gait, positive Romberg sign, slight hypertonia, mild muscular atrophy of the limbs, upper limb areflexia, brisk tendon reflexes in the legs, bilateral ankle clonus, and Babinski sign. Brain CT showed areas of dense calcification in both heads of the caudate nuclei, with less dense calcification in both globi pallidi and in the anterior limb of the left internal capsule; dense calcification of both external ears was also evident. Muscle biopsy was suggestive of neurogenic atrophy. The authors noted that this was the first reported case of a female patient with Primrose syndrome, and suggested that the diagnosis should be considered in patients with syndromic mental retardation plus progressive neurologic involvement, including cerebral calcification, ataxia, and peripheral neuropathy. Mattioli et al. (2016) studied a 4-year-old boy, ascertained from a cohort of patients with developmental delay, in whom targeted sequencing of candidate genes revealed mutations in the ZBTB20 gene. Reverse phenotyping showed that the patient presented the classic features of Primrose syndrome, including dysmorphic facies, macrocephaly, hearing loss, hypotonia, and hypoplasia of the corpus callosum. His ears were large, but were supple to palpation with no evidence of calcification; the authors noted that calcified pinnae had only been observed in adult cases. In addition, the proband had congenital hypothyroidism, and thyroid scan showed a large volume thyroid gland with homogeneous uptake suggesting a problem in thyroid hormone synthesis. Mattioli et al. (2016) noted that 1 other patient with Primrose syndrome had been reported to have hypothyroidism (Dalal et al., 2010). Grimsdottir et al. (2019) reported a 14-year old boy with many features of Primrose syndrome, including macrocephaly, intellectual disability, agenesis of the corpus callosum, hearing impairment, and characteristic facial dysmorphology, and a mutation in the ZBTB20 gene. Facial features included downslanting palpebral fissures, low-set ears, flat hypoplastic midface with maxillary retrognathia, relative mandibular prognathism, and a narrow and tapered lower face and chin. The patient also had short stature and did not respond sufficiently to growth hormone therapy. Craniofacial and dental findings not previously reported in Primrose syndrome included large paranasal sinuses, narrow cranial base, decreased cranial base angle, maxillary hypoplasia, a supernumerary tooth, and retention of 2 mandibular premolars. Inheritance All reported cases of Primrose syndrome have been sporadic (Lindor et al., 1996). Molecular Genetics In 4 unrelated patients with Primrose syndrome, including the patients reported by Mathijssen et al. (2006), Dalal et al. (2010), and Carvalho and Speck-Martins (2011), Cordeddu et al. (2014) performed whole-exome sequencing and identified heterozygosity for de novo missense variants in the ZBTB20 gene (see, e.g., 606025.0001 and 606025.0002); subsequent mutation analysis in 4 more affected individuals, including the patients reported by Battisti et al. (2002) and Posmyk et al. (2011), revealed a heterozygous ZBTB20 missense mutation in each (see, e.g., 606025.0003 and 606025.0004). Functional analysis showed strongly reduced DNA binding for all mutants compared to wildtype, and results were consistent with the mutations having a dominant-negative impact on the wildtype allele. The authors noted that the more severe phenotype seen in Primrose syndrome patients compared to that of patients with 3q13.31 deletion syndrome, who exhibit overlapping but milder features, was in line with a dominant-negative effect of the ZBTB20 mutations compared to the haploinsufficiency that likely underlies the 3q13.31 deletion syndrome. By targeted exome sequencing of 275 genes known to be or potentially associated with intellectual disability in a cohort of individuals with mild to severe developmental delay, who were negative for pathogenic CNV by array-CGH, Mattioli et al. (2016) identified a 4-year-old boy with Primrose syndrome who was heterozygous for 2 de novo missense mutations on the same allele of the ZBTB20 gene (606025.0005). In a 14-year-old boy with Primrose syndrome, Grimsdottir et al. (2019) identified heterozygosity for a de novo missense mutation in the ZBTB20 gene (H600Q; 606025.0006). The mutation was found by exome sequencing and confirmed by Sanger sequencing. INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature Weight \- Weight above the 90th percentile \- Truncal obesity HEAD & NECK Head \- Macrocephaly \- Brachycephaly Face \- Midface hypoplasia \- Wide forehead \- Large jaw Ears \- Ossification of pinnae \- Large pinnae \- Superiorly displaced ears \- Hearing loss Eyes \- Posterior polar cataracts \- Downslanting palpebral fissures \- Deep-set eyes \- Ptosis Mouth \- Prominent lower lip \- Small mouth \- Downturned corners of mouth CHEST External Features \- Narrow chest Ribs Sternum Clavicles & Scapulae \- Downward sloping ribs \- Pectus excavatum Breasts \- Gynecomastia GENITOURINARY Internal Genitalia (Male) \- Cryptorchidism, bilateral (in some patients) SKELETAL \- Joint contractures (fingers, hips, knees) \- Generalized osteoporosis Skull \- Macrocephaly \- Brachycephaly \- Basilar impression \- Maxillary hypoplasia Spine \- Kyphosis \- Endplate irregularities \- Posterior scalloping of vertebral bodies Pelvis \- Narrow iliac wings \- Flexion contractures (hips) Limbs \- Genu valgum \- Flexion contractures (knees) \- Cystic bone lesions Hands \- Short terminal phalanges Feet \- Pes cavus \- Metatarsus varus \- Flexed toes SKIN, NAILS, & HAIR Nails \- Dystrophic fingernails and toenails Hair \- Absent facial, axillary, body hair \- Sparse scalp hair MUSCLE, SOFT TISSUES \- Distal muscle wasting NEUROLOGIC Central Nervous System \- Mental retardation \- Neurodegeneration \- Hypotonia \- Hypoplastic corpus callosum \- Intracerebral calcifications (in some patients) Behavioral Psychiatric Manifestations \- Autism (in some patients) \- Self-injurious behavior (in some patients) \- Aggression (rare) \- Tics or anxieties (rare) \- Repetitive compulsive movements (rare) \- Phobias (rare) \- Restlessness (rare) \- Frequent confabulation (rare) ENDOCRINE FEATURES \- Abnormal glucose tolerance test \- Insulin-resistant diabetes mellitus in adulthood \- Congenital hypothyroidism (in some patients) \- Hypergonadotropic hypogonadism (rare) MISCELLANEOUS \- Some features are variably present MOLECULAR BASIS \- Caused by mutation in the zinc finger and BTB-domain containing 20 gene (ZBTB20, 606025.0001 ) ▲ 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	PRIMROSE SYNDROME	c0796121	29,888	omim	https://www.omim.org/entry/259050	2019-09-22T16:23:55	{"mesh": ["C536420"], "omim": ["259050"], "orphanet": ["3042"], "synonyms": ["Alternative titles", "OSSIFIED EAR CARTILAGES WITH MENTAL DEFICIENCY, MUSCLE WASTING, AND BONY CHANGES"]}
A rare bone disease characterized by avascular necrosis of the navicular bone in children. Patients present with sudden unexplained foot pain, inability to bear weight, and limping. Radiographic features include flattening, fragmentation, and patchy sclerosis of the navicular bone. Soft tissue swelling may be associated. The condition is most commonly unilateral and self-limiting. Boys are more often affected than girls. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Osteochondrosis of the tarsal bone	c0022765	29,889	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=563991	2021-01-23T18:23:20	{"mesh": ["D055034"], "synonyms": ["Aseptic necrosis of the tarsal bone", "Avascular necrosis of the tarsal bone", "Kohler disease"]}
## Summary ### Clinical characteristics. Succinic semialdehyde dehydrogenase (SSADH) deficiency is characterized by infantile-onset hypotonia, developmental delay, cognitive impairment, expressive language deficit, and mild ataxia. Epilepsy is present in about half of affected individuals and is more common in adults. Hyperkinetic behavior, aggression, self-injurious behaviors, hallucinations, and sleep disturbances have been reported in nearly half of all affected individuals, more commonly in those who are older. Basal ganglia signs including choreoathetosis, dystonia, and myoclonus have been reported in a few individuals with earlier-onset, more severe disease. Involvement beyond the central nervous system has not been described. Individuals with SSADH deficiency typically have 4-hydroxybutyric aciduria present on urine organic acid analysis. Head MRI reveals T2 hyperintensities in multiple regions, involving the globus pallidi, cerebellar dentate nuclei, subthalamic nuclei, subcortical white matter, and brain stem, as well as cerebral and sometimes cerebellar atrophy. EEG findings include background slowing and spike discharges that are usually generalized. ### Diagnosis/testing. The diagnosis of SSADH deficiency is established by the identification of biallelic pathogenic variants in ALDH5A1. ### Management. Treatment of manifestations: Management is most often symptomatic, directed at the treatment of seizures and neurobehavioral disturbances. A broad spectrum of antiepileptic medication has been used to treat this condition. While vigabatrin is an irreversible inhibitor of GABA-transaminase and thus inhibits the formation of succinic semialdehyde, it has shown inconsistent results in treatment of seizures associated with SSADH deficiency. Methylphenidate, thioridazine, risperidal, fluoxetine, and benzodiazepines have been used for treatment of increased anxiety, aggressiveness, and inattention. Additional, non-pharmacologic treatments may include physical and occupational therapy, sensory integration, feeding and/or speech therapy. Surveillance: Regular neurologic and developmental assessments as indicated. Agents/circumstances to avoid: Valproate may inhibit residual SSADH enzyme activity; however, valproate may be considered in individuals with refractory epilepsy who have failed other treatments. ### Genetic counseling. SSADH deficiency is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives is possible if the pathogenic variants have been identified in the family. Biochemical testing is not accurate or reliable for carrier determination. Prenatal diagnosis for pregnancies at increased risk is possible using molecular genetic testing if the pathogenic variants have been identified in the family, or using biochemical testing (either measurement of 4-hydroxybutyric acid in amniotic fluid or assay of SSADH enzyme activity in chorionic villus tissue and cultured amniocytes). ## Diagnosis ### Suggestive Findings Succinic semialdehyde dehydrogenase (SSADH) deficiency should be suspected in individuals with the following clinical, imaging, EEG, and supportive laboratory findings: Clinical features. Late-infantile to early-childhood onset, slowly progressive or static encephalopathy characterized by: * Cognitive deficiency * Prominent expressive language deficit * Hypotonia * Epilepsy * Hyporeflexia * Ataxia Neuroimaging features * Cranial MRI that demonstrates: * A pallidodentatoluysian pattern [Pearl et al 2009c], showing increased T2-weighted signal involving the globus pallidi bilaterally and symmetrically, in addition to the cerebellar dentate nuclei and subthalamic nuclei * T2-hyperintensities of subcortical white matter and brain stem * Cerebral atrophy * Cerebellar atrophy * Delayed myelination * Magnetic resonance spectroscopy that demonstrates elevated levels of GABA and related compounds in the Glx peak (e.g., GHB [gammahydroxybutyrate, also known as 4-hydroxybutyric acid], glutamate, and homocarnosine) EEG findings. Background slowing and spike discharges that are usually generalized. Note: EEG studies are normal in about one third of affected individuals. Supportive laboratory findings * Absence of metabolic acidosis * Urine organic acid analysis * 4-hydroxybutyric acid concentration of 100-1200 mmol/mol creatinine (normal: >0-7 mmol/mol creatinine) * Note: (1) Specific ion monitoring may be required for the detection of this metabolite, as its presence is sometimes obscured by a large normal urea peak on routine organic acid qualitative studies [Pearl et al 2003]; (2) falsely elevated urinary concentrations of 4-hydroxybutyric acid (GHB) have been reported in individuals in whom the urine sample was obtained using Coloplast SpeediCath catheters, which have been found to have GHB concentrations as high as 11 mmol/L [Wamelink et al 2011]. * Small amounts of 4,5-dihydroxyhexanoic acid and 3-hydroxyproprionic acid and significant amounts of dicarboxylic acids may be detected. Urine organic acids can be confusing with the presence of elevated levels of d-2-hydroxyglutaric acid, but in the routine organic acid analysis this will only be reported as 2-hydroxyglutaric acid. * Increased glycine concentration * Plasma amino/organic acid analysis * 4-hydroxybutyric acid concentration of 35-600 µmol/L (normal: 0-3 µmol/L) * Increased glycine concentration * Cerebrospinal fluid (CSF) analysis * 4-hydroxybutyric acid concentration of 100-850 µmol/L (normal: 0-2 µmol/L) * A transient increase in CSF glycine concentration * Elevated free and total GABA and homocarnosine concentrations coupled to lowered glutamine Note: Newborn screening is not routinely done for this disorder at this time. ### Establishing the Diagnosis The diagnosis of SSADH deficiency is established in a proband by the identification of biallelic pathogenic variants in ALDH5A1 on molecular genetic testing (see Table 1). Molecular testing approaches can include single-gene testing or use of a multigene panel: * Single-gene testing. Sequence analysis of ALDH5A1 is performed first, followed by gene-targeted deletion/duplication analysis if only one or no pathogenic variant is found. * A multigene panel that includes ALDH5A1 and other genes of interest (see Differential Diagnosis) may also be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. ### Table 1. Molecular Genetic Testing Used in Succinic Semialdehyde Dehydrogenase Deficiency View in own window Gene 1Test MethodProportion of Probands with Pathogenic Variants 2 Detectable by This Method ALDH5A1Sequence analysis 397% 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\. Sixty-two families [Liu et al 2016] 5\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 6\. Kwok et al [2012] reported a novel 34-bp insertion in exon 10 that resulted in a pathogenic frameshift variant leading to a truncated SSADH protein lacking 50 amino acids in the C-terminus. ## Clinical Characteristics ### Clinical Description SSADH deficiency is characterized by a relatively non-progressive encephalopathy presenting with hypotonia and delayed acquisition of motor and language developmental milestones in the first two years of life. Common clinical features include intellectual disability, behavior problems, and motor dysfunction. Symptoms are first reported at a mean age of 11 months (range 0-44 months) and the mean age at diagnosis is 6.6 years (range 0-25 years) [Pearl et al 2009a]. One study reported an adult man who was diagnosed in the sixth decade of life [Lapalme-Remis et al 2015]. Psychiatric symptoms may be the most disabling; they include sometimes prominent ADHD and even aggression in early childhood, and anxiety and obsessive-compulsive disorder in adolescence and adulthood [Pearl & Gibson 2004, Knerr et al 2008]. Affected individuals do not usually have episodic decompensation following metabolic stressors as is typical of other organic acidemias and metabolic encephalopathies, although some have been diagnosed after having unanticipated difficulty recovering from otherwise ordinary childhood illnesses. Clinical presentation with acute onset of generalized hypotonia and choreiform movement following upper-respiratory tract infection has been reported [Wang et al 2016]. Approximately 10% of affected individuals have a more severe phenotype including early-onset prominent extrapyramidal manifestations and a regressive course [Pearl et al 2005b]. Seizures. Half of affected individuals have epilepsy, usually with generalized tonic-clonic or atypical absence seizures [Pearl et al 2003]. Epilepsy is more common in adults, and may be progressive [Lapalme-Remis et al 2015]. In one family two heterozygotes for SSADH deficiency (one parent and a sib of a proband with the disorder) had generalized spike-wave discharges, photosensitivity, and absence and myoclonic seizures [Dervent et al 2004]. Sleep disorders are common and manifest either as excessive daytime somnolence or as disorders of initiating or maintaining sleep [Philippe et al 2004, Arnulf et al 2005]. Ten affected individuals studied with overnight polysomnography and daytime multiple sleep latency testing (MLST) had prolonged REM latency (mean 272±89 min) and reduced stage REM percentage (mean 8.9%, range 0.3%-13.8%) [Pearl et al 2009b]. Half of these individuals showed a decrease in daytime mean sleep latency on MSLT, indicating excessive daytime somnolence. Overall, REM sleep appears to be reduced. Neuropathology from one individual with a confirmed diagnosis revealed discoloration of the globus pallidus and leptomeningeal congestion on gross pathology. On microscopic examination, hyperemia and granular perivascular calcification of the globus pallidus and superior colliculus were identified, and interpreted as consistent with chronic excitotoxic injury. There was not significant neuronal loss or gliosis of CA1 of the hippocampus, the area that would have been considered most vulnerable to epileptic or hypoxic injury in this individual, who died with a clinical diagnosis of SUDEP (sudden unexpected death in epilepsy patients) after having had escalating seizures [Knerr et al 2010]. The authors are aware of two additional affected individuals who had SUDEP [Authors, unpublished data]. ### Genotype-Phenotype Correlations No genotype-phenotype correlations have been observed. ### Prevalence Approximately 450 individuals have been diagnosed with SSADH deficiency [Gibson & Jakobs 2001; Gibson & Jakobs, personal communication], but it has been estimated to occur in 1:1,000,000 individuals [KM Gibson, unpublished data]. Because of the nonspecific nature of SSADH deficiency and the related difficulty in diagnosing affected individuals, the disorder may be significantly underdiagnosed. Thus, the true prevalence is unknown [Pearl et al 2003]. Parental consanguinity has been reported in approximately 40% of all published cases [Gibson et al 1997a, Gibson et al 1997b, Al-Essa et al 2000, Yalçinkaya et al 2000]. ## Differential Diagnosis Other disorders of GABA metabolism: * 4-aminobutyrate aminotransferase (GABA-transaminase, GABA-T) deficiency (OMIM 613163). GABA transaminase deficiency was first reported in an index sibship and an additional unrelated proband [Medina-Kauwe et al 1999], and then in an infant identified using MR spectroscopy [Tsuji et al 2010]. The phenotype is characterized by psychomotor retardation, hypotonia, hyperreflexia, lethargy, refractory seizures of neonatal or infantile onset, agenesis of the corpus callosum, and cerebellar hypoplasia. Additional cases are being recognized especially with increased use of next-generation sequencing [Besse et al 2015]. Free and total GABA concentration levels are elevated in the CSF, without elevation in GHB. Biallelic pathogenic variants in ABAT are causative. Inheritance is autosomal recessive. * Homocarnosinosis (OMIM 236130). Homocarnosine is a dipeptide of histidine and GABA. A single case of primary homocarnosinosis has been reported; the enzyme defect has not been conclusively proven [Gibson & Jakobs 2001]. SSADH deficiency cannot easily be differentiated clinically from other disorders that cause intellectual disability. Screening by urine organic acid analysis is necessary to detect SSADH deficiency. Elevated glycine can be seen in glycine encephalopthy (non-ketotic hyperglycinemia), which is distinguished from SSADH based on the absence of GHB in individuals with glycine encephalopathy. Abnormal signal bilaterally in the globus pallidus can be seen in other organic acidurias, particularly methylmalonic aciduria (see Methylmalonic Acidemia), mitochondrial disorders (see Mitochondrial Disorders Overview), pantothenate kinase-associated neurodegeneration (PKAN), and neuroferritinopathy [Curtis et al 2001]. Unlike other metabolic encephalopathies and some other organic acidurias, SSADH deficiency does not usually present with metabolic stroke, megalencephaly, episodic hypoglycemia, hyperammonemia, acidosis, or intermittent decompensation [Pearl et al 2003]. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with succinic semialdehyde dehydrogenase (SSADH) deficiency, the following evaluations are recommended: * Neuroimaging (MRI) * EEG * Developmental evaluation * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations The management of SSADH deficiency is most often symptomatic, directed at the treatment of seizures and neurobehavioral disturbances. Seizures. Antiseizure medications employed for the treatment of SSADH deficiency tend to be broad spectrum, although valproate is avoided when possible because of inhibition of potential residual enzymatic activity [Shinka et al 2003]. Vigabatrin, an irreversible inhibitor of GABA-transaminase, inhibits the formation of succinic semialdehyde [Matern et al 1996]. However, vigabatrin has shown inconsistent results [Howells et al 1992, Gropman 2003], suggesting that it is not effective at inhibiting peripheral GABA-transaminase, leading to a peripheral supply of 4-hydroxybutyric acid to the brain and thus decreasing its own efficacy. Brain MRI signal changes, particularly prominent in the thalamus and basal ganglia, have been seen in infants treated with relatively high doses of vigabatrin [Pearl et al 2009c]. However, reports of uncontrolled, nonblinded trials of vigabatrin in two affected children described a decrease in plasma GHB concentrations and clinical improvement (specifically in verbal communication) in one child age eight years [Casarano et al 2012] and slow clinical improvement (although not unexpected based on natural history) in a child age 2.5 years [Escalera et al 2010]. Neurobehavioral symptoms. Methylphenidate, thioridazine, risperidal, fluoxetine, and benzodiazepines have been used for the treatment of increased anxiety, aggressiveness, and inattention [Gibson et al 2003]. Beneficial non-pharmacologic treatments include physical therapy directed at developing strength, endurance, and balance; occupational therapy for improvement of fine motor skills, feeding, and sensory integration; and speech therapy [Gropman 2003]. ### Surveillance Regular neurologic and developmental assessments are indicated. ### Agents/Circumstances to Avoid Valproate is generally contraindicated as it may inhibit residual SSADH enzyme activity [Shinka et al 2003]. However, Vanadia et al [2013] reported an individual with SSADH deficiency who had refractory epilepsy after possible limbic encephalitis. The refractory epilepsy was finally controlled with magnesium valproate. One year after initiation of magnesium valproate therapy, the affected individual remained seizure free and had marked behavioral improvements, including decreases in aggression, coprolalia, and non-recognition of danger. In addition, the EEG demonstrated improved background organization. ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation Biomarkers have been studied with plans for utilization in clinical trials. Positron emission tomography (PET) with [11C]flumazenil (FMZ), a benzodiazepine receptor antagonist, showed reduced binding in cortical, basal ganglia, and cerebellar regions of interest versus controls consistent with downregulation of GABA receptors [Pearl et al 2007]. Transcranial magnetic stimulation similarly showed downregulation of GABAergic activity in affected individuals versus controls [Pearl et al 2009a]. A single case of improvement in gait, coordination, and energy was reported as an abstract in a 30-month-old male administered 200 mg/kg/day of taurine [Saronwala et al 2008]. However, an open-label study of eighteen individuals with SSADH deficiency treated with taurine did not show significant improvement in adaptive behavior scores. This study was assigned a class IV level of evidence because it did not involve a control group [Pearl et al 2014]. SGS-742, a GABA-B receptor antagonist, demonstrated in the murine model a significant effect on electrocorticography when compared with topiramate [Pearl et al 2009a]. Liver-mediated gene therapy in the mouse model did lead to reductions in GHB levels in liver, kidney, serum, and brain extracts [Gupta et al 2004]. A clinical trial of SGS-742 is currently enrolling (ClinicalTrials.gov). Recent data demonstrated that administration of rapamycin to an SSADH-deficient mouse model reduced mTOR activity, reduced the elevated numbers of mitochondria in the liver and brain (due to improved mitophagy), and normalized aberrant antioxidant levels; mTOR inhibitors such as rapamycin may lead to the treatment of many diseases, including SSADH [Lakhani et al 2014]. Search ClinicalTrials.gov in the US and www.ClinicalTrialsRegister.eu in Europe for access to information on clinical studies for a wide range of diseases and conditions. ### Other Animal experiments utilizing the murine model have demonstrated partial efficacy involving the amino acid taurine, vigabatrin, and GABAB and GHB receptor inhibitors [Gupta et al 2004]. A murine trial has demonstrated some efficacy of the ketogenic diet [Nylen et al 2008], although the mechanism of the observed changes (and thus the potential for success in a human trial) is unknown [Knerr & Pearl 2008]. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Succinic Semialdehyde Dehydrogenase Deficiency	c0268631	29,890	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1195/	2021-01-18T20:53:34	{"mesh": ["C535803"], "synonyms": ["4-Hydroxybutyric Aciduria", "Gamma-Hydroxybutyric Aciduria", "SSADH Deficiency"]}
Not to be confused with Atrioventricular reentrant tachycardia. AV-nodal reentrant tachycardia Other namesAtrioventricular-nodal reentrant tachycardia An example of an ECG tracing typical of uncommon AV nodal reentrant tachycardia. Highlighted in yellow is the P wave that falls after the QRS complex. SpecialtyCardiology SymptomsPalpitations, chest tightness, neck pulsation Diagnostic methodelectrocardiogram, electrophysiological study Differential diagnosisAtrioventricular reentrant tachycardia, focal atrial tachycardia, junctional ectopic tachycardia Treatmentvagal manoeuvres, adenosine, ablation Medicationadenosine, calcium channel antagonists, beta blockers, flecainide AV-nodal reentrant tachycardia (AVNRT) is a type of abnormal fast heart rhythm. It is a type of supraventricular tachycardia (SVT), meaning that it originates from a location within the heart above the bundle of His. AV nodal reentrant tachycardia is the most common regular supraventricular tachycardia. It is more common in women than men (approximately 75% of cases occur in females). The main symptom is palpitations. Treatment may be with specific physical maneuvers, medications, or, rarely, synchronized cardioversion. Frequent attacks may require radiofrequency ablation, in which the abnormally conducting tissue in the heart is destroyed. AVNRT occurs when a reentrant circuit forms within or just next to the atrioventricular node. The circuit usually involves two anatomical pathways: the fast pathway and the slow pathway, which are both in the right atrium. The slow pathway (which is usually targeted for ablation) is located inferior and slightly posterior to the AV node, often following the anterior margin of the coronary sinus. The fast pathway is usually located just superior and posterior to the AV node. These pathways are formed from tissue that behaves very much like the AV node, and some authors regard them as part of the AV node. The fast and slow pathways should not be confused with the accessory pathways that give rise to Wolff-Parkinson-White syndrome (WPW syndrome) or atrioventricular reciprocating tachycardia (AVRT). In AVNRT, the fast and slow pathways are located within the right atrium close to or within the AV node and exhibit electrophysiologic properties similar to AV nodal tissue. Accessory pathways that give rise to WPW syndrome and AVRT are located in the atrioventricular valvular rings. They provide a direct connection between the atria and ventricles, and have electrophysiologic properties similar to muscular heart tissue of the heart's ventricles. ## Contents * 1 Signs and symptoms * 2 Mechanisms * 2.1 Typical AVNRT * 2.2 Atypical AVNRT * 3 Diagnosis * 4 Treatment * 4.1 Arrhythmia termination * 4.2 Arrhythmia prevention * 5 References * 6 External links ## Signs and symptoms[edit] The main symptom of AVNRT is the sudden development of rapid regular palpitations.[1] These palpitations may be associated with a fluttering sensation in the neck, caused by near-simultaneous contraction of the atria and ventricles against a closed tricuspid valve leading to the pressure or atrial contraction being transmitted backwards into the venous system.[2] The rapid heart rate may lead to feelings of anxiety, and may therefore be mistaken for panic attacks.[2] In some cases, the onset of the fast heart is associated with a brief drop in blood pressure. When this happens, someone may experience dizziness or rarely lose consciousness (faint).[3] Someone with underlying coronary artery disease (narrowing of the arteries of the heart by atherosclerosis) who has a very rapid heart rate may experience chest pain similar to angina; this pain is band- or pressure-like around the chest and often radiates to the left arm and angle of the left jaw.[3] Symptoms often occur without any specific trigger, although some find that their palpitations often occur after lifting heavy items or bending forwards.[1] The onset of palpitations is sudden, with the acceleration of the heart rate occurring within a single beat, and may be preceded by a feeling of the heart skipping a beat. The heart may continue to race for minutes or hours, but the eventual termination of the arrhythmia is as rapid as its onset.[1] During AVNRT the heart rate is typically between 140 and 280 beats per minute.[3] Close inspection of the neck may reveal pulsation of the jugular vein in the form of "cannon A-waves" as the right atrium contracts against a closed tricuspid valve.[2] ## Mechanisms[edit] During typical AVNRT, electrical impulses travel down the slow pathway of the AV node and back up the fast pathway. The fundamental mechanism of AVNRT is a re-entrant circuit within the atrioventricular node. This can take several forms. "Typical", "common", or "slow-fast" AVNRT uses the slow AV nodal pathway to conduct towards the ventricle (the anterograde limb of the circuit) and the fast AV nodal pathway to conduct to the atria (the retrograde limb). The re-entrant circuit can be reversed such that the fast AV nodal pathway is the anterograde limb and the slow AV nodal pathway is the retrograde limb, referred to as "atypical", "uncommon", or "fast-slow" AVNRT. Atypical AVNRT may also use the slow AV nodal pathway as the anterograde limb and left atrial fibres that approach the AV node from the left side of the inter-atrial septum as the retrograde limb, and is sometimes referred to as "slow-slow" AVNRT.[4] ### Typical AVNRT[edit] In typical AVNRT, the anterograde conduction is via the slow pathway and the retrograde conduction is via the fast pathway ("slow-fast" AVNRT). Because the retrograde conduction is via the fast pathway, stimulation of the atria (which produces the inverted P wave) occurs very soon after stimulation of the ventricles (which causes the QRS complex). As a result, the time from the QRS complex to the P wave (the RP interval) is short, less than 50% of the time between consecutive QRS complexes. The RP interval is often so short that the inverted P waves may not be seen on the surface electrocardiogram (ECG) as they are buried within or immediately after the QRS complexes, appearing as a "pseudo R prime" wave in lead V1 or a "pseudo S" wave in the inferior leads.[5] ### Atypical AVNRT[edit] In atypical AVNRT, the anterograde conduction is via the fast pathway and the retrograde conduction is via the slow pathway ("fast-slow" AVNRT).[5] Multiple slow pathways can exist so that both anterograde and retrograde conduction are over slow pathways. ("slow-slow" AVNRT). Because the retrograde conduction is via the slow pathway, stimulation of the atria will be delayed by the slow conduction tissue and will typically produce an inverted P wave that falls after the QRS complex on the surface ECG. ## Diagnosis[edit] If the symptoms are present while the person is receiving medical care (e.g., in an emergency department), an ECG may show typical changes that confirm the diagnosis ie, QRS duration <120 ms, unless a heart block is suspected.[6] If the palpitations are recurrent, a doctor may request a Holter monitor (portable, wearable ECG recorder). Again, this will show the diagnosis if the recorder is attached at the time of the symptoms. In rare cases, disabling but infrequent episodes of palpitations may require the insertion of a small device under the skin that continuously record heart activity (an implantable loop recorder). All these ECG-based technologies also enable the distinction between AVNRT and other abnormal fast heart rhythms such as atrial fibrillation, atrial flutter, sinus tachycardia, ventricular tachycardia and tachyarrhythmias related to Wolff-Parkinson-White syndrome, all of which may have symptoms that are similar to AVNRT. Blood tests commonly performed in people with palpitations are: * thyroid function tests (TFTs) – an overactive thyroid increases the risk of AVNRT * electrolytes – disturbances in potassium, calcium and magnesium may predispose to AVNRT * cardiac markers – if there is a concern that myocardial infarction (heart attack) has occurred either as a cause or as a result of the AVNRT; this is usually only the case if the patient has experienced chest pain ## Treatment[edit] Treatments for AVNRT aim to terminate episodes of tachycardia, and to prevent further episodes from occurring in the future. These treatments include physical manoeuvres, medication, and invasive procedures such as ablation.[7] ### Arrhythmia termination[edit] AVNRT termination following administration of adenosine An episode of supraventricular tachycardia due to AVNRT can be terminated by any action that transiently blocks the AV node. Some of those with AVNRT may be able to stop their attack by using physical manoeuvres that increase the activity of the vagus nerve on the heart, specifically on the atrioventricular node. These manoeuvres include carotid sinus massage (pressure on the carotid sinus in the neck) and the Valsalva manoeuvre (increasing the pressure in the chest by attempting to exhale against a closed airway by bearing down or holding one's breath).[8] Medications that slow or briefly halt electrical conduction through the AV node can terminate AVNRT, including adenosine, beta blockers, or non-dihydropyridine calcium channel blockers (such as verapamil or diltiazem).[8] Both adenosine and beta blockers may cause tightening of the airways, and are therefore used with caution in people who are known to have asthma. Less commonly used drugs for this purpose include antiarrhythmic drugs such as flecainide or amiodarone.[7] If the fast heart rate is poorly tolerated (e.g. the development of heart failure symptoms, low blood pressure or coma) then AVNRT can be terminated electrically using a cardioversion. In this procedure, after administering a strong sedative or general anaesthetic, an electric shock is applied to the heart to restore a normal rhythm.[7] ### Arrhythmia prevention[edit] While preventative treatment may be very helpful at stopping the unpleasant symptoms associated with AVNRT, as this arrhythmia is a benign condition, preventative treatment is not essential.[7] Some of those who choose not to have further treatment will eventually become asymptomatic.[7] Those who wish to have further treatment can choose to take long term antiarrhythmic medication. The first line drugs are calcium channel antagonists and beta blockers, with second line agents including flecainide, amiodarone, and occasionally digoxin. These drugs are moderately effective at preventing further episodes but need to be taken long term.[7] Alternatively, an invasive procedure called an electrophysiology (EP) study and catheter ablation can be used to confirm the diagnosis and potentially offer a cure. This procedure involves introducing wires or catheters into the heart through a vein in the leg.[2] The tip of one of these catheters can be used to heat or freeze the slow pathway of the AV node, destroying its ability to conduct electrical impulses, and preventing AVNRT.[9] The risks and benefits are weighed up before this is performed. Catheter ablation of the slow pathway, if successfully carried out, can potentially cure AVNRT with success rates of >95%, balanced against a small risk of complications including damaging the AV node and subsequently requiring a pacemaker.[7] ## References[edit] 1. ^ a b c Rosero, Spencer (2015), "A Brief Overview of Supraventricular Tachycardias", in Huang, MD, David T.; Prinzi, MD, Travis (eds.), Clinical Cardiac Electrophysiology in Clinical Practice, In Clinical Practice, Springer London, pp. 37–53, doi:10.1007/978-1-4471-5433-4_3, ISBN 9781447154327 2. ^ a b c d Ayala-Paredes, Félix; Roux, Jean-Francois; Verdu, Mariano Badra (2014), Kibos, Ambrose S.; Knight, Bradley P.; Essebag, Vidal; Fishberger, Steven B. (eds.), "AVNRT Ablation: Significance of Anatomic Findings and Nodal Physiology", Cardiac Arrhythmias, Springer London, pp. 387–400, doi:10.1007/978-1-4471-5316-0_30, ISBN 9781447153153 3. ^ a b c Hafeez, Yamama; Armstrong, Tyler J. (2019), "Atrioventricular Nodal Reentry Tachycardia (AVNRT)", StatPearls, StatPearls Publishing, PMID 29763111, retrieved 2019-08-15 4. ^ "Atrioventricular Nodal Reentrant Tachycardia (AVNRT)". 2009-09-30. 5. ^ a b Shen, Sharon; Knight, Bradley P. (2014), Kibos, Ambrose S.; Knight, Bradley P.; Essebag, Vidal; Fishberger, Steven B. (eds.), "How to Differentiate Between AVRT, AT, AVNRT, and Junctional Tachycardia Using the Baseline ECG and Intracardiac Tracings", Cardiac Arrhythmias, Springer London, pp. 199–208, doi:10.1007/978-1-4471-5316-0_15, ISBN 9781447153153 6. ^ Demosthenes G Katritsis, A John Camm (2010). "Atrioventricular nodal reentrant tachycardia". Circulation. 122 (8): 831–40. doi:10.1161/CIRCULATIONAHA.110.936591. PMID 20733110.CS1 maint: uses authors parameter (link) 7. ^ a b c d e f g Page, Richard L.; Joglar, José A.; Caldwell, Mary A.; Calkins, Hugh; Conti, Jamie B.; Deal, Barbara J.; Estes, N. A. Mark; Field, Michael E.; Goldberger, Zachary D. (May 2016). "2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society". Journal of the American College of Cardiology. 67 (13): e27–e115. doi:10.1016/j.jacc.2015.08.856. ISSN 1558-3597. PMID 26409259. 8. ^ a b Brubaker, Sarah; Long, Brit; Koyfman, Alex (February 2018). "Alternative Treatment Options for Atrioventricular-Nodal-Reentry Tachycardia: An Emergency Medicine Review". The Journal of Emergency Medicine. 54 (2): 198–206. doi:10.1016/j.jemermed.2017.10.003. ISSN 0736-4679. PMID 29239759. 9. ^ Kumar, Darpan S.; Dewland, Thomas A.; Balaji, Seshadri; Henrikson, Charles A. (May 2017). "How to Approach Difficult Cases of AVNRT". Current Treatment Options in Cardiovascular Medicine. 19 (5): 34. doi:10.1007/s11936-017-0531-9. ISSN 1092-8464. PMID 28374333. S2CID 21354961. ## External links[edit] Classification D * ICD-10: I47.1 * ICD-9-CM: 427.89 * MeSH: D013611 External resources * eMedicine: med/2955 ped/2535 * v * t * e Cardiovascular disease (heart) Ischaemic Coronary disease * Coronary artery disease (CAD) * Coronary artery aneurysm * Spontaneous coronary artery dissection (SCAD) * Coronary thrombosis * Coronary vasospasm * Myocardial bridge Active ischemia * Angina pectoris * Prinzmetal's angina * Stable angina * Acute coronary syndrome * Myocardial infarction * Unstable angina Sequelae * hours * Hibernating myocardium * Myocardial stunning * days * Myocardial rupture * weeks * Aneurysm of heart / Ventricular aneurysm * Dressler syndrome Layers Pericardium * Pericarditis * Acute * Chronic / Constrictive * Pericardial effusion * Cardiac tamponade * Hemopericardium Myocardium * Myocarditis * Chagas disease * Cardiomyopathy * Dilated * Alcoholic * Hypertrophic * Tachycardia-induced * Restrictive * Loeffler endocarditis * Cardiac amyloidosis * Endocardial fibroelastosis * Arrhythmogenic right ventricular dysplasia Endocardium / valves Endocarditis * infective endocarditis * Subacute bacterial endocarditis * non-infective endocarditis * Libman–Sacks endocarditis * Nonbacterial thrombotic endocarditis Valves * mitral * regurgitation * prolapse * stenosis * aortic * stenosis * insufficiency * tricuspid * stenosis * insufficiency * pulmonary * stenosis * insufficiency Conduction / arrhythmia Bradycardia * Sinus bradycardia * Sick sinus syndrome * Heart block: Sinoatrial * AV * 1° * 2° * 3° * Intraventricular * Bundle branch block * Right * Left * Left anterior fascicle * Left posterior fascicle * Bifascicular * Trifascicular * Adams–Stokes syndrome Tachycardia (paroxysmal and sinus) Supraventricular * Atrial * Multifocal * Junctional * AV nodal reentrant * Junctional ectopic Ventricular * Accelerated idioventricular rhythm * Catecholaminergic polymorphic * Torsades de pointes Premature contraction * Atrial * Junctional * Ventricular Pre-excitation syndrome * Lown–Ganong–Levine * Wolff–Parkinson–White Flutter / fibrillation * Atrial flutter * Ventricular flutter * Atrial fibrillation * Familial * Ventricular fibrillation Pacemaker * Ectopic pacemaker / Ectopic beat * Multifocal atrial tachycardia * Pacemaker syndrome * Parasystole * Wandering atrial pacemaker Long QT syndrome * Andersen–Tawil * Jervell and Lange-Nielsen * Romano–Ward Cardiac arrest * Sudden cardiac death * Asystole * Pulseless electrical activity * Sinoatrial arrest Other / ungrouped * hexaxial reference system * Right axis deviation * Left axis deviation * QT * Short QT syndrome * T * T wave alternans * ST * Osborn wave * ST elevation * ST depression * Strain pattern Cardiomegaly * Ventricular hypertrophy * Left * Right / Cor pulmonale * Atrial enlargement * Left * Right * Athletic heart syndrome Other * Cardiac fibrosis * Heart failure * Diastolic heart failure * Cardiac asthma * Rheumatic fever [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	AV nodal reentrant tachycardia	c0039232	29,891	wikipedia	https://en.wikipedia.org/wiki/AV_nodal_reentrant_tachycardia	2021-01-18T19:03:40	{"mesh": ["D013611"], "icd-9": ["427.89"], "icd-10": ["I47.1"], "wikidata": ["Q300123"]}
Micturation-induced seizures is a rare neurologic disease characterized by tonic posturing or clonic movements triggered by micturition, with bilateral or unilateral involvement of the extremities and with or without loss of consciousness. Developmental delay is reported in some cases. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Micturation-induced seizures	None	29,892	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=166430	2021-01-23T16:52:53	{"icd-10": ["G40.5"]}
A number sign (#) is used with this entry because of evidence that Paganini-Miozzo syndrome (MRXSPM) is caused by hemizygous mutation in the HS6ST2 gene (300545) on chromosome Xq26. One such family has been reported. Description Paganini-Miozzo syndrome (MRXSPM) is a neurodevelopmental disorder characterized by global developmental delay, impaired intellectual development, high myopia, and mild dysmorphic facial features (summary by Paganini et al., 2019) Clinical Features Paganini et al. (2019) reported 2 monozygotic Italian twin brothers with a syndromic neurodevelopmental disorder. The 2 boys and their unaffected brother, who were part of a triplet dichorionic-triamniotic pregnancy resulting from in vitro fertilization, were born at 30 weeks' gestation due to fetal distress. The 2 affected boys showed severely delayed psychomotor development, with walking at age 2 years and poor speech at age 5. Both had high myopia at -6 diopters, compared to -0.75 diopters for their unaffected brother, as well as chorioretinopathy. The affected boys also had febrile seizures in the first year of life that later resolved; brain imaging showed mildly enlarged lateral ventricles. Mild dysmorphic features included triangular face, large forehead, deep-set eyes, downslanting palpebral fissures and eyebrows, thin lips with downturned corners of the mouth, slight prognathism, pointed chin, and small, low-set, malrotated ears. At age 10 years, the patients had feeding difficulties and urinary incontinence. Laboratory studies showed mildly increased serum lactate and low glycemic scores. Inheritance The transmission pattern of MRXSPM in the family reported by Paganini et al. (2019) was consistent with X-linked recessive inheritance. Molecular Genetics In 2 Italian monozygotic twin brothers with MRXSPM, Paganini et al. (2019) identified a hemizygous missense mutation in the HS6ST2 gene (G306R; 300545.0001). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was inherited from the unaffected mother and was not present in the unaffected brother. The variant was not found in the dbSNP, 1000 Genomes Project, or ExAC databases. Molecular modeling predicted that the mutation could change the structure of the enzyme, causing both a modification of enzyme activity as well as intracellular mislocalization of the protein. In vitro functional expression studies in HEK293 cells showed that the mutant protein was expressed normally, but had significantly reduced enzymatic activity (about 40% compared to wildtype). Paganini et al. (2019) noted that low heparan sulfate sulfation levels have been implicated in defective development of the mammalian visual system. INHERITANCE \- X-linked recessive HEAD & NECK Face \- Large forehead \- Triangular face \- Prognathism, mild Ears \- Low-set ears \- Malrotated ears \- Small ears Eyes \- High myopia (-6 diopters) \- Chorioretinopathy \- Deep-set eyes \- Downslanted palpebral fissures \- Downslanted eyebrows Mouth \- Thin lips \- Downturned corners of the mouth ABDOMEN Gastrointestinal \- Poor feeding GENITOURINARY Bladder \- Urinary incontinence NEUROLOGIC Central Nervous System \- Global developmental delay \- Delayed walking, mild \- Impaired intellectual development \- Delayed speech \- Poor speech \- Febrile seizures \- Enlarged lateral ventricles LABORATORY ABNORMALITIES \- Increased serum lactate, mild MISCELLANEOUS \- Two Italian brothers have been reported (last curated June 2019) MOLECULAR BASIS \- Caused by mutation in the heparan sulfate 6-O-sulfotransferase 2 gene (HS6ST2, 300545.0001 ) ▲ 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	PAGANINI-MIOZZO SYNDROME	None	29,893	omim	https://www.omim.org/entry/301025	2019-09-22T16:18:55	{"omim": ["301025"], "synonyms": ["Alternative titles", "MENTAL RETARDATION, X-LINKED, SYNDROMIC, PAGANINI-MIOZZO TYPE"]}
Myxosarcoma SpecialtyOncology Myxosarcoma is a rare malignant tumor of the heart.[1] ## References[edit] 1. ^ Takami Y, Masumoto H, Terasawa A, Kanai M, Sugiura H (2007). "Left atrial myxosarcoma with previously detected intestinal metastasis". Tex Heart Inst J. 34 (1): 122–5. PMC 1847916. PMID 17420810. ## External links[edit] Classification D * ICD-O: 8840/3 * MeSH: D009236 * 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 This article about a neoplasm 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	Myxosarcoma	c0027155	29,894	wikipedia	https://en.wikipedia.org/wiki/Myxosarcoma	2021-01-18T19:05:12	{"mesh": ["D009236"], "umls": ["C0027155"], "wikidata": ["Q6949370"]}
Syndrome of shellfish poisoning Paralytic shellfish poisoning The saxitoxin molecule shown in its unionized state. Paralytic shellfish poisoning (PSP) is one of the four recognized syndromes of shellfish poisoning, which share some common features and are primarily associated with bivalve mollusks (such as mussels, clams, oysters and scallops). These shellfish are filter feeders and accumulate neurotoxins, chiefly saxitoxin, produced by microscopic algae, such as dinoflagellates, diatoms, and cyanobacteria.[1] Dinoflagellates of the genus Alexandrium are the most numerous and widespread saxitoxin producers and are responsible for PSP blooms in subarctic, temperate, and tropical locations.[2] The majority of toxic blooms have been caused by the morphospecies Alexandrium catenella, Alexandrium tamarense, Gonyaulax catenella and Alexandrium fundyense,[3] which together comprise the A. tamarense species complex.[4] In Asia, PSP is mostly associated with the occurrence of the species Pyrodinium bahamense.[5] Also some pufferfish, including the chamaeleon puffer, contain saxitoxin, making their consumption hazardous.[6] ## Contents * 1 Pathophysiology * 2 PSP in wild marine mammals * 3 See also * 4 References * 5 External links ## Pathophysiology[edit] The toxins responsible for most shellfish poisonings are water insoluble, heat and acid-stable, and ordinary cooking methods do not eliminate the toxins. The principal toxin responsible for PSP is saxitoxin. Some shellfish can store this toxin for several weeks after a harmful algal bloom passes, but others, such as butter clams, are known to store the toxin for up to two years. Additional toxins are found, such as neosaxitoxin and gonyautoxins I to IV. All of them act primarily on the nervous system. PSP can be fatal in extreme cases, particularly in immunocompromised individuals. Children are more susceptible. PSP affects those who come into contact with the affected shellfish by ingestion.[1] Symptoms can appear ten to 30 minutes after ingestion, and include nausea, vomiting, diarrhea, abdominal pain, tingling or burning lips, gums, tongue, face, neck, arms, legs, and toes.[1] Shortness of breath, dry mouth, a choking feeling, confused or slurred speech, and loss of coordination are also possible. ## PSP in wild marine mammals[edit] PSP has been implicated as a possible cause of sea otter mortality and morbidity in Alaska, as one of its primary prey items, the butter clam (Saxidonus giganteus) bioaccumulates saxitoxin as a chemical defense mechanism.[7] In addition, ingestion of saxitoxin-containing mackerel has been implicated in the death of humpback whales.[8] Additional cases where PSP was suspected as the cause of death in Mediterranean monk seals (Monachus monachus) in the Mediterranean Sea[9] have been questioned due to lack of additional testing to rule out other causes of mortality.[10] ## See also[edit] * Amnesic shellfish poisoning * Diarrheal shellfish poisoning * Neurotoxic shellfish poisoning * Algal bloom#Harmful algal blooms (see "toxins") * Ciguatera * Cyanotoxin * Dinoflagellate#Ecology and physiology (see "neurotoxins", "red tide", and "phosphate") ## References[edit] 1. ^ a b c Clark, RF; Williams, SR; Nordt, SP; Manoguerra, AS (1999). "A review of selected seafood poisonings" (PDF). Undersea & Hyperbaric Medicine. 26 (3): 175–84. PMID 10485519. 2. ^ Taylor, F. J. R.; Fukuyo, Y.; Larsen, J.; Hallegraeff, G. M. (2003). "Taxonomy of harmful dinoflagellates". In Hallegraeff, G.M.; Anderson, D.M.; Cembella, A.D. (eds.). Manual on Harmful Marine Microalgae. pp. 389–432. ISBN 92-3-103948-2. 3. ^ Cembella, A. D. (1998). "Ecophysiology and Metabolism of Paralytic Shellfish Toxins in Marine Microalgae". In Anderson, D. M.; Cembella, A. D.; Hallegraeff, G. M. (eds.). Physiological Ecology of Harmful Algal Blooms. NATO ASI. Berlin: Springer. pp. 381–403. ISBN 978-3-662-03584-9. 4. ^ Balech, Enrique (1985). "The genus Alexandrium or Gonyaulax of the Tamarensis Group". In Anderson, Donald M.; White, Alan W.; Baden, Daniel G. (eds.). Toxic Dinoflagellates. New York: Elsevier. pp. 33–8. ISBN 978-0-444-01030-8. 5. ^ Azanza, Rhodora V.; Max Taylor, F. J. R. (2001). "Are Pyrodinium Blooms in the Southeast Asian Region Recurring and Spreading? A View at the End of the Millennium". AMBIO: A Journal of the Human Environment. 30 (6): 356–64. doi:10.1579/0044-7447-30.6.356. 6. ^ Ngy, Laymithuna; Tada, Kenji; Yu, Chun-Fai; Takatani, Tomohiro; Arakawa, Osamu (2008). "Occurrence of paralytic shellfish toxins in Cambodian Mekong pufferfish Tetraodon turgidus: Selective toxin accumulation in the skin". Toxicon. 51 (2): 280–8. doi:10.1016/j.toxicon.2007.10.002. hdl:10069/22351. PMID 17996918. 7. ^ DeGange, Anthony R.; Vacca, M. Michele (November 1989). "Sea Otter Mortality at Kodiak Island, Alaska, during Summer 1987". Journal of Mammalogy. 70 (4): 836–8. doi:10.2307/1381723. JSTOR 1381723. 8. ^ Geraci, Joseph R.; Anderson, Donald M.; Timperi, Ralph J.; St. Aubin, David J.; Early, Gregory A.; Prescott, John H.; Mayo, Charles A. (1989). "Humpback Whales (Megaptera novaeangliae) Fatally Poisoned by Dinoflagellate Toxin". Canadian Journal of Fisheries and Aquatic Sciences. 46 (11): 1895–8. doi:10.1139/f89-238. 9. ^ Hernández, Mauro; Robinson, Ian; Aguilar, Alex; González, Luis Mariano; López-Jurado, Luis Felipe; Reyero, María Isabel; Cacho, Emiliano; Franco, José; López-Rodas, Victoria; Costas, Eduardo (1998). "Did algal toxins cause monk seal mortality?". Nature. 393 (6680): 28–9. doi:10.1038/29906. hdl:10261/58748. PMID 9590687. 10. ^ Van Dolah, Frances M. (2005). "Effects of Harmful Agal Blooms". In Reynolds, John E. (ed.). Marine Mammal Research: Conservation Beyond Crisis. Baltimore, MD: Johns Hopkins University Press. pp. 85–101. ISBN 978-0-8018-8255-5. ## External links[edit] * Toxicity, Shellfish * v * t * e * Poisoning * Toxicity * Overdose History of poison Inorganic Metals Toxic metals * Beryllium * Cadmium * Lead * Mercury * Nickel * Silver * Thallium * Tin Dietary minerals * Chromium * Cobalt * Copper * Iron * Manganese * Zinc Metalloids * Arsenic Nonmetals * Sulfuric acid * Selenium * Chlorine * Fluoride Organic Phosphorus * Pesticides * Aluminium phosphide * Organophosphates Nitrogen * Cyanide * Nicotine * Nitrogen dioxide poisoning CHO * alcohol * Ethanol * Ethylene glycol * Methanol * Carbon monoxide * Oxygen * Toluene Pharmaceutical Drug overdoses Nervous * Anticholinesterase * Aspirin * Barbiturates * Benzodiazepines * Cocaine * Lithium * Opioids * Paracetamol * Tricyclic antidepressants Cardiovascular * Digoxin * Dipyridamole Vitamin poisoning * Vitamin A * Vitamin D * Vitamin E * Megavitamin-B6 syndrome Biological1 Fish / seafood * Ciguatera * Haff disease * Ichthyoallyeinotoxism * Scombroid * Shellfish poisoning * Amnesic * Diarrhetic * Neurotoxic * Paralytic Other vertebrates * amphibian venom * Batrachotoxin * Bombesin * Bufotenin * Physalaemin * birds / quail * Coturnism * snake venom * Alpha-Bungarotoxin * Ancrod * Batroxobin Arthropods * Arthropod bites and stings * bee sting / bee venom * Apamin * Melittin * scorpion venom * Charybdotoxin * spider venom * Latrotoxin / Latrodectism * Loxoscelism * tick paralysis Plants / fungi * Cinchonism * Ergotism * Lathyrism * Locoism * Mushrooms * Strychnine 1 including venoms, toxins, foodborne illnesses. * Category * Commons * WikiProject [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Paralytic shellfish poisoning	c0275144	29,895	wikipedia	https://en.wikipedia.org/wiki/Paralytic_shellfish_poisoning	2021-01-18T19:03:41	{"mesh": ["D057096"], "wikidata": ["Q2283583"]}
A rare, autosomal recessive congenital cerebellar ataxia characterized by congenital malformation of the brainstem and agenesis or hypoplasia of the cerebellar vermis leading to an abnormal respiratory pattern, nystagmus, hypotonia, ataxia, and delay in achieving motor milestones. ## Epidemiology Prevalence is estimated at approximately 1/100,000. ## Clinical description Disease onset is antenatal, although clinical presentation is typically in the neonatal period with irregular breathing pattern (episodic tachypnea and/or apnea), and nystagmus. During infancy, hypotonia may appear. Cerebellar ataxia (staggering gait and imbalance) may develop later. Delayed acquisition of motor milestones is common. Cognitive abilities are variable, ranging from severe intellectual deficit to normal intelligence. Neuro-ophthalmologic examination may show oculomotor apraxia. In some cases, seizures occur. Careful examination of the face often shows a characteristic appearance: large head, prominent forehead, high rounded eyebrows, epicanthal folds, ptosis (occasionally), an upturned nose with prominent nostrils, an open mouth (which tends to have an oval shape early on, a 'rhomboid' appearance later, and finally can appear triangular with downturned angles), tongue protrusion and rhythmic tongue motions, and occasionally low-set and tilted ears. Other features sometimes present in Joubert syndrome include retinal dystrophy, hepatopathy, nephronophthisis, and polydactyly. ## Etiology JS is due to dysfunction of the primary, non-motile cilium found in most cells. The syndrome is genetically heterogeneous with numerous genes and two loci on chromosomes 9q34 (INPP5E) and 11p12-q13 ( TMEM216) associated with the disease so far. Most of these genes encode proteins that constitute the primary cilium or the regulatory proteins and transcription factors involved in its development and function. ## Diagnostic methods Diagnosis is based on the main clinical features (hypotonia, ataxia, development delay and oculomotor apraxia), which must be accompanied by the presence of a neuroradiological hallmark, designated as the ``molar tooth sign'' (MTS) on magnetic resonance imaging (MRI). MTS results from hypoplasia of the cerebellar vermis and midbrain-hindbrain malformations. Moreover the clinical distinct sign is oculomotor apraxia. ## Differential diagnosis Differential diagnoses include Joubert syndrome-related disorders (JSRD), cerebellar vermis malformations without the MTS (which include Dandy-Walker malformation), X-linked cerebellar hypoplasia, ataxia with oculomotor apraxia types 1 and 2 (AOA1, AOA2), congenital disorders of glycosylation (CDG), 3-C syndrome, pontocerebellar hypoplasias/atrophies, orofaciodigital syndromes II and III, and Meckel-Gruber syndrome. ## Antenatal diagnosis Antenatal diagnosis is feasible through genetic testing where both disease-causing mutations have been previously identified in an affected family member. Imaging studies can suggest the disease (fetal ultrasonography and MRI) but cannot be use to conduct any antenatal diagnosis. ## Genetic counseling Transmission is autosomal recessive. Genetic counseling is recommended for families with an affected child; the recurrence risk for future offspring is 25%. ## Management and treatment Management is symptomatic and should be multidisciplinary. Education programs, physical, occupational, and speech therapy may improve the hypotonia and reduce the delay in achieving motor milestones. In general, the neurological disability and amaurosis are not progressive. Particularly relevant is the detection of nephronophthisis (NPH) which leads to chronic kidney disease which occurs in about 30% of subjects with all genetic types (with higher risk for mutations in the following genes: CEP290(12q21.32), RPGRIP1L( 16q12.2), TMEM216(11q13.1), TMEM67 (8q22.1), NPHP4 (1p36.31; 1 case), AHI1 (6q23.3)). Another aspect that may determine progressivity is the association with a liver disease, and particularly a liver fibrosis that may need liver transplantation. ## Prognosis Prognosis is favorable for moderate forms of the disease. In patients with nephronophthisis (NPH), end stage renal disease occurs in the second decade of life. Management of patients with more severe forms should be carried out by a specialized reference center. Liver disease does not recur in the transplanted liver. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Joubert syndrome	c4551568	29,896	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=475	2021-01-23T18:29:03	{"gard": ["6802"], "mesh": ["C536293"], "omim": ["213300", "610688", "612291", "614173", "614424", "614464", "614615", "614970", "615636", "616490", "616654", "616781", "616784", "617120", "617121", "617622", "617761", "618161"], "icd-10": ["Q04.3"], "synonyms": ["CPD IV", "Cerebelloparenchymal disorder IV", "Classic Joubert syndrome", "Joubert syndrome type A", "Joubert-Boltshauser syndrome", "Pure Joubert syndrome"]}
Mark Roberts, a well-known streaker, at the Hong Kong Sevens Rugby tournament in 1994. Exhibitionism is the act of exposing in a public or semi-public context those parts of one's body that are not normally exposed – for example, the breasts, genitals or buttocks. The practice may arise from a desire or compulsion to expose themselves in such a manner to groups of friends or acquaintances, or to strangers for their amusement or sexual satisfaction or to shock the bystander.[1] Exposing oneself only to an intimate partner is normally not regarded as exhibitionism. In law, the act of exhibitionism may be called indecent exposure, "exposing one's person", or other expressions. ## Contents * 1 History * 2 Psychological aspects * 3 Types of exposure * 3.1 Streaking * 3.1.1 History * 3.1.2 Definitions and etymology * 3.1.3 On college campuses * 3.1.4 In sport * 3.1.5 In popular culture * 3.1.6 Records * 4 See also * 5 References * 6 External links ## History[edit] Women "flashing", or publicly exposing their bare breasts, at Woodstock Festival Poland, 2011 Public exhibitionism by women has been recorded since classical times, often in the context of women shaming groups of men into committing, or inciting them to commit, some public action.[2] The ancient Greek historian Herodotus gives an account of exhibitionistic behaviors from the fifth century BC in The Histories. Herodotus writes that: > When people travel to Bubastis for the festival, this is what they do. Every baris carrying them there overflows with people, a huge crowd of them, men and women together. Some of the women have clappers, while some of the men have pipes which they play throughout the voyage. The rest of the men and women sing and clap their hands. When in the course of their journey they reach a community — not the city of their destination, but somewhere else — they steer the bareis close to the bank. Some of the women carry on doing what I have already described them as doing, but others shout out scornful remarks to the women in the town, or dance, or stand and pull up their clothes to expose themselves. Every riverside community receives this treatment.[3] A case of what appears to be exhibitionism in a clinical sense was recorded in a report by the Commission against Blasphemy in Venice in 1550.[4] In the UK the 4th draft of the revised Vagrancy Act of 1824 included an additional clause 'or openly and indecently exposing their persons' which gave rise to difficulties because of its ill-defined scope. During the course of a subsequent debate on the topic in Parliament, the then Home Secretary, Mr Peel, observed that 'there was not a more flagrant offence than that of indecently exposing the person which had been carried to an immense extent in the parks...wanton exposure was a very different thing from accidental exposure'.[5] The development of new technologies such as smartphones and tablets has permitted some exhibitionists to reorient their methods such as with nude selfies.[6] ## Psychological aspects[edit] Charles Lasègue was the first to use the term exhibitionist, in 1877. The term exhibitionist was first used in 1877 by French physician and psychiatrist Charles Lasègue.[7][8] Various earlier medical-forensic texts discuss genital self-exhibition, however.[9] When exhibitionistic sexual interest is acted on with a non-consenting person or interferes with a person's quality of life or normal functioning, it can be diagnosed as exhibitionistic disorder in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). The DSM states that the highest possible prevalence for exhibitionistic disorder in men is 2% to 4%. It is thought to be much less common in women.[10] In a Swedish survey, 2.1% of women and 4.1% of men admitted to becoming sexually aroused from the exposure of their genitals to a stranger.[11] A research team asked a sample of 185 exhibitionists, "How would you have preferred a person to react if you were to expose your privates to him or her?" The most common response was "Would want to have sexual intercourse" (35.1%), followed by "No reaction necessary at all" (19.5%), "To show their privates also" (15.1%), "Admiration" (14.1%), and "Any reaction" (11.9%). Only very few exhibitionists chose "Anger and disgust" (3.8%) or "Fear" (0.5%).[12] ## Types of exposure[edit] Woman flashing during Mardi Gras in New Orleans in 2008 Students mooning at Stanford University, intended as an unspecified protest and a world record attempt Various types of behavior are classified as exhibitionism,[1] including: * Anasyrma: the lifting of the skirt when not wearing underwear, to expose genitals. * Candaulism: when a person exposes his or her partner in a sexually provocative manner. * Flashing: the momentary display of bare female breasts by a woman with an up-and-down lifting of the shirt or bra or the exposure of a man's or woman's genitalia. * Martymachlia: a paraphilia which involves sexual attraction to having others watch the execution of a sexual act.[13] * Mooning: the display of bare buttocks by pulling down of trousers and underwear. The act is most often done for the sake of humour, disparagement, or mockery. * Reflectoporn: the act of stripping and taking a photograph using an object with a reflective surface as a mirror, then posting the image on the Internet in a public forum.[14] Examples include "images of naked men and women reflected in kettles, TVs, toasters and even knives and forks".[15] The instance generally credited with starting the trend involved a man selling a kettle on an Australian auction site featuring a photograph where his naked body is clearly visible;[16] other instances followed,[17][18][19] and the specific term "reflectoporn" was coined by Chris Stevens of Internet Magazine.[20] * Streaking: the act of running naked through a public place. The intent is not usually sexual but for shock value. * Sexting: the act of sending, receiving, or forwarding sexually explicit messages, photographs, or videos. * Telephone scatologia: the act of making obscene phone calls to random or known recipients. Some researchers have claimed that this is a variant of exhibitionism, even though it has no in-person physical component.[21][22] The DSM-5 diagnosis for exhibitionistic disorder has three subtypes: exhibitionists interested in exposing themselves to non-consenting adults, to prepubescent children, or to both.[10] ### Streaking[edit] For other uses, see Streaking (microbiology), Streak (disambiguation), and Streaky Bay. A streaker at the 2006 Yale–Harvard game in Cambridge, Massachusetts Streaking is the act of running nude through a public area for publicity, as a prank, a dare, or a form of protest.[23] Streaking is often associated with sporting events, but can occur in more secluded areas. Streakers are often pursued by sporting officials or the police. #### History[edit] Historical forerunners of modern-day streakers include the neo-Adamites who travelled naked through towns and villages in medieval Europe, and the 17th-century Quaker Solomon Eccles who went nude through the City of London with a burning brazier on his head.[24] At 7:00 PM on 5 July 1799, a man was arrested at the Mansion House, London, and sent to the Poultry Compter. He confirmed that he had accepted a wager of 10 guineas (equal to £1,039 today) to run naked from Cornhill to Cheapside.[25] Fines of between £10 and £50 were imposed on streakers by British and Irish magistrates in the early 1970s. The offences used for prosecution were typically minor, such as the violation of park regulations. Nevertheless, the chief law in force against streaking in England and Wales at that time remained the 16th-century vagrancy law, for which the punishment in 1550 had been whipping.[24] #### Definitions and etymology[edit] The word has been used in its modern sense only since the 1960s. Before that, to streak in English since 1768 meant "to go quickly, to rush, to run at full speed", and was a re-spelling of streek: "to go quickly" (c.1380); this in turn was originally a northern Middle English variant of stretch (c. 1250).[26] The term "streaking" was popularized by a reporter for a local Washington, D.C. news station as he watched a "mass nude run" take place at the University of Maryland in 1973. That nude run had 533 participants. As the collected mass of nude students exited Bel Air dorm, the reporter, whose voice was broadcast live over the station via a pay phone connection exclaimed... "they are streaking past me right now. It's an incredible sight!" The next day it was out on the Associated Press wire as "streaking" and had nationwide coverage.[27] #### On college campuses[edit] The examples and perspective in this section may not represent a worldwide view of the subject. You may improve this section, discuss the issue on the talk page, or create a new section, as appropriate. (May 2014) (Learn how and when to remove this template message) The first recorded incident of streaking by a college student in the United States occurred in 1804 at Washington College (now Washington and Lee University) when senior George William Crump was arrested for running naked through Lexington, Virginia, where the university is located.[28] Robert E. Lee later sanctioned streaking as a rite of passage for young Washington and Lee gentlemen. Crump was suspended for the academic session, but later went on to become a U.S. Congressman.[29] In 1973, the media reported that a "streaking epidemic" had hit Stephen F. Austin State University in Nacogdoches, Texas, with streakers being seen in residence halls, at football games and at various other on-campus locations and events, including spring graduation. The trend continued until spring 1974, when university president Ralph W. Steen—hoping to end the streaking fad—designated a day to streak the length of East College Street. The "epidemic" was covered by all of the major media outlets and became the first time streaking received concentrated national press coverage, including an article in Paris Match covering the phenomenon.[30] In December 1973, Time magazine called streaking "a growing Los Angeles-area fad" that was "catching on among college students and other groups".[31] A letter writer responded, "Let it be known that streakers have plagued the campus police at Notre Dame for the past decade", pointing out that a group of University of Notre Dame students sponsored a "Streakers' Olympics" in 1972.[32] Colleges and universities with documented traditions of campus streaking include the University of Chicago (Polar Bear run),[33] Denison University (Naked Week),[34] Oberlin College,[35] Pennsylvania State University,[36] Wellesley College,[37] and Wheaton College (the "Kingdom Run").[38] A 1967 article in the student newspaper at Carleton College described the streaking phenomenon there in negative terms, associating it with rock culture, drinking and destruction. At that time, streaking was a tradition on the Northfield, Minnesota, campus during January and February when temperatures hovered in the neighborhood of zero degrees Fahrenheit. According to The Carletonian: "Examples of [Carleton's social problems] are the large number of departing female students, the rise of class spirit, low grades, streaking, destruction, drinking, and the popularity of rock dances."[39] Dartmouth College has two streaking-related challenges: The Ledyard Challenge, in which students swim naked across the Connecticut River and run nude back across the bridge,[40] and the Blue Light Challenge, in which streaking students attempt to press the alarm on every one of the campus's blue light emergency phones.[41] As of 2005, a Thursday Night Streaking Club regularly streaks at various events and public places.[42] In 1986, the University of Michigan's Naked Mile celebrated the last day of class with a group streak across campus along an approximate one-mile path. At the height of its popularity in the late 1990s, between 500 and 800 students participated, including several hundred females. Over 1,400 students participated one year and well over one thousand during another year. However, due to enforcement of public indecency laws and pressure from administration officials concerned about increasing spectator crowds and videotaping, participation declined. By 2001, a mere 24 students participated, signaling the effective end of the Naked Mile.[43][better source needed] Students were warned by college administrators that streakers would be arrested and required to register as sex offenders for life under Megan's Law.[44][better source needed] The students at Union College held midnight "Pajama Parade" events in 1862, 1914 and several times in the 1950s. The real streaking tradition, which was nationally popular since 1973, arrived at the campus in the 1990s in the form of a nocturnal lap around the Nott Memorial known as the "Naked Nott Run."[45] To celebrate the school year's first night of heavy rainfall, a well-known tradition called "First Rain" is enacted at the University of California, Santa Cruz by students who for the entirety of the day to midnight, run around campus nearly or completely nude. Beginning at Porter, the run proceeds throughout the other colleges.[46] At the University of Vermont, a Naked Bike Ride is traditionally held at midnight at the end of each semester. Participants run, bike, unicycle, carry kayaks, push shopping carts, or pull sleds. The topic of the Naked Bike Ride has been a touchy one among UVM police, who have tried several times to do away with it. In 2011, Interim President John Bramley ended school funding for the event.[47] This resulted in the student body creating the UVM Green Caps, a group of student volunteers stationed around campus throughout the evening for the safety of students.[48][dead link] At the University of the Philippines, members of the Alpha Phi Omega fraternity streak around the campus in an annual event known as the Oblation Run.[49] The run started in 1977 to protest the banning of the movie, "Hubad na Bayani", which depicted human rights abuses in the martial law era. The event continued to occur as a protest action.[50] In 2011, the first nudist race took place at the University of Alicante (Spain).[51] #### In sport[edit] The first instance of streaking in English football took place on March 23, 1974. Prior to the start of the league match between Arsenal and Manchester City at Highbury, a middle aged man named John Taylor ran around the field. He was eventually caught by three policemen, forcibly made to wear trousers, and removed from the stadium. Taylor was fined £10 by the North London Court the next day.[52] In the sport of cricket, it is not uncommon for a male streaker to run out to the field purely for shock and entertainment value or political purposes. The first known instance of streaking in cricket took place on 22 March 1974, the first day of the third test between Australia and New Zealand at Auckland. Half an hour before the end of the day's play, while New Zealand was batting, "a dark-haired young man" ran from near the sightscreen, through mid-wicket and disappeared between the stands near the square-leg boundary. The incident occurred quickly and police did not have time to react. Reports differ on whether the man was completely naked, with some accounts stating that he may have been wearing a flesh-coloured T-shirt. On the evening of the second day, while Australian batsman Ian Redpath was on strike, an "athletic young man" was caught on television cameras running across the ground on the leg-side. The streaker ran to the men's restroom and was chased by police. When police entered the restroom, they found 20 people inside--all of whom were clothed. Authorities were unable to identify the streaker. One of the best-known instances of streaking occurred on 5 August 1975, when former Royal Navy cook Michael Angelow ran naked across Lord's during an Ashes Test. This was the first instance of streaking during a cricket match in England, and commonly mistakenly believed to be the first ever instance of streaking in cricket.[52] Another example was in the First Test of the Australia versus the I.C.C. World XI, when a rather drunken man darted out toward the field naked, shocking the Australian and World XI players, halting play until he was spear tackled to the ground by field personnel. In one notable incident in 1977, Australian test cricketer Greg Chappell spanked an invading streaker named Bruce McCauley with his cricket bat; McCauley then fell to the ground and was arrested by police.[53] The English glamour model Linsey Dawn McKenzie performed a topless streak at a televised England v. West Indies cricket match at Old Trafford in 1995. Wearing only a thong and a pair of trainers, she ran onto the field with the words "Only Teasing" written across her breasts.[54] In the 1970s, at the height of streaking's popularity, a male streaker who broke into the Augusta National golf course in Augusta, Georgia (albeit not while the Masters was in play) was shot with buckshot and slightly wounded. In 1999, a female streaker named Yvonne Robb was arrested for kissing Tiger Woods on the 18th hole at Carnoustie.[55] Play media Streaker at the West Coast Eagles vs Collingwood AFL match 2014 Streaking became popular at Australian rules football matches in the 1980s, particularly Victorian Football League Grand Finals. The trend was a trend started by Adelaide stripper Helen D'Amico at the 1982 VFL Grand Final between Carlton and Richmond, in which D'Amico streaked while wearing only a Carlton scarf.[56] At the 1988 VFL Grand Final, a fully naked woman streaked during the final quarter and was promptly arrested.[57][58] In Super Bowl XXXVIII, streaker Mark Roberts disrupted the game by running onto the field. He was eventually leveled by New England Patriots linebacker Matt Chatham, and was subsequently apprehended. Despite the worldwide audience, this event was largely unnoticed due to that game's infamous halftime show in which Janet Jackson's nude breast was revealed due to what was called a "wardrobe malfunction". Roberts would return in 2007 during the first NFL regular season game held in England between the Miami Dolphins and New York Giants, streaking during the game at Wembley Stadium.[59] In the 2006 Winter Olympics, streaker Mark Roberts interrupted the men's bronze medal curling match between the U.S. team and the UK team, wearing nothing but a strategically placed rubber chicken. For the 2008 Olympics in Beijing, officials warned visitors against streaking, amongst other forms of "bad behaviour".[60] Michael O'Brien was the first known streaker at a major sporting event when on 20 April 1974, he ran out naked onto the ground of an England vs. France rugby union match at Twickenham. The 25-year-old Australian was captured by a policeman, PC Bruce Perry, who covered his genitals with his police helmet.[61] The photograph of O'Brien under arrest became one of the most reproduced photographs of a streaker.[62] On 22 March 2009, a female streaker ran onto the pitch brandishing a green flag during the televised match between London Irish and Northampton Saints. It was in front of the season's largest crowd away from Twickenham, 21,000 fans bearing witness.[63] In a game against the Melbourne Storm at Olympic Park in 2007, a Brisbane Broncos fan streaked across the field waving his supporter jersey over his head. He was apprehended at the other side of the field to large applause.[64] During an NRL finals match between the Wests Tigers and the New Zealand Warriors at the Sydney Football Stadium on 16 September 2011, a streaker ran onto the playing field forcing the game to come to a halt as security guards attempted to apprehend the man.[65] During the final minutes of the third and deciding game of the 2013 State of Origin series, a streaker, Wati Holmwood, intruded naked upon the field, interrupting the play and possibly costing the Queensland team a try. He was tackled by security guards, escorted from the field and fined $5,500.[66] #### In popular culture[edit] The high point of streaking's pop culture significance was in 1974, when thousands of streaks took place around the world. A wide range of novelty products were produced to cash in on the fad, from buttons and patches to a wristwatch featuring a streaking Richard Nixon, to pink underwear that said "Too shy to streak."[67] The prominence of streaking in 1974 has been linked both to the sexual revolution and a conservative backlash against feminism and the campus protests of the late 1960s and early 1970s.[67] Perhaps the most widely seen streaker in history was 34-year-old Robert Opel, who streaked across the stage of The Dorothy Chandler Pavilion in Los Angeles flashing a peace sign on national US television at the 46th Academy Awards in 1974. Bemused host David Niven quipped, "Isn't it fascinating to think that probably the only laugh that man will ever get in his life is by stripping off and showing his shortcomings?" Later, evidence arose suggesting that Opel's appearance was facilitated as a publicity stunt by the show's producer Jack Haley Jr.. Robert Metzler, the show's business manager, believed that the incident had been planned in some way; during the dress rehearsal Niven had asked Metzler's wife to borrow a pen so he could write down the famous line, which was thus not the ad-lib it appeared to be.[68] Ray Stevens wrote and performed "The Streak", a novelty song about a man who is "always making the news / wearing just his tennis shoes". The song reached number one on the Billboard Hot 100 in May 1974.[69] In 2014, Russian project ChaveZZZ Reality released a single "Naked Runner" and a same-titled video-clip specifically dedicated to all streakers worldwide.[70] In Bruce Weber's 2014 account of a bike ride across America Life is a Wheel he recounts a memory of his friend Billy streaking across the campus of Clark University at the age of 18.[71] In 2019 the comic novella "Confessions of a Flash Artist" by Renald Iacovelli explored exhibitionism as an avant-garde art form. #### Records[edit] As of 2004, the record for the largest group streak was established at the University of Georgia with 1,543 simultaneous streakers on March 7, 1974.[72] ## See also[edit] * Dogging (sexual slang) * Exhibitionist narcissism * Going commando * Histrionic personality disorder * Human sexual behavior * Human sexuality * Naturism * Naked News * Nudity and sexuality * Sexualization * Sexual fetishism * Sex-positive feminism * Spring break * Sheela na gig * Toplessness * Voyeurism * Wardrobe malfunction * Human sexuality portal ## References[edit] 1. ^ a b Baunach, Dawn Michelle (2010). "Exhibitionism". Sex and Society. New York: Marshall Cavendish. p. 220. ISBN 978-0-7614-7906-2. Retrieved 22 May 2017. 2. ^ "Origin of the world". Rutgerspress.rutgers.edu. 1977-09-23. Archived from the original on 2012-11-20. Retrieved 2012-08-01. 3. ^ Herodotus. The Histories. Trans. R. Waterfield. Oxford: Oxford UP, 1998. Book Two, Chapter 60, Page 119. 4. ^ Bloch, Iwan (1914). "Fall von Exhibitionismus im 16. Jahrhundert". Zeitschrift für Sexualwissenschaft (Born): i.289. 5. ^ Rooth, F.G. (1970). "Some Historical Notes on Indecent Exposure and Exhibitionism". The Medico-Legal Journal. Part 4. 38 (4): 135–139. doi:10.1177/002581727003800405. PMID 4923872. 6. ^ Hart, Matt. "Being naked on the internet: young people’s selfies as intimate edgework." Journal of Youth Studies (2016): 1-15. 7. ^ Lasègue C. Les Exhibitionistes. L'Union Médicale (Paris), series 3, vol. 23; 1877. Pages 709–714. 8. ^ Aggrawal 2009, p. 388. sfn error: no target: CITEREFAggrawal2009 (help) 9. ^ Janssen, D.F. 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"From the Observer archive, 17 March 1974: the naked truth about streaking". The Guardian. 25. ^ The Times, 8 July 1799, "Official Appointments and Notices" 26. ^ "streak, v.2". Oxford English Dictionary (Online ed.). Oxford University Press. (Subscription or participating institution membership required.) 27. ^ Newsweek Mar 13, 1974, p. 42 col 1. Also, "Fifty years among the new words: a dictionary of neologisms", p 173 28. ^ "University Chronology". Washington and Lee University. 2011. Archived from the original on September 26, 2011. Retrieved July 1, 2011. Retrieved from Internet Archive 9 February 2014. 29. ^ "CRUMP, George William, (1786 - 1848)". Biographical Directory of the United States congress. Archived from the original on September 17, 2011. Retrieved July 1, 2011. Retrieved from Internet Archive 9 February 2014. 30. ^ Stephen F. "Student Movements: Nudes". Digital Archives and Collections – Ralph W. Steen Library. Retrieved February 9, 2014. 31. ^ "Takeoff", Time, December 10, 1973. 32. ^ "Letters", Time, December 31, 1973. 33. ^ "University of Chicago News Office \| University of Chicago Annual Polar Bear Run and Salute to the Sun to be held Friday, Jan. 18". News.uchicago.edu. 2008-01-10. Retrieved 2013-08-01. 34. ^ Ally Klein (March 3, 2008). "Attack of the naked students". media.www.denisonian.com. Archived from the original on 2011-02-25. Retrieved 2014-01-29. 35. ^ Mykyta, Myron (8 March 1974). "Streakers Here!". The Oberlin Review. Retrieved 5 Feb 2015. 36. ^ Murphy, Elizabeth (1 May 2009). "Streak raises eyebrows, keeps tradition alive". The Daily Collegian. Retrieved 15 December 2013. 37. ^ "50 Things to Do Before You Graduate". Wellesley College. Archived from the original on 2015-02-22. Retrieved 2015-02-05. 38. ^ College, Wheaton. "Perspectives From the President - Wheaton". Archived from the original on 2014-05-02. Retrieved 2014-04-30. 39. ^ John Mollenkopf (January 26, 1967). "Crash Syndrome". The Carletonian. 40. ^ "The Dartmouth Review: The Week in Review". Archived from the original on 2006-10-20. Retrieved 2009-10-16. 41. ^ "The Dartmouth - What are we talking about?". thedartmouth.com. Archived from the original on 2014-02-02. Retrieved 2014-01-29. 42. ^ Quite often during stressful final examination periods, individuals will streak through exam rooms and distribute confectionary and other sweet goods. The Dartmouth Independent: The Naked Truth Archived 2007-02-04 at the Wayback Machine 43. ^ Torin Dewey. "The History of the Naked Mile". Naked Mile. 44. ^ "Charm And Rigor — Richard Morgan". Archived from the original on 2009-07-03. Retrieved 2009-10-16. 45. ^ "About/traditions/pajama". eb.archive.org. Archived from the original on 2008-05-11. Retrieved 2014-01-29. 46. ^ Moersen, Scott (October 12, 2006). "A Naked Run Through Campus". City on a Hill Press. Retrieved April 27, 2008. 47. ^ A. John Bramley (17 November 2011). "Naked Bike Ride" (PDF). The University of Vermont. Archived from the original (PDF) on 4 May 2014. 48. ^ "Help wanted: keep NBR safe - Vermont Cynic - University of Vermont". Vermont Cynic. 2011-12-01. Retrieved 2013-08-01. 49. ^ "OBLATION RUN". 50. ^ ""Nude runners on UP campus call for Arroyo ouster"". Archived from the original on 2011-09-16. Retrieved 2009-10-16. 51. ^ INFORMACION. "En cueros por la Universidad - Informacion.es" [Nudist race at UA] (in Spanish). 52. ^ a b Sreeram, B (26 March 2017). "No, Michael Angelow was not the first streaker in Test cricket". Cricket Country. Retrieved 26 March 2017. 53. ^ "Streakers and Streaking". BBC. 2006-04-05. Retrieved 2007-08-04. 54. ^ McSmith, Andy (9 July 2007). "The Naked Truth About Streaking". The Independent. 55. ^ "Golfers on high streaker alert". BBC News. 2000-07-23. Retrieved 2010-05-24. 56. ^ Helen D'Amico Streaking.net. Retrieved from Internet Archive 6 February 2014. 57. ^ "Grand Final 1988". Demonwiki – The history of the Melbourne Football Club. Retrieved 14 February 2018. 58. ^ "VFL 1988 Grand Final - Hawks v Demons". gettyimages.com.au. Retrieved 14 February 2018. 59. ^ Benton, Dan (2007-10-29). "Streaker Mark Roberts Strikes Again; Struts His Stuff at Giants/Dolphins Game in London". Fanhouse. Archived from the original on June 23, 2007. Retrieved 2008-05-17. Retrieved from Internet Archive 12 February 2014. 60. ^ Beijing Olympics: Nudity and swearing banned, The Telegraph, 15/07/2008. Retrieved from Internet Archive 12 February 2014. 61. ^ "Britain's first streaker meets his match". The Guardian. April 22, 2006. Retrieved February 9, 2014. 62. ^ "The Twickenham Streaker". Iconic Photos. July 30, 2009. Retrieved February 12, 2014. 63. ^ "40th Anniversary of Streaking : Top 10". Canterbury. February 5, 2014. Retrieved February 12, 2014. 64. ^ "Melbourne Storm Streaker 2007". YouTube. 2007-09-09. Retrieved 2012-08-01.[unreliable source?] 65. ^ Walshaw, Nick (2011-09-16). "Fat chance of anyone other than Mr Clumsy proving the difference". The Daily Telegraph. 66. ^ "Streaker in State of Origin but it ain't over 'til the fat man sprints". The Sydney Morning Herald. July 17, 2013. Retrieved February 12, 2014. 67. ^ a b Bill Kirkpatrick (October 24, 2013). "'It Beats Rocks and Tear Gas': Streaking and Cultural Politics in the Post-Vietnam Era". Retrieved February 12, 2014. 68. ^ Steve Harvey (March 29, 1993). "What You Won't See at Oscars On Cue: Behind Those Cameras on Oscar Night". Los Angeles Times. p. F1. 69. ^ Kosser, Michael. How Nashville Became Music City U.S.A.: 50 Years of Music Row (p96), Hal Leonard Corporation; Pap/Com, 2007 ISBN 978-0634098062. 70. ^ Verichev & Cooper (music), Verichev (lyrics) (26 February 2014). ChaveZZZ Reality – Naked Runner (Music video). Sunlight Reality – via YouTube. 71. ^ Weber, Bruce (2014). Life Is a Wheel: Memoirs of a Bike-Riding Obituarist. Simon and Schuster. p. 300. ISBN 9781451695038. 72. ^ Pearson, Andy (2004-03-05). "1974: Univ. 'cracks' streaking record". The Red and Black. Archived from the original on March 8, 2011. Retrieved 2007-11-11. Retrieved from Internet Archive 6 February 2014. ## External links[edit] Wikimedia Commons has media related to Exhibitionism. * Exhibitionism explained briefly on AllPsych * Exhibitionism: the Biography by Chris Nancollas * Leah Asmelash and Jamiel Lynch (20 Aug 2019). "A man who died after falling from a hotel was trying to flee security after flashing an employee, police say" (news article). 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[Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Exhibitionism	c0015269	29,897	wikipedia	https://en.wikipedia.org/wiki/Exhibitionism	2021-01-18T19:05:01	{"mesh": ["D005084"], "umls": ["C0015269"], "wikidata": ["Q43405"]}
Progestin-induced virilization SpecialtyGynaecology, endocrinology Maternal use of androgens or high doses of certain weakly androgenic synthetic progestogens (progestins) structurally related to testosterone can masculinize (virilize) the external genitalia of a female fetus during susceptible times in pregnancy.[1][2] Some degree of fusion of the labioscrotal folds and urogenital folds and clitoral enlargement can occur if exposure occurs from the 8th through the 12th week of gestation, but only clitoral enlargement can occur if exposure occurs after the 12th week.[1][2][3][4] This can in some cases result in ambiguous genitalia.[1] Fetal masculinization of female external genitalia is usually due to enzyme abnormalities involved in adrenal steroid biosynthesis, resulting in congenital adrenal hyperplasia (CAH); fetal masculinization of female external genitalia is much less frequently due to maternal use of androgenic steroids.[3][4] Fetal masculinization of female external genitalia due to maternal use of androgenic steroids is generally less advanced than that due to CAH, and unlike CAH, does not cause progressive virilization.[5] Affected females mature normally with normal fertility, there is almost total regression of the genital anomaly in cases of simple clitoral enlargement, and in even the most severe cases, surgical correction of labioscrotal fusion is relatively simple.[5] ## Contents * 1 Dosage * 1.1 Androgens * 1.2 Progestogens * 2 History * 2.1 Androgens * 2.2 Progestogens * 2.2.1 Past use for prevention of miscarriage * 2.2.2 Past FDA labeling requirements * 3 References * 4 External links ## Dosage[edit] The incidence of fetal masculinization of female external genitalia varies with the drug and dosage.[1] ### Androgens[edit] The only sex steroid currently utilized in women that can cause virilization of female fetuses when administered in usually administered doses is the androgen danazol, a derivative of ethisterone (ethinyltestosterone).[1] Fetal masculinization of female external genitalia has resulted from doses of danazol as low as 200 mg/day, whereas 800 mg/day is the usual initial dose when danazol is used to treat severe endometriosis.[1] ### Progestogens[edit] In general, pregnane derivatives (e.g., progesterone, dydrogesterone, hydroxyprogesterone caproate, medroxyprogesterone acetate, megestrol acetate) do not virilize even in high dose; testosterone derivatives (ethisterone) and 19-nortestosterone (norethisterone, norethisterone acetate, etc.) generally virilize, but there are exceptions (e.g., noretynodrel, allylestrenol) that do not.[1] The only progestogens currently used during pregnancy (e.g., for luteal support in IVF protocols or for prevention of preterm birth in pregnant women with a history of at least one spontaneous preterm birth) are: progesterone, hydroxyprogesterone caproate, dydrogesterone, and allylestrenol.[6] Doses of 19-nortestosterones required for virilization are 10 to 20 mg/day, far in excess of those associated with inadvertent contraceptive exposure during pregnancy.[1] Genital ambiguity due to progestin exposure in pregnancy is thus mostly a topic of historical concern.[1][6] ## History[edit] ### Androgens[edit] The first drugs reported to cause fetal masculinization were the androgens methandriol and methyltestosterone in the mid-1950s.[5][7] On June 21, 1976, the FDA approved the androgen danazol (Danocrine), a derivative of ethisterone, for treatment of endometriosis, with a warning that its use in pregnancy is contraindicated because of the risk of masculinization of external genitalia of female fetuses.[8] The first case report of fetal masculinization of the external genitalia of a female infant born to a mother inadvertently treated in pregnancy with danazol was published in 1981.[9] Between 1975 and 1990, the manufacturer of Danocrine, Winthrop Laboratories, received reports worldwide of 129 pregnant women exposed to danazol, with 94 completed pregnancies and the birth of 57 female infants – 23 (40%) of whom were virilized with a pattern of clitoromegaly, fused labia and urogenital sinus formation, with genital reconstructive surgery usually, but not always, required in childhood. It is likely that the true rate of occurrence is much less than 40%, as many cases with a normal outcome would not be reported. No genital anomalies were reported where danazol therapy was discontinued before the 8th week of pregnancy.[10] The warnings against use of danazol were progressively strengthened in the 1980s. In 1991 the FDA required a black box warning that use of danazol in pregnancy is contraindicated because exposure to danazol in utero may result in androgenic effects on the female fetus causing external genitalia masculinization. The black box warning recommends a sensitive hCGβ-subunit pregnancy test immediately prior to starting danazol therapy and use of a non-hormonal method of contraception during therapy.[11][12] As of 2000, there had been published reports of fetal masculinization of female external genitalia in:[7] * 23 cases associated with danazol (all from inadvertent use from 1975–1990) * 13 cases associated with methandriol (all from use in the 1950s and 1960s) * 11 cases associated with methyltestosterone (all from use in the 1950s and 1960s) ### Progestogens[edit] #### Past use for prevention of miscarriage[edit] In the 1940s, some studies suggested that progesterone could prevent threatened abortion and might prevent habitual abortion, but oral bioavailability of progesterone is low and injections of progesterone can be painful, so orally active progestins were tried beginning with ethisterone, followed by other progestins as they became available: noretynodrel (Enovid) and norethisterone (Norlutin) in 1957, medroxyprogesterone acetate (Provera) in 1959, norethisterone acetate (Norlutate) in 1961, and dydrogesterone (Duphaston) in 1962.[13] The first case reports of fetal masculinization of external genitalia of female infants born to mothers treated in pregnancy with high-dose ethisterone and high-dose norethisterone (17α-ethinyl-19-nortestosterone) to prevent miscarriage were published in 1957 and 1958, respectively.[14][15] In a March 1960 JAMA article, pediatric endocrinologist Lawson Wilkins at Johns Hopkins reported on 34 cases of fetal masculinization of external genitalia of female infants born from 1950 to 1959 to mothers treated with high-dose (20–250 mg/day) ethisterone to prevent miscarriage, and 35 cases of fetal masculinization of external genitalia of female infants born from 1957 to 1959 to mothers treated with high-dose (10–40 mg/day) norethisterone to prevent miscarriage.[16] In 1961, Ciba and Parke-Davis added the reported association of ethisterone and norethisterone with masculinization of external genitalia of the female fetus to the precautions section of their advertisements to physicians and physician prescribing information.[17][18] A clinical trial published in the October 1962 American Journal of Obstetrics and Gynecology reported fetal masculinization of external genitalia of 14 of 59 female infants (24%) born to mothers who began high-dose (10–40 mg/day) norethisterone treatment to prevent miscarriage in the first 12 weeks of pregnancy (11 infants had slight clitoral enlargement, 1 had marked clitoral enlargement, 2 infants had marked clitoral enlargement and partial fusion of the labioscrotal folds); fetal masculinization of external genitalia of 1 of 23 female infants born to mothers who began high-dose (10–40 mg/day) norethisterone treatment to prevent miscarriage after the 12th week of pregnancy (1 infant with slight clitoral enlargement was born to a mother who began norethisterone treatment in week 13).[19] In 1964, Parke-Davis revised the physician prescribing information for Norlutin (norethisterone) and Norlutate (norethisterone acetate) to remove their indications for use in infertility, habitual abortion and threatened abortion, and add pregnancy as a contraindication to their use because of the possibility of masculinization of external genitalia of the female fetus.[20] In 1977, the FDA determined that there was no adequate evidence that progestogens (including progesterone, dydrogesterone, and 17α-hydroxyprogesterone caproate) were effective in treating threatened abortion or preventing habitual abortion and withdrew approval for those indications.[21] As of 2000, there had been published reports of fetal masculinization of female external genitalia in:[7] * 78 cases associated with ethisterone (all from use in the 1950s and early 1960s to prevent miscarriage) * 81 cases associated with norethisterone (all from use in the late 1950s and early 1960s to prevent miscarriage) #### Past FDA labeling requirements[edit] On July 22, 1977, the FDA published a notice requiring a black box warning on all progestogen drugs (except contraceptives) to warn against their use during the first four months of pregnancy because of reports of non-genital birth defects.[21][22][23][24][25][excessive citations] On January 12, 1989, after determining that progestogens did not cause non-genital birth defects, the FDA published a notice revising the black box warning on all progestogen drugs (except contraceptives) to warn against their use during the first four months of pregnancy because of past reports of genital birth defects (an increased risk of hypospadias in male fetuses and mild virilization of the external genitalia in female fetuses).[21][22][23][24][25] On November 16, 1999, the FDA published a notice effective November 16, 2000 removing (after 22 years) the black box warning on all progestogen drugs because it was unwarranted based on scientific review of current data.[21][22][23][24][25][excessive citations] ## References[edit] 1. ^ a b c d e f g h i Simpson, Joe Leigh; Kaufman, Raymond H. (1998). "Fetal effects of estrogens, progestogens and diethylstilbestrol". In Fraser, Ian S. (ed.). Estrogens and Progestogens in Clinical Practice (3rd ed.). London: Churchill Livingstone. pp. 533–53. ISBN 978-0-443-04706-0. 2. ^ a b Carson, Sandra A.; Simpson, Joe Leigh (1983). "Virilization of Female Fetuses following Maternal Ingestion of Progestational and Androgenic Steroids". In Mahesh, Virendra B.; Greenblatt, Robert B. (eds.). Hirsutism and Virilism: Pathogenesis, Diagnosis and Management. Boston: John Wright PSG Inc. pp. 177–188. ISBN 978-0-7236-7045-2. 3. ^ a b Jaffe, Robert B. (2004). "Disorders of Sexual Development". In Strauss, Jerome F.; Barbieri, Robert L. (eds.). Yen and Jaffe's Reproductive Endocrinology : Physiology, Pathophysiology, and Clinical Management (5th ed.). Philadelphia: Elsevier Saunders. pp. 464–491. ISBN 978-0-7216-9546-4. 4. ^ a b Forest, Maguelone G. (2006). "Diagnosis and Treatment of Disorders of Sexual Development". In DeGroot, Leslie J.; Jameson, J. Larry (eds.). Endocrinology (5th ed.). Philadelphia: Elsevier Saunders. pp. 2779–829. ISBN 978-0-7216-0376-6. 5. ^ a b c Schardein JL (1980). "Congenital abnormalities and hormones during pregnancy: a clinical review". Teratology. 22 (3): 251–70. doi:10.1002/tera.1420220302. PMID 7015547. 6. ^ a b Loose, Davis S.; Stancel, George M. (2006). "Estrogens and Progestins". In Brunton, Laurence L.; Lazo, John S.; Parker, Keith L. (eds.). Goodman & Gilman's The Pharmacological Basis of Therapeutics (11th ed.). New York: McGraw-Hill. pp. 1541–71. ISBN 978-0-07-142280-2. 7. ^ a b c Schardein, James L. (2000). "Hormones and Hormone Antagonists". Chemically Induced Birth Defects (3rd ed.). New York: Marcel Dekker. pp. 281–357. ISBN 978-0-8247-0265-6. 8. ^ FDA (2007). "Drug details: Danocrine NDA 017557". search: Danocrine 9. ^ Duck SC, Katayama KP (February 1981). "Danazol may cause female pseudohermaphroditism". Fertil Steril. 35 (2): 230–1. doi:10.1016/S0015-0282(16)45329-X. PMID 6781937. 10. ^ Brunskill PJ (February 1992). "The effects of fetal exposure to danazol". Br J Obstet Gynaecol. 99 (3): 212–5. doi:10.1111/j.1471-0528.1992.tb14501.x. PMID 1606119. 11. ^ Physicians' Desk Reference (46th ed.). Montvale, NJ: Medical Economics. 1992. pp. 2046–7. ISBN 978-1-56363-003-3. 12. ^ Lasser KE, Allen PD, Woolhandler SJ, Himmelstein DU, Wolfe SM, Bor DH (May 1, 2002). "Timing of new black box warnings and withdrawals for prescription medications". JAMA. 287 (17): 2215–20. doi:10.1001/jama.287.17.2215. PMID 11980521. 13. ^ Maisel, Albert Q. (1965). "Saving the Unborn". The Hormone Quest. New York: Random House. pp. 167–81. OCLC 543168. 14. ^ Gross RE, Meeker IA Jr (September 1955). "Abnormalities of sexual development; observations from 75 cases". Pediatrics. 16 (3): 303–24. PMID 13245336. 15. ^ Greenblatt RB, Jungck EC (March 22, 1958). "Delay of menstruation with norethindrone, an orally given progestational compound". JAMA. 166 (12): 1461–3. doi:10.1001/jama.1958.62990120001011. PMID 13513379. 16. ^ Wilkins L (March 5, 1960). "Masculinization of female fetus due to use of orally given progestins". JAMA. 172 (10): 1028–32. doi:10.1001/jama.1960.03020100036007. PMID 13844748. 17. ^ Jones, John Morgan (1961). Physicians' Desk Reference to Pharmaceutical Specialties and Biologicals (16th ed.). Oradell, NJ: Medical Economics. pp. 575, 750. OCLC 1644681. 18. ^ Parke-Davis (June 1961). "Introducing Norlutate...a new oral progestational agent twice as potent as Norlutin". Obstet Gynecol. 17 (6). 19. ^ Jacobson BD (October 1, 1962). "Hazards of norethindrone therapy during pregnancy". Am J Obstet Gynecol. 84 (7): 962–8. doi:10.1016/0002-9378(62)90075-3. PMID 14450719. 20. ^ Jones, John Morgan (1964). Physicians' Desk Reference to Pharmaceutical Specialties and Biologicals (19th ed.). Oradell, NJ: Medical Economics. p. 815. OCLC 1644681. 21. ^ a b c d FDA (April 3, 1999). "Progestational Drug Products for Human Use; Requirements for Labeling Directed to the Patient. Proposed Rule" (PDF). Fed Regist. 64 (70): 17985–8. 22. ^ a b c FDA (April 3, 1999). "Physician Labeling and Patient Labeling for Progestational Drug Products; Warnings and Contraindications. Notice" (PDF). Fed Regist. 64 (70): 18035–6. 23. ^ a b c FDA (November 16, 1999). "Progestational Drug Products for Human Use; Requirements for Labeling Directed to the Patient. Final Rule" (PDF). Fed Regist. 64 (220): 62110–2. 24. ^ a b c FDA (November 16, 1999). "Physician and Patient Labeling for Progestational Drug Products; Warnings and Contraindications. Notice" (PDF). Fed Regist. 64 (220): 62209. 25. ^ a b c Brent RL (2005). "Nongenital malformations following exposure to progestational drugs: the last chapter of an erroneous allegation". Birth Defects Research Part A: Clinical and Molecular Teratology. 73 (11): 906–18. doi:10.1002/bdra.20184. PMID 16206282. ## External links[edit] Classification D * ICD-10: Q52.8 * ICD-9-CM: 752.49 * v * t * e Female congenital anomalies of the genitalia, including Intersex and DSD Internal Uterine malformation * Müllerian agenesis * Cervical agenesis * Unicornuate uterus * Uterus didelphys * Bicornuate uterus * Uterine septum * Arcuate uterus Vagina * Vaginal septum * Vaginal hypoplasia * Imperforate hymen * Vaginal adenosis * Cloacal exstrophy * Vaginal atresia External * Clitoromegaly * Progestin-induced virilization * Pseudohermaphroditism * True hermaphroditism [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Progestin-induced virilization	c0342517	29,898	wikipedia	https://en.wikipedia.org/wiki/Progestin-induced_virilization	2021-01-18T18:32:33	{"umls": ["C0342517"], "wikidata": ["Q17009830"]}
With giant hemangiomas in small children, thrombocytopenia and red cell changes compatible with trauma ('microangiopathic hemolytic anemia') have been observed. The mechanism of the hematologic changes is obscure. No evidence of a simple genetic basis has been discovered. Propp and Scharfman (1966) reported a male infant with thrombocytopenia associated with a large hemangioma of the right arm and axilla. The patient had low platelet counts with a markedly diminished platelet survival time and an absence of platelet agglutinin or complement-fixing antibody. Radiochromate-tagged platelet studies suggested sequestration in the hemangioma, liver, and spleen. A combination of reticulocytosis and helmet cells was observed, possibly indicating an associated microangiopathic hemolytic anemia. The hemangioma eventually regressed with radiotherapy. David et al. (1983) reported 2 unrelated infants with thrombocytopenia and hemangiomas of the neck and left knee, respectively, both of whom were treated with corticosteroids without notable improvement. The hemangioma of the knee ultimately showed slow spontaneous resolution, but the cervical hemangioma required radiotherapy. Larsen et al. (1987) reported their 15-year experience managing 6 children with capillary hemangiomas associated with consumptive coagulopathy. In 3 of their patients, the hemangiomas remained small for many months and then suddenly enlarged, with the simultaneous appearance of a hemorrhagic diathesis. The duration of the thrombocytopenia ranged from 5 to 20 months; a variety of therapies were used. All of the patients eventually experienced resolution of their lesions and a concomitant reversal of the coagulopathy. Sencer et al. (1987) reported the case of a newborn infant with splenic hemangioendothelioma with thrombocytopenia, anemia, and disseminated intravascular coagulation who was successfully treated with splenectomy. Vellodi and Bini (1988) described a severe hyperkalemia resulting in 'malignant ventricular arrhythmias.' They attributed the hyperkalemia to breakdown of erythrocytes. Breakdown of platelets is another possible source. Enjolras et al. (1997) examined biopsy specimens from 15 patients with KMS and concluded that the vascular lesion underlying KMS is not a 'true,' classic, involuting type of hemangioma of infancy. It is a different vascular tumor with a resemblance pathologically to either tufted angioma or kaposiform hemangioendothelioma in association with lymphatic-like vessels. Enjolras et al. (1997) noted that in KMS, when cessation of platelet consumption is achieved, the tumoral mass rapidly resolves and the patient enters a biologic and clinical remission. Thus, in KMS it appears not only that the vascular anomaly triggers platelet trapping and consumption but that platelet activation inside these lesions sustains the growth of a cellular tumor component. Szlachetka (1998) reviewed the approximately 205 reported cases of KMS and discussed the pathophysiology, clinical manifestations, differential diagnosis, and treatment modalities of the disorder. Animal Model In a mouse model of Kasabach-Merritt syndrome, Verheul et al. (1999) stimulated platelet production using Peg-rHuMGDF and observed a 7- to 8-fold increase in platelet counts and a significantly increased survival, with 50% of treated animals alive at 1 month versus none of the untreated controls. There was also inhibition of tumor growth by 75%; histologic examination revealed fresh fibrin clot in the treated tumors, suggesting that higher platelet counts caused intravascular thrombosis of tumor vessels. Verheul et al. (1999) concluded that increased platelet production in this model of KMS resulted in an antivascular tumor effect via platelet trapping. Cardiac \- Hyperkalemic ventricular arrhythmia Heme \- Thrombocytopenia \- Microangiopathic hemolytic anemia Inheritance \- Autosomal dominant Lab \- Red cell changes compatible with trauma \- Hyperkalemia Skin \- Giant hemangiomas ▲ 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	HEMANGIOMA-THROMBOCYTOPENIA SYNDROME	c0221025	29,899	omim	https://www.omim.org/entry/141000	2019-09-22T16:40:23	{"mesh": ["D059885"], "omim": ["141000"], "orphanet": ["2330"], "synonyms": ["Alternative titles", "KASABACH-MERRITT SYNDROME"]}

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