Datasets:

findzebra
/

corpus

Dataset card Data Studio Files Files and versions Community

Split (1)

train · 30.7k rows

text stringlengths 297 230k	title stringlengths 4 145	cui stringlengths 4 10	idx int64 0 30.7k	source stringclasses 6 values	source_url stringlengths 33 155	retrieved_date timestamp[s]	classification_map stringlengths 2 1.45k
Bazex syndrome is a rare paraneoplastic syndrome characterized by acral psoriasiform lesions. ## Epidemiology To date, approximately 145 cases have been reported in the literature. The syndrome most commonly affects males over 40 years of age (mean age of onset: 61 years), and only 12 female patients have been reported so far. ## Clinical description Patients present with asymptomatic and symmetrical, acral, erythemato-squamous psoriasiform eruptions. The most common sites of involvement are the ears (79%), nails (75%), nose (63%), fingers (61%), hands (57%), and feet (50%). Isolated involvement of the helices of the ears is typical. Lesions may extend to the cheeks, elbows, knees and trunk. Pruritus can occur in up to 18% of cases. Histological findings are not specific and include psoriasiform epidermal hyperplasia, hyperkeratosis with parakeratosis, and perivascular lymphocytic infiltrates in the dermis. In 70% of the cases, the cutaneous lesions precede the symptoms or diagnosis of the malignancy, which is most often a squamous cell carcinoma involving the upper aerodigestive tract. ## Etiology The pathogenesis of Bazex syndrome remains unknown. It may be caused by the production of epidermal growth factor by tumor cells or by cross-reactivity between epidermal and tumor antigens. ## Diagnostic methods Diagnosis is based on clinical and histological findings. Complete evaluation of the upper aerodigestive tract should be performed to identify the underlying malignancy. ## Differential diagnosis Differential diagnoses include psoriasis, allergic contact dermatitis, photosensitivity, dermatomyositis (see this term), drug eruption, cutaneous lupus erythematosus (see this term) and mycosis. ## Management and treatment The dermatosis may respond to acitretin alone or to a combination of acitretin and UVA phototherapy. Cutaneous lesions regress with the treatment of the underlying malignancy, whereas nail lesions may persist. Recurrence of skin lesions in a successfully treated patient implies a recurrence of the malignancy. ## Prognosis Prognosis is related to the underlying neoplasm. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Bazex syndrome	c0346104	25,000	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=166113	2021-01-23T19:07:19	{"mesh": ["C537663"], "umls": ["C0346104", "C0406355"], "synonyms": ["Acrokeratosis of Bazex", "Acrokeratosis paraneoplastica", "Acrokeratosis paraneoplastica of Bazex"]}
Tetrasomy 18p is a very rare structural chromosomal anomaly affecting multiple body systems and characterized clinically by craniofacial abnormalities, delayed development, cognitive impairment, changes in muscle tone, distinctive facial features, and rarely renal malformations. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Tetrasomy 18p	c0795868	25,001	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3307	2021-01-23T17:42:20	{"gard": ["35"], "mesh": ["C538306"], "omim": ["614290"], "umls": ["C0795868"], "icd-10": ["Q99.8"], "synonyms": ["Isochromosome 18p"]}
X-linked spondyloepiphyseal dysplasia tarda is an inherited skeletal disorder that affects males only. Physical characteristics include moderate short-stature (dwarfism); moderate to severe spinal deformities; barrel-chest; disproportionately short trunk and neck; disproportionately long arms, and premature osteoarthritis, especially in the hip joints. Final male adult height ranges from 4 feet 10 inches to 5 feet 6 inches. Other skeletal features of this condition include decreased mobility of the elbow and hip joints, arthritis, and abnormalities of the hip joint which causes the upper leg bones to turn inward. This condition is caused by mutations in the TRAPPC2 gene and is inherited in an X-linked recessive pattern. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Spondyloepiphyseal dysplasia tarda X-linked	c3541456	25,002	gard	https://rarediseases.info.nih.gov/diseases/4985/spondyloepiphyseal-dysplasia-tarda-x-linked	2021-01-18T17:57:32	{"mesh": ["D010009"], "omim": ["313400"], "umls": ["C0220776"], "synonyms": ["SED", "X linked spondyloepiphyseal dysplasia tarda", "X-linked spondyloepiphyseal dysplasia"]}
## Summary ### Clinical characteristics. Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) is characterized by inappropriately low serum concentrations of the gonadotropins LH (luteinizing hormone) and FSH (follicle-stimulating hormone) in the presence of low circulating concentrations of sex steroids. IGD is associated with a normal sense of smell (normosmic IGD) in approximately 40% of affected individuals and an impaired sense of smell (Kallmann syndrome) in approximately 60%. IGD can first become apparent in infancy, adolescence, or adulthood. Infant boys with congenital IGD often have micropenis and cryptorchidism. Adolescents and adults with IGD have clinical evidence of hypogonadism and incomplete sexual maturation on physical examination. Adult males with IGD tend to have prepubertal testicular volume (i.e., <4 mL), absence of secondary sexual features (e.g., facial and axillary hair growth, deepening of the voice), decreased muscle mass, diminished libido, erectile dysfunction, and infertility. Adult females have little or no breast development and primary amenorrhea. Although skeletal maturation is delayed, the rate of linear growth is usually normal except for the absence of a distinct pubertal growth spurt. ### Diagnosis/testing. IGD is typically diagnosed in adolescents presenting with absent or partial puberty using biochemical testing that reveals low serum testosterone or estradiol (hypogonadism) that results from complete or partial absence of GnRH-mediated release of LH and FSH (hypogonadotropic hypogonadism [HH]) in the setting of otherwise normal anterior pituitary anatomy and function and in the absence of secondary causes of HH. Pathogenic variants in more than 25 genes account for about half of all IGD; the genetic cause for the remaining cases of IGD is unknown. ### Management. Treatment of manifestations: To induce and maintain secondary sex characteristics, gradually increasing doses of testosterone or human chorionic gonadotropin (hCG) injections in males or estrogen and progestin in females; to stimulate spermatogenesis or folliculogenesis, either combined gonadotropin therapy (hCG and human menopausal gonadotropins [hMG] or recombinant FSH) or pulsatile GnRH therapy. If conception fails despite spermatogenesis in a male or ovulation induction in a female, in vitro fertilization may be an option. Prevention of secondary complications: Optimal calcium and vitamin D intake should be encouraged and specific treatment for decreased bone mass as needed. Surveillance: For children of both sexes with findings suggestive of IGD, monitor at regular intervals after age 11 years: sexual maturation (by Tanner staging on physical examination); gonadotropin and sex hormone levels; bone age. In individuals with confirmed IGD, monitor at regular intervals: serum sex steroid levels (to guide optimal hormone replacement); bone mineral density. Evaluation of relatives at risk: If the pathogenic variant(s) in a family are known, genetic testing of prepubertal at-risk relatives may be indicated to clarify their genetic status. Because of variable expressivity, a prepubertal child with a known pathogenic variant may progress through puberty in a normal or delayed fashion, or not at all; therefore, clinical reevaluation over time is necessary. ### Genetic counseling. IGD can be inherited in an X-linked, autosomal dominant, or autosomal recessive manner. Almost all IGD-related genes have also been associated with indeterminate or oligogenic inheritance. Recurrence risk counseling is based on family history and the results of molecular genetic testing when available. Carrier testing for at-risk relatives in families with X-linked IGD or autosomal recessive IGD is possible if the pathogenic variant(s) in the family are known. Prenatal testing for pregnancies at increased risk is possible if the pathogenic variant(s) in the family are known. ## Diagnosis Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) can be associated with a normal sense of smell (normosmic IGD) or an impaired sense of smell (Kallmann syndrome [KS]). ### Suggestive Findings Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) should be suspected in individuals with the following: * Absent or partial puberty at presentation in adolescents; low serum testosterone or estradiol on biochemical testing * Findings of incomplete sexual maturation on physical examination as determined by Tanner staging (see Table 1): * Men with IGD typically have Tanner stage I-II genitalia (prepubertal testicular volumes; i.e., <4 mL); however, some males show evidence of partial pubertal maturation [Pitteloud et al 2001]. * Women with IGD typically have Tanner stage I breast development and amenorrhea; however, some have spontaneous breast development and occasional menses [Shaw et al 2011]. * Both men and women with IGD typically have Tanner stage II-III pubic hair, since pubic hair is controlled in part by adrenal androgens. In rare males, IGD may present later in adulthood (i.e., adult-onset IGD). However, in these patients, as puberty was not disrupted, sexual maturation is complete and secondary sexual characteristics may be fully developed. Diagnosis of adult-onset IGD relies on documentation of hypogonadotropic hypogonadism (HH) and absence of other secondary causes of HH. * Laboratory findings of IGD (see Figure 1 and Figure 2 for algorithm) * Total testosterone (T) <100 ng/dL in males and estradiol (E2) <50 pg/mL in females * Inappropriately low or normal serum concentration of LH (luteinizing hormone) and FSH (follicle stimulating hormone) in the presence of low circulating concentrations of sex steroids. Levels of other anterior pituitary hormones are typically normal. * Imaging findings of IGD * In persons with IGD: typically, normal-appearing hypothalamus and pituitary on MRI exam * In persons with KS: typically, aplasia or hypoplasia of the olfactory bulbs/sulci/tracts. * Olfactory findings. Olfactory function is evaluated by history and by formal diagnostic smell tests, such as the University of Pennsylvania smell identification test (UPSIT), a "scratch and sniff" test that evaluates an individual's ability to identify 40 microencapsulated odorants and can be easily performed in most clinical settings [Doty 2007]. Anosmia, hyposmia, or normosmia is identified using the UPSIT manual normogram, which incorporates an individual’s score, age at testing, and gender. Individuals with IGD with either self-reported complete anosmia or a score of hyposmia/anosmia on UPSIT testing are diagnosed with KS, while those with normal olfactory function are diagnosed with normosmic IGD (nIGD) [Lewkowitz-Shpuntoff et al 2012]. #### Figure 1. Testing algorithm to establish the diagnosis of isolated GnRH deficiency (IGD) in males #### Figure 2. Testing algorithm to establish the diagnosis of isolated GnRH deficiency (IGD) in females ### Table 1. Tanner Staging View in own window StageNormal Findings Pubic HairMale GenitaliaFemale Breast Development INoneChildhood appearance of testes, scrotum, and penis (testicular volume <4 mL)No breast bud, small areola, slight elevation of papilla IISparse hair that is long and slightly pigmentedEnlargement of testes; reddish discoloration of scrotumFormation of the breast bud; areolar enlargement IIIDarker, coarser, curly hairContinued growth of testes and elongation of penisContinued growth of the breast bud and areola; areola confluent with breast IVAdult hair covering pubisContinued growth of testes, widening of the penis with growth of the glans penis; scrotal darkeningContinued growth; areola and papilla form secondary mound projecting above breast contour VLaterally distributed adult-type hairMature adult genitalia (testicular volume >15 mL)Mature (areola again confluent with breast contour; only papilla projects) ### Establishing the Diagnosis The diagnosis of IGD is established in a proband based on clinical and biochemical investigations above; a genetic diagnosis can be made with identification of pathogenic variant(s) in one of the genes listed in Table 2a and Table 2b. See Table 2a for the most common genetic causes (i.e., pathogenic variants of any one of the genes included in this table account for >2% of IGD) and Table 2b for less common genetic causes (i.e., pathogenic variants of any one of the genes included in this table are reported in only a few families). Molecular testing approaches can include serial single-gene testing, use of a multigene panel, and more comprehensive genomic testing. Serial single-gene testing can be considered based on mode of inheritance and clinical findings, especially non-reproductive phenotypic features that indicate that pathogenic variation of a particular gene is most likely. Sequence analysis of the gene of interest is performed first, followed by gene-targeted deletion/duplication analysis if no pathogenic variant is found. To help prioritize the order of serial single-gene testing, the following can be considered (see Figure 3 and Figure 4): #### Figure 3. Genes associated with isolated GnRH deficiency (IGD) by sense of smell and mode of inheritance #### Figure 4. Suggested guidelines for prioritization of genetic testing for persons with IGD based on phenotype [modified from Au et al 2011] * Sense of smell * Pathogenic variants in CHD7, FGF8, FGF17, FGFR1, HS6ST1, NSMF (NELF), PROK2, PROKR2, and WDR11 cause both Kallmann syndrome (KS) and normosmic IGD (nIGD). * Pathogenic variants in ANOS1 (KAL1), CCDC141, FEZF1, IL17RD, SEMA3A, SEMA3E, and SOX10 cause KS. * Pathogenic variants in GNRH1, GNRHR, KISS1, KISS1R (GPR54), TAC3, and TACR3 cause nIGD. * Mode of inheritance * X-linked. Sequence analysis of ANOS1 (KAL1) is the highest-yield molecular genetic test. * Autosomal dominant. In families with clear autosomal dominant inheritance, testing of CHD7, FGFR1, FGF8 and SOX10 can be considered. * Autosomal recessive. Testing of GNRH1, GNRHR, KISS1, KISS1R, TAC3, and TACR3 can be considered in families with autosomal recessive normosmic IGD; testing of FEZF1, PROK2 and PROKR2 can be considered in families with autosomal recessive KS. * Associated phenotypic features. The presence of some associated clinical phenotypic features may also help prioritize genetic testing in IGD [Costa-Barbosa et al 2013]. See Figure 4. A multigene panel that includes the genes listed in Table 2a and Table 2b and other genes of interest (see Differential Diagnosis) may be considered. This should be the first step when the proband has no clearly affected family members and/or no associated phenotypic features. Note: 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 and genome sequencing may be considered. Such testing may provide or suggest a diagnosis not previously considered (e.g., mutation of a different gene or genes that results in a similar clinical presentation). For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. ### Table 2a. Molecular Genetic Testing Used in Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency: Most Common Genetic Causes View in own window Gene 1, 2% of IGD Attributed to Pathogenic Variants in This Gene 3Proportion of Pathogenic Variants 4 Detected by Test Method Sequence analysis 5Gene-targeted deletion/duplication analysis 6 ANOS1 (KAL1)5%-10% (KS)~88%-99%≤12% in one study (4/33 persons w/KS) 7 CHD75%-10% (KS or nIGD)~100%Unknown 8 FGFR1~10% (KS or nIGD)~99%Rare 9 GNRHR5%-10% (nIGD)~100%Unknown 8 IL17RD2%-5% (KS or nIGD)~100%Unknown 8 PROKR2~5% (KS or nIGD)~100%Unknown8 SOX102%-5% (KS)~100%Unknown 8 TACR3~5% (nIGD)~100%Unknown 8 Pathogenic variants of any one of the genes included in this table account for >2% of IGD. KS = Kallmann syndrome; nIGD = normosmic isolated gonadotropin-releasing hormone deficiency 1\. Genes are listed in alphabetic order. 2\. See Table A. Genes and Databases for chromosome locus and protein. 3\. Proportion of IGD attributed to these genes is determined from the author’s cohort of 950 probands with IGD who were screened for rare sequence variants (<1% of control cohort). 4\. See Molecular Genetics for information on pathogenic allelic variants detected. 5\. 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. 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\. 12% of persons with KS harbored intragenic deletions in ANOS1 [Pedersen-White et al 2008]. 8\. No data on detection rate of gene-targeted deletion/duplication analysis are available. 9\. FGFR1 deletions are rare [Trarbach et al 2010b]. ### Table 2b. Molecular Genetics of Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency: Less Common Genetic Causes View in own window Gene 1, 2, 3CommentsReference AXLDescribed in 1 report: 4/104 persons w/KS or nIGDSalian-Mehta et al [2014] CCDC141Described in 1 report: 1/20 persons w/KSHutchins et al [2016] DUSP6Described in 1 report: 5/386 persons w/KS or nIGDMiraoui et al [2013] FEZF1Described in 1 report: 2/30 persons w/KSKotan et al [2014] FGF8<2% 4 of persons w/KS or nIGD FGF17Described in 1 report: 3/386 persons w/KS or nIGDMiraoui et al [2013] FLRT3Described in 1 report: 3/386 persons w/KS or nIGDMiraoui et al [2013] GNRH1Typically AR; <2% 4 of persons w/nIGD HS6ST1<2% of persons w/KS or nIGD 4, 5 KISS1Typically AR; <2% of persons w/nIGD 4 KISS1RTypically AR; <2% of persons w/nIGD 4 POLR3BDescribed in 1 report: 3/565 persons w/KS or nIGDRichards et al [2017] PROK2Typically AR; <2% 4 of persons w/KS or nIGD 4 SEMA3A<2% of persons w/KS or nIGD 4, 5 SEMA3EDescribed in 1 report: 1/121 persons w/KS or nIGDCariboni et al [2015] SPRY4Described in 1 report: 14/386 persons w/KS or nIGDMiraoui et al [2013] SRA1Described in 1 report: 3/136 persons w/nIGDKotan et al [2016] TAC3Typically AR; <2% of persons w/nIGD 4 WDR11Described in 1 report: 1 person w/balanced translocation; 6/201 persons w/KS or nIGDKim et al [2010] Pathogenic variants of any one of the genes listed in this table are reported in only a few families (i.e., <2% of IGD) AR = autosomal recessive; KS = Kallmann syndrome; nIGD = normosmic isolated gonadotropin-releasing hormone deficiency 1\. Genes are listed in alphabetic order. 2\. See Table A. Genes and Databases for chromosome locus and protein. 3\. Genes are not described in detail in Molecular Genetics but may be included here (pdf). 4\. Proportion of IGD attributed to these genes is determined from the author’s cohort of 950 probands with IGD who were screened for rare sequence variants (<1% of control cohort). 5\. Pathogenic variants in this gene are not thought to cause IGD without contributions from other IGD-related genes; thus, the proportion of IGD caused by pathogenic variants in this gene is unknown. ## Clinical Characteristics ### Clinical Description The clinical manifestations of isolated GnRH deficiency (IGD) depend on the stage of development at which the deficiency in the reproductive axis first occurred – in infancy, adolescence, or (rarely) adulthood. Most individuals with IGD are identified at puberty; however, suggestive clinical features may be present in infancy. #### Reproductive Phenotype Infancy. Microphallus (stretched penile length <1.9 cm in a full-term newborn male) and cryptorchidism (undescended testes) represent two early clinical findings that may be present in male infants with IGD, although the significance of these findings is usually not recognized until puberty. Both clinical features reflect congenital GnRH deficiency and, if measured in male infants, concentrations of testosterone, LH (luteinizing hormone), and FSH (follicle stimulating hormone) are low in the first six months of life in these infants (neonatal window) [Grumbach 2005]. Although microphallus and cryptorchidism can occur in both forms of IGD (KS and normosmic IGD), these features are more common in males with KS than in those with normosmic IGD [Pitteloud et al 2002a]. Female infants typically do not exhibit any clinical features that may indicate IGD. Adolescence. At puberty, most individuals with IGD have abnormal sexual maturation, usually with incomplete development of secondary sexual characteristics. However, the degree to which sexual maturation is affected can vary (see Fertile hypogonadal variant of IGD in males). Males with IGD typically have prepubertal testicular volume (i.e., <4 mL), absence of secondary sexual features (e.g., facial and axillary hair growth and deepening of the voice), and decreased muscle mass. Females with IGD typically have little or no breast development and primary amenorrhea, but milder presentations with spontaneous menses are recognized [Shaw et al 2011]. Since adrenal maturation proceeds normally, the low levels of androgens produced in the adrenal glands may be sufficient for normal onset of pubic hair growth (adrenarche) in both sexes. Because of the failure of growth plates in the bone to fuse in the absence of sex hormones, most individuals with IGD, both males and females may have disproportionate arm span compared to height (arm span typically exceeds height by ≥5 cm). Whereas skeletal maturation is delayed, the rate of linear growth is usually normal (save for the absence of a distinct pubertal growth spurt) [Van Dop et al 1987]. Fertile hypogonadal variant of IGD in males. Some degree of pubertal development can occur in some individuals with IGD. The relatively mildest form of abnormal pubertal development is found in males who have clinical evidence of hypogonadism with low serum concentration of testosterone but evidence of partial pubertal development with normal or near-normal testicular volumes, normal levels of inhibin B (the seminiferous tubular secretory protein), and, often, sperm in their ejaculate. Reversal of IGD, defined as restoration of normal serum testosterone concentrations after cessation of even brief treatment with sex steroid, gonadotropin, or GnRH, occurs in about 10% of all men with IGD, including those with KS [Raivio et al 2007, Sidhoum et al 2014]. This post-treatment “awakening” of the hypothalamo-pituitary-gonadal (HPG) axis suggests the presence of hypothalamic GnRH neurons that do not function during adolescence and possibly require hitherto undefined stimuli (potentially environmental/sex steroid exposure) to initiate normal activity. The precise physiologic basis of the reversal phenomenon is yet to be fully understood. #### Olfactory Phenotype Anosmia. The impaired olfactory function in Kallmann syndrome can be either hyposmia or complete anosmia) [Bianco & Kaiser 2009]. The difference between hyposmia and anosmia is quantitative and not qualitative (i.e., odorants can be variably affected in persons with hyposmia). Most individuals with impaired smell do not have any physical or social impairment and the finding often goes unnoticed until IGD is diagnosed. #### Reproductive and Non-Reproductive Phenotypes by Gene Table 3 summarizes by gene the scope of the reproductive defect, olfactory function, and non-reproductive issues. ### Table 3. Isolated GnRH Deficiency (IGD) Phenotype by Gene View in own window GenePhenotypic FeaturesReferences ReproductiveOlfactoryOther Non-Reproductive ANOS1 (KAL1) 1, 2IGD (males)Anosmia or hyposmia * Digital synkinesia (in ~80% males) * Unilateral renal agenesis (in ~30% males) 3 * High-arched palate Oliveira et al [2001], Quinton et al [2001], Pitteloud et al [2002a], Massin et al [2003], Costa-Barbosa et al [2013] AXL 2, 4IGD to normal puberty 4Anosmia or normosmia 4NoneSalian-Mehta et al [2014] CCDC141IGDAnosmiaNoneHutchins et al [2016] CHD7 1, 2IGD to normal puberty 4Anosmia or normosmia 4 * High-arched or cleft palate * Dental agenesis * Auricular dysplasia * Perceptive deafness & hypoplasia of semicircular canals * Coloboma * Short stature * Intellectual disability Kim et al [2008], Jongmans et al [2009], Costa-Barbosa et al [2013] DUSP6 2, 4IGD to normal puberty 4Anosmia or normosmia 4NoneMiraoui et al [2013] FEZF1 1IGDAnosmiaNoneKotan et al [2014] FGF8 1, 2, 4IGD to normal puberty 4Anosmia or normosmia 4 * Cleft lip and/or palate * Hearing loss * Ocular hypertelorism * Hyperlaxity of the digits * Camptodactyly Falardeau et al [2008], Trarbach et al [2010a] FGF17 2, 4IGD to normal puberty 4Anosmia or normosmia 4NoneMiraoui et al [2013] FGFR1 1, 2Complete IGD to normal puberty IGD in males > femalesAnosmia or normosmia 4 * Synkinesia (in ~10%) * Cleft lip and/or palate * Agenesis of 1+ teeth * Digit malformations (brachydactyly, syndactyly) Dodé et al [2003], Pitteloud et al [2006b], Costa-Barbosa et al [2013] FLRT3 2, 4IGD to normal puberty 4Anosmia or normosmia 4NoneMiraoui et al [2013] GNRH1 1, 2IGD (recessive); IGD to normal puberty 4 (heterozygous pathogenic variants)NormosmiaNoneBouligand et al [2009], Chan et al [2009] GNRHR 1, 2IGD (recessive); IGD to normal puberty 4 (heterozygous pathogenic variants)NormosmiaNonede Roux et al [1997] Cerrato et al [2006], Bédécarrats & Kaiser [2007] HS6ST1 2, 4IGD to normal puberty 4Anosmia or normosmia 4NoneTornberg et al [2011] IL17RD 1, 2, 4IGD to normal puberty 4AnosmiaHearing lossMiraoui et al [2013] KISS1 1, 2IGD (recessive); IGD to normal puberty 4 (heterozygous pathogenic variants)NormosmiaNoneTopaloglu et al [2012] KISS1R 1, 2IGD (recessive); IGD to normal puberty 4 (heterozygous pathogenic variants)NormosmiaNonede Roux et al [2003], Seminara et al [2003], Semple et al [2005] NSMF 2IGD to normal puberty 4Anosmia or normosmia 4NoneXu et al [2011] POLR3BIGD (recessive)NormosmiaNoneRichards et al [2017] PROKR2 1, 2, 4 and PROK2 1, 2, 4IGD (recessive); IGD to normal puberty 4 (heterozygous pathogenic variants)Anosmia or normosmia 4NoneCosta-Barbosa et al [2013] SEMA3A 2, 4IGD to normal puberty 4Anosmia or hyposmiaNoneCariboni et al [2011], Hanchate et al [2012] SEMA3E 2, 4IGDAnosmiaNoneCariboni et al [2015] SOX10 1IGDAnosmia * Hearing loss * Iris hypopigmentation Pingault et al [2013], Suzuki et al [2015] SPRY4 2, 4IGD to normal puberty 4Anosmia or normosmia 4NoneMiraoui et al [2013] SRA1IGDNormosmiaNoneKotan et al [2016] TAC3 1, 2, 4IGD (recessive); IGD to normal puberty 4 (heterozygous pathogenic variants)NormosmiaNoneTopaloglu et al [2009] TACR3 1, 2, 4IGD (recessive); IGD to normal puberty 4 (heterozygous pathogenic variants)NormosmiaNoneGuran et al [2009], Topaloglu et al [2009], Gianetti et al [2010] WDR11 2, 4IGD to normal puberty 4Anosmia or normosmia 4NoneKim et al [2010] 1\. Monogenic inheritance 2\. Oligogenic inheritance 3\. Often asymptomatic; also reported in KS of unknown cause 4\. Depending on penetrance, especially in the heterozygous state ### Pathophysiology Pulsatile secretion of GnRH into the hypophyseal portal circulation represents the initial neuroendocrine step in the regulation of the hypothalamo-pituitary-gonadal (HPG) axis in both sexes. Thus, this specialized GnRH neuronal network plays a commanding role in this biologic hierarchy and controls episodic gonadotropin secretion, modulates gonadal steroid feedback, and ultimately determines the initiation or suppression of pubertal development and fertility across the life cycle [Hoffman & Crowley 1982, Crowley et al 1985]. Under normal conditions, the GnRH neuronal network undergoes a series of dynamic changes from fetal life to adulthood. The initiation of GnRH secretion is initiated in early fetal life and remains active until the first several months of infancy (representing the "mini-puberty"), and then becomes remarkably dampened during the years of the childhood "quiescence" [Waldhauser et al 1981]. At puberty, unknown biologic triggers re-ignite GnRH secretion, resulting in full sexual maturation. Therefore, the controls of the reproductive axis are in dynamic flux, turning on and turning off in response to as-yet-unknown biologic signals at various points in the reproductive life cycle. In individuals with IGD, analyses of the pulsatile pattern of gonadotropins have demonstrated a rather broad spectrum of abnormal developmental patterns varying from completely absent GnRH-induced LH pulses to sleep-entrained GnRH release that is indistinguishable from that of early puberty [Spratt et al 1987, Nachtigall et al 1997, Raivio et al 2007]. This broad spectrum of neuroendocrine activity accounts for the variable reproductive phenotypes observed in persons with IGD. ### Genotype-Phenotype Correlations Gene-specific phenotypes have been noted; see Table 3 and Figure 4. No reproductive or non-reproductive phenotype is specific to a single pathogenic variant or particular type of pathogenic variant in any of the IGD-related genes. ### Penetrance The underlying genetic etiology typically determines the penetrance of both reproductive and non-reproductive phenotypes. The penetrance for the KS phenotype (both IGD and anosmia) is generally complete in males with an ANOS1 (KAL1) pathogenic variant. However, other non-reproductive phenotypes may have variable penetrance even in the setting of the same ANOS1 (KAL1) defect. One set of identical twin males with a small deletion in ANOS1 (KAL1) with discordant neuroendocrine and non-reproductive phenotypes has been documented: one twin had a ventricular septal defect and a much greater LH and FSH response to a serial LH-RH stimulation test, whereas the other had exotropia and a lower response to the serial LH-RH stimulation test [Matsuo et al 2000]. Penetrance for IGD is also fairly high when pathogenic variants occur in the biallelic state (i.e., recessive variants) (FEZF1, GNRH1, GNRHR, IL17RD, KISS1, KISS1R, TAC3, TACR3). However, penetrance for the reproductive phenotype in those with pathogenic heterozygous variants in almost all known IGD-related genes is incomplete as individuals with normal gonadal function who are heterozygous for pathogenic variants in these genes have been documented. Discordance for KS has also been demonstrated in identical twins, suggesting that additional modifiers may play a role in phenotypic expression [Hipkin et al 1990]. Penetrance for anosmia in men with an ANOS1 (KAL1) pathogenic variant is generally complete, whereas penetrance for abnormal olfactory function in individuals with IGD and heterozygous pathogenic variants in several genes (CHD7, FGFR1, FGF8, FGF17, HS6ST1, NSMF, PROK2, PROKR2) is incomplete as normosmia, hyposmia, or anosmia can be seen [Pitteloud et al 2006a, Cole et al 2008, Falardeau et al 2008, Miraoui et al 2013, Balasubramanian et al 2014]. ### Nomenclature The biochemical term "hypogonadotropic hypogonadism" has evolved with the increased understanding of reproductive physiology. The term “hypogonadism” refers to impaired sexual development based on findings from the individual’s clinical history (e.g., amenorrhea, hot flashes, erectile dysfunction) as well as physical examination (e.g., small testes, vaginal pallor). With greater understanding of the hypothalamo-pituitary-gonadal (HPG) axis (see Pathophysiology) and the introduction of urinary gonadotropin measurements, the term "hypergonadotropic" hypogonadism was used to identify those with a primary gonadal defect, while "hypogonadotropic" hypogonadism identified those with a central (i.e., pituitary or hypothalamic) defect. When anatomic (and later functional) causes of central hypogonadism were identified, "idiopathic" or "isolated" hypogonadotropic hypogonadism (IHH) came into use to indicate those individuals in whom secondary causes of hypogonadotropic hypogonadism had been excluded. Subsequently the ability to measure the effect of exogenous GnRH administration demonstrated that the vast majority of individuals with "idiopathic" HH had a functional deficiency of GnRH resulting from a defect in GnRH biosynthesis, secretion, and/or action (hence "isolated GnRH deficiency" [IGD]). Aside from hypothalamic GnRH deficiency, individuals with IGD typically have normal pituitary function tests and their hypogonadism typically responds to a physiologic regimen of exogenous GnRH [Hoffman & Crowley 1982]. At this point, the term "isolated GnRH deficiency" (IGD) more properly reflects the current understanding of the clinical entity rather than the previous biochemical description of IHH and, thus, is the better term for what was previously called IHH. ### Prevalence A recent epidemiologic study in Finland showed a minimal incidence of KS of 1:30,000 in males and 1:125,000 in females [Laitinen et al 2011]. In the authors’ cohort of 250 individuals with IGD, males predominate with a male-to-female ratio of nearly 4:1 [Seminara et al 1998]. KS accounts for nearly two thirds of individuals with isolated GnRH deficiency (IGD). ## Differential Diagnosis Other Causes of Hypogonadotropic Hypogonadism Hypogonadotropic hypogonadism refers to a diverse group of clinical conditions with characteristic biochemical findings of inappropriately low serum concentrations of LH (luteinizing hormone) and FSH (follicle stimulating hormone) occurring in the setting of hypogonadism. Distinguishing between isolated GnRH deficiency (IGD) and secondary causes of hypogonadotropic hypogonadism and syndromic/genetic causes of hypogonadotropic hypogonadism often requires additional clinical, laboratory, and radiologic evaluations. These may include physical examination for other systemic findings, family history, and measurement of serum concentration of other pituitary hormones, serum iron studies, and hypothalamic/pituitary imaging. Of note, despite a thorough evaluation, IGD can sometimes be difficult to distinguish from other causes of decreased gonadotropin secretion. Hence, molecular genetic testing of the known IGD-related genes (Table 2) may help make the diagnosis of IGD Acquired causes. Multiple disease processes ranging from systemic diseases to brain and pituitary tumors can result in impaired gonadotropin secretion. These conditions, which can be relatively common and frequently give rise to defects in other pituitary hormones, include the following: * CNS or pituitary tumors * Pituitary apoplexy * Brain/pituitary radiation * Head trauma * Drugs: GnRH agonists/antagonists, glucocorticoids, narcotics, chemotherapy, drugs causing hyperprolactinemia * Functional deficiency resulting from hyperprolactinemia, chronic systemic illness, eating disorders, malnutrition, hypothyroidism, diabetes mellitus, Cushing’s disease * Systemic diseases such as sarcoidosis and histiocytosis Syndromes listed in Table 4 can be associated with hypogonadotropic hypogonadism along with other significant clinical findings and/or other pituitary hormone deficits. ### Table 4. Syndromes Associated with Hypogonadotropic Hypogonadism View in own window SyndromeGenetic Mechanism / Associated GenePhenotypeReference Bardet-Biedl syndromePathogenic variants in of one of 19 genes 1Developmental delay, visual impairment, postaxial polydactyly, obesity, renal impairment CHARGE syndromeCHD7Coloboma, heart defect, choanal atresia, growth retardation, ear abnormalitiesPinto et al [2005], Lalani & Belmont [2009] Combined pituitary hormone deficiencyHESX1Various degrees of hypopituitarismPROP1-Related Combined Pituitary Hormone Deficiency, Combined Pituitary Hormone Deficiencies LHX3 LHX4 POU1F1 PROP1 Gordon-Holmes syndromeOTUD4 PNPLA6 RNF216 STUB1Cerebellar ataxia, dementiaSeminara et al [2002], Margolin et al [2013] HFE-associated hereditary hemochromatosisHFECirrhosis, diabetes, cardiomyopathy, arthritis, skin hyperpigmentation Obesity syndromesPCSK1 (PC1)Morbid obesity, hypocortisolism, hypoinsulinemiaJackson et al [1997], Jackson et al [2003] LEPMorbid obesityStrobel et al [1998] LEPRClément et al [1998] Prader-Willi syndromeLoss of paternal 15q11.2Hypotonia in infancy, developmental delay, cryptorchidism/microphallus in males, abnormal satiety, intellectual disabilityCassidy et al [2012] TUBB3 E410K syndrome (see Tubulinopathies Overview)TUBB3Congenital fibrosis of the extraocular muscles, facial weakness, developmental delay, sensorimotor polyneuropathy, stereotyped midface hypoplasia, intellectual disabilities & vocal cord paralysis, tracheomalacia & cyclic vomitingChew et al [2013], Balasubramanian et al [2015] X-linked adrenal hypoplasia congenitaNR0B1Adrenal failure Xp22.3 contiguous gene deletion syndromeXp22.3 microdeletionKS, icthyosis, short stature, intellectual disability, chondrodysplasia punctata, digital synkinesiaBick et al [1989], Hou [2005] 1\. At least 19 genes are associated with BBS: ARL6, BBIP1, BBS1, BBS2, BBS4, BBS5, BBS7, BBS9, BBS10, BBS12, CEP290, IFT27, LZTFL1, MKKS, MKS1, SDCCAG8, TRIM32, TTC8, and WDPCP. ### Differential Diagnosis of IGD at Specific Developmental Stages Infancy. Although males with IGD may have cryptorchidism and/or microphallus at birth, these features are not specific for IGD. Numerous disorders can give rise to these genital defects, ranging from isolated findings to syndromes such as Prader-Willi syndrome or abnormal pituitary development (see PROP1-Related Combined Pituitary Hormone Deficiency). This is particularly true for cryptorchidism, the most common birth defect of the male genitalia. Adolescence. Perhaps the most difficult distinction to make is between IGD and constitutional delay of puberty (CDP). Time is a critical factor in distinguishing between these two conditions. In CDP, spontaneous and otherwise normal puberty eventually occurs, whereas in IGD spontaneous sexual maturation does not occur at any time. Evidence suggests that CDP and IGD are not discrete clinical entities but rather are part of a phenotypic spectrum. In families with IGD, delayed puberty occurs at a much higher frequency in otherwise "normal" family members than in the general population, suggesting that CDP may represent a milder clinical variant of the IGD phenotype [Waldstreicher et al 1996, Pitteloud et al 2006a]. Although the distinction between CDP and IGD cannot be reliably made at any age, age 18 years has traditionally been suggested as the age at which IGD can be diagnosed; however, the recent description of IGD "reversal" occurring in persons in their 20s and later raises the possibility that such individuals may have a severe form of CDP [Raivio et al 2007]. In contrast, the presence of other clinical features associated with IGD (e.g., anosmia, synkinesia) (Table 3) may result in a diagnosis of IGD being made before age 18 years. Currently, no clinically available test can reliably differentiate CDP from IGD. Data analyses have suggested that the mean serum concentrations of LH and sex hormones after GnRH or hCG (human chorionic gonadotropin) stimulation vary significantly between individuals with CDP and those with IGD. However, the clinical utility of measuring serum LH and sex hormone concentrations after stimulation with GnRH and hCG is limited by the significant variation in individual LH and sex hormone serum concentrations, resulting in considerable overlap between groups [Degros et al 2003]. A peak-to-basal ratio of free alpha subunit (FAS) after the administration of GnRH has been proposed to help distinguish between CDP and IGD with a sensitivity and specificity in the 95% range and an overlap rate of 10% [Mainieri & Elnecave 2003]. More recently, combining a 19-day hCG test with a conventional GnRH test has also been proposed to improve the differentiation between IGD and CDP [Segal et al 2009]. However, given the relatively small number of individuals studied and limited follow-up in both studies, prospective validation is required to determine the true diagnostic reliability of the above tests. Figure 1 and Figure 2 provide testing algorithms for establishing the diagnosis of isolated GnRH deficiency in males and females, respectively. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs of an individual diagnosed with IGD, the following evaluations are recommended: * Assessment of clinical manifestations of hypogonadism based on the age and sex of the individual, if not already performed as part of the diagnostic work up (see Diagnosis and Table 1) * Assessment of laboratory findings* of hypogonadotropic hypogonadism if not already performed as part of the diagnostic work up * Serum concentration of LH (luteinizing hormone) and FSH (follicle-stimulating hormone) and in males total testosterone (T) <100 ng/dL and in females estradiol (E2) <50 pg/mL * Assessment for presence of possible non-reproductive features including: renal ultrasound examination (to detect unilateral renal agenesis), hearing tests (to detect sensorineural hearing loss), skeletal survey (to detect limb/spine bony abnormalities), dental exam (to detect dental agenesis), eye exam (to detect iris and/or chorioretinal coloboma) and developmental assessment (if there is evidence of developmental delay) * In addition to assessing the degree of hypogonadism/GnRH deficiency, potential deterioration in bone health that may have resulted from periods of low-circulating sex hormones needs to be addressed. Depending on the timing of puberty, duration of GnRH deficiency, and other osteoporotic risk factors (e.g., glucocorticoid excess, smoking), one should consider obtaining a bone mineral density study (see Prevention of Secondary Complications). * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations An expert European consensus statement on the management of IGD has recently been published [Boehm et al 2015] (full text). Typically, a definitive diagnosis of IGD is made around age 18 years. Occasionally, however, a high clinical suspicion of IGD may be present in an adolescent presenting with anosmia and delayed puberty or in an infant with microphallus and cryptorchidism. #### Males with IGD Age ≥18 Years Treatment options include sex steroids, gonadotropins, and pulsatile GnRH administration. Choice of therapy in adults is determined by the goal(s) of treatment (i.e., to induce and maintain secondary sex characteristics and/or to induce and maintain fertility). The selection of hormone replacement therapy is also based on the preference of the individual being treated; however, when fertility is not immediately desired, replacement with testosterone therapy is the most practical option. As the majority of individuals with IGD have not progressed through puberty at the time of diagnosis, initial therapy should be started at low doses and gradually increased to adult doses once the development of secondary sexual characteristics is achieved. Hormone replacement therapy for males not desiring fertility * Testosterone therapy in the form of injectable and transdermal routes of testosterone administration is typically used to both induce puberty and maintain adult levels of testosterone. Recently nasal testosterone has become available but use has not been reported in patients with IGD. The injectable testosterone preparations have a "roller-coaster" pharmacokinetic effect, with peak and trough levels that can go to extraphysiologic levels; thus, the transdermal preparations have the added benefit of offering a more favorable pharmacokinetic profile. A typical adult dose of testosterone replacement is 200 mg of testosterone ester injection every two weeks or 5 g of a 1% testosterone gel every day. Doses do vary with newer testosterone preparations; manufacturer’s instructions should be followed for individual testosterone preparations. Men using topical androgen replacement must take care to avoid exposing other individuals to treated skin. Anecdotal reports suggest that the transmission of clinically effective levels of testosterone from the patient to other family members (including women and children) is possible with undesirable side effects. Once puberty is initiated, testosterone replacement therapy is usually required indefinitely to ensure normal sexual function and maintenance of proper muscle, bone, and red blood cell mass. However, in approximately 10% of males, reversal of IGD may occur; thus, if clinical evidence shows endogenous activity of the hypothalamo-pituitary-axis (e.g., testicular growth on testosterone, maintained testosterone levels despite missing/withholding therapy), a brief washout of testosterone therapy should be done with monitoring of testosterone levels. If testosterone levels fall, therapy should be reinitiated. If levels are normal, no further testosterone therapy will be required; serial monitoring of levels should be undertaken, as some individuals may require reinitiation of therapy. * Human chorionic gonadotropin (hCG). An alternative to testosterone therapy, hCG injections promote testicular growth, normalize serum concentration of testosterone, and induce development of secondary sexual characteristics. In adults, treatment with hCG is usually initiated at 1,500 IU intramuscularly or subcutaneously every other day to normalize serum testosterone concentrations. Dose should be increased by increments of 250 IU if serum testosterone levels remain low. Treatment with hCG must be weighed against the increased risk of developing gynecomastia (resulting from the estrogen produced by stimulation of the testes with hCG). To some extent the risk of gynecomastia can be minimized by gradually reducing the dose of hCG to the minimum required to sustain a serum testosterone concentration in the mid-normal range (~500 ng/dL). #### Male Infants/Adolescents with Suspicion of IGD If IGD is clinically suspected (e.g., low testosterone levels with low/normal gonadotropins) low-dose testosterone or hCG therapy can be given in early infancy to boys with microphallus to increase penile length [Bin-Abbas et al 1999, Young 2012]. Since a definitive diagnosis of IGD may not be possible until age 18 years, after infancy these boys do not generally need to be treated until around the time of puberty. At this time, if a high suspicion of IGD remains (e.g., associated anosmia and delay in onset puberty), these subjects may benefit from early initiation of hormonal replacement therapy with either testosterone or hCG treatment early in the pubertal period. A suggestive puberty induction regimen in adolescents is to start a long-acting testosterone ester at a dose of 25-50 mg, given intramuscularly every two weeks. The doses can be gradually increased by 25-50 mg every two to three months until full virilization is achieved. Once adult doses (~200 mg/2 weeks) are reached, further adjustments are based on serum testosterone levels. Hormone replacement therapy for males desiring fertility (fertility induction in males). As testosterone replacement therapy suppresses spermatogenesis in the testes, gonadotropins or pulsatile GnRH therapy is usually required to realize the fertility potential in males. * Gonadotropin therapy. In most males with IGD, a combination of gonadotropins (hCG along with either human menopausal gonadotropins [hMG] or recombinant FSH) is used to stimulate spermatogenesis. In males with very low testicular volumes (≤~8 mL) the initiating dose of hCG is usually 1,500 IU intramuscularly or subcutaneously every other day; FSH is added at doses ranging from 37.5 to 75 IU as either hMG or recombinant formulation. Trough serum testosterone concentrations (target: mid-normal range [~500 ng/dL]), trough serum FSH levels (target: mid-normal reference range), and sperm count are monitored to assess response. Recent trials show that in those with lower testicular volumes, priming with FSH prior to combination therapy may improve spermatogenic outcomes [Dwyer et al 2013]. In males with higher baseline testicular volumes, treatment with hCG alone may be sufficient to achieve spermatogenesis and conception [Burris et al 1988]. However, if after six to nine months, semen analysis reveals persistent azoospermia or marked oligospermia, FSH is added to the regimen at doses ranging from 37.5 to 75 IU as either hMG or a recombinant formulation. In either treatment, testicular volume must be tracked, as this is one of the primary determinants of successful spermatogenesis. In fact, sperm are rarely seen in the semen analysis until testicular volume reaches 8 mL [Whitcomb & Crowley 1990]. In most males without a history of cryptorchidism, sperm function is usually normal and conception can occur even with relatively low sperm counts. Note: Liu et al [2009] have noted that previous treatment with gonadotropins may reduce the period of subsequent gonadotropin treatment required for initiation of spermatogenesis. If a pituitary defect exists, gonadotropin therapy becomes the treatment of choice. * Pulsatile GnRH stimulation vs. gonadotropin therapy. While either gonadotropin therapy or pulsatile GnRH stimulation can induce spermatogenesis in approximately 90%-95% of men with IGD, some men have a better response to pulsatile GnRH stimulation than to gonadotropin therapy. Subcutaneous administration of GnRH in a pulsatile manner through a portable pump that delivers a GnRH bolus every two hours is an efficient way of inducing testicular growth and spermatogenesis [Pitteloud et al 2002b]. As the primary defect of IGD is typically localized to the hypothalamus, the pituitary responds appropriately to physiologic doses of GnRH. Note: In the US, pulsatile GnRH therapy is not currently approved by the Food and Drug Administration for the treatment of infertility in men and, thus, is available for such treatment only at specialized research centers. #### Females with IGD Hormone replacement therapy for females not desiring fertility. Although a definitive diagnosis of IGD in females is usually made around age 18 years, occasionally a high clinical suspicion of IGD may be present in an adolescent presenting with anosmia and delayed puberty, and therapy may need to be initiated earlier (age ~14 years) * To allow optimal breast development, initial treatment should consist of unopposed estrogen replacement via oral or topical preparations. Many formulations of estrogens are available; a suggested oral regimen is using premarin 0.3 mg daily to be increased gradually to an adult replacement dose of 1-1.25 mg daily. * Once breast development is optimal, a progestin should be added for endometrial protection (e.g., cyclical Prometrium® 200 mg daily for 10-12 days). * Although preference of the individual plays an important role in choice of treatment plan, low-estrogen formulations should be considered in women with clotting abnormalities (see Factor V Leiden Thrombophilia and Prothrombin Thrombophilia). Hormone replacement therapy for females desiring fertility (fertility induction in females). Pulsatile GnRH stimulation and exogenous gonadotropins are FDA approved for folliculogenesis in women with IGD. Either therapy should be administered with close supervision by physicians specializing in ovulation induction. Intravenous administration of GnRH at various frequencies throughout the menstrual cycle closely mimics the dynamics of normal menstrual cycles resulting in ovulation of a single follicle [Santoro et al 1986]. This therapy offers a clear advantage over the traditional treatment with exogenous gonadotropins, which results in higher rates of both multiple gestation and ovarian hyperstimulation syndrome. For either approach, however, the rate of conception is approximately 30% per ovulatory cycle [Martin et al 1990]. #### Fertility Options in Patients with IGD if Fertility Induction is Unsuccessful In vitro fertilization. Although successful spermatogenesis can be obtained in most males with IGD through pulsatile GnRH therapy or combined gonadotropin therapy, some men with KS caused by an ANOS1 (KAL1) pathogenic variant may have an atypical response to therapy [Sykiotis et al 2010a]. In those who respond to therapy, low sperm numbers can often result in conception; however, if infertility continues despite successful spermatogenesis or if spermatogenesis fails to occur, in vitro fertilization (IVF) is an option. Similarly, if spontaneous conception fails to occur in women with IGD who have undergone ovulation induction, IVF may be an option. ### Prevention of Secondary Complications Optimal calcium and vitamin D intake should be encouraged and specific treatment for decreased bone mass with bisphosphonates should be considered depending on the degree of bone mineralization (see Evaluations Following Initial Diagnosis). ### Surveillance Children of both sexes with findings suggestive of IGD (e.g., microphallus, anosmia) should be monitored at regular intervals from age 11 years onwards with the following: * Assessment of sexual maturation by Tanner staging (Table 1) * Measurement of serum concentrations of LH, FSH, and total testosterone (T) in males and estradiol (E2) in females * Bone age determinations In individuals with a confirmed diagnosis of IGD, serum sex steroid levels (to guide optimal hormone replacement) and bone mineral density should be monitored at regular intervals. ### Evaluation of Relatives at Risk It is appropriate to evaluate apparently asymptomatic older and younger at-risk relatives of an affected individual in order to identify as early as possible those who would benefit from surveillance and prompt initiation of treatment. Evaluations can include: * Molecular genetic testing if the pathogenic variant(s) in the family are known. However, a prepubertal child with a known pathogenic variant may progress through puberty in a normal fashion, delayed fashion, or not at all. Therefore, reevaluation of such individuals over time is important, and hormone treatment should be initiated only when IGD with impaired pubertal development is diagnosed. * If the pathogenic variant(s) in the family are not known, clinical review of at-risk relatives of pubertal age to assess clinical onset of signs of puberty and if delayed, to initiate appropriate therapy for pubertal induction. 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	Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency	c0342384	25,003	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1334/	2021-01-18T21:17:10	{"mesh": ["C562785"], "synonyms": ["Idiopathic Hypogonadotropic Hypogonadism", "Isolated Hypogonadotropic Hypogonadism"]}
Melanoma and neural system tumor syndrome is an extremely rare tumor association characterized by dual predisposition to melanoma and neural system tumors (typically astrocytoma; see this term). ## Epidemiology Prevalence and incidence rates are not known. Fewer than 20 affected families have been reported to date. Cases have been reported from France, Italy, the UK and the USA. ## Clinical description In reported families, affected individuals had cutaneous melanoma in association with dysplastic nevi, astrocytoma, benign or malignant peripheral nerve sheath tumor, neurofibroma, medulloblastoma, glioblastoma multiforme, ependymoma, glioma, and meningioma (see these terms). In some cases, melanoma was described first followed by nervous system tumors, and in other cases, melanoma was a secondary cancer. ## Etiology The etiology of this tumor association is unknown. Genetic mutations or germline deletions are thought to underlie this cancer susceptibility syndrome. ## Genetic counseling Male-to-male transmission was reported in one family but inheritance patterns are not clearly characterized. The increased risk appears to be found in both first- and second-degree relatives. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Melanoma and neural system tumor syndrome	c1835042	25,004	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=252206	2021-01-23T17:44:27	{"gard": ["8468"], "mesh": ["C536149"], "omim": ["155755"], "umls": ["C1835042"], "synonyms": ["Melanoma-astrocytoma syndrome"]}
Morgagni-Stewart-Morel (MSM) syndrome is a disorder characterized by thickening of the frontal bone of the skull (hyperostosis frontalis interna), as well as obesity and excessive hair growth (hypertrichosis). Other signs and symptoms may include seizures, headaches, diabetes insipidus, and sex gland disturbances. The cause of Morgagni-Stewart-Morel syndrome is not fully understood. Some instances of dominant inheritance have been reported, but whether it is autosomal dominant or X-linked dominant is not known. Treatment may include medication for headaches and seizures and surgery to remove the excessive bone of the skull. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Morgagni-Stewart-Morel syndrome	c0020494	25,005	gard	https://rarediseases.info.nih.gov/diseases/8593/morgagni-stewart-morel-syndrome	2021-01-18T17:59:00	{"mesh": ["D006957"], "omim": ["144800"], "orphanet": ["77296"], "synonyms": ["MSM syndrome", "Hyperostosis frontalis interna, obesity, shortness and cognitive impairment"]}
A number sign (#) is used with this entry because of evidence that trichodentoosseous syndrome (TDO) is caused by heterozygous mutation in the DLX3 gene (600525) on chromosome 17q21. Description Trichodentoosseous syndrome is an autosomal dominant disorder with complete penetrance characterized by abnormalities involving hair, teeth, and bone (summary by Nguyen et al., 2013). Clinical Features Robinson and Miller (1966) described autosomal dominant inheritance of enamel hypoplasia and hypocalcification with associated strikingly curly hair. Lichtenstein et al. (1972) traced the same condition through 6 generations of an Irish-American family. Affected members of this family had a feature not described by Robinson and Miller (1966)--mild increase in bone density, particularly in the skull. The fingernails showed either laminated splitting of the superficial layers or thick cornification. Apparently both keratin and enamel are defective. Crawford (1970) probably reported the same condition. He stated that his case had very curly blond, dry hair (Jorgenson, 1975). The family reported by Winter et al. (1969) probably had TDO syndrome. Taurodontism ('bull teeth') occurs in this condition (see 272700). The family described by Lichtenstein et al. (1972) lived mainly in Washington County, Virginia. Quattromani et al. (1983) described a presumably unrelated family from the Holston River Valley of neighboring Tennessee. The changes in the teeth and brain were similar to those in the original family but the skeletal findings were different: sclerosis and thickening of the calvaria with long bones that showed subtle undertubulation but no sclerosis. The authors suggested that the same gene might be present in the Tennessee family with modification by gene or genes present in one kindred and not in the other. Shapiro et al. (1983) suggested that more than one fundamentally distinct entity may be subsumed by the designation TDO syndrome. Previously, 2 possibly distinct types had been reported. TDO-I (Lichtenstein et al., 1972) is characterized by kinky or curly hair, dolichocephaly, enamel hypoplasia, increased dental caries, radial dense bones, and occasionally brittle nails. The chondrocranium shows some thickening but calvarial density and thickness are normal. Premature fusion of cranial sutures, especially the sagittal, is responsible for dolichocephaly. Persons with TDO-II (Leisti and Sjoblom, 1978) show sparse as well as curly hair, more striking nail changes, and thickening and sclerosis of the calvaria. Males show narrowing of the ear canal. Dental eruption is delayed in TDO-I and precocious in TDO-II. In TDO-II, dentin is dysplastic whereas it is normal in TDO-I. Shapiro et al. (1983) described a family that differed from both of these. Affected persons showed macrocephaly and obliterated diploe and no long bone sclerosis. Crawford and Aldred (1990) pointed out that the dental changes of amelogenesis imperfecta, hypomaturation-hypoplasia type with taurodontism (AI4; 104510), (Congleton and Burkes, 1979; Crawford et al., 1988) are identical to those in TDO, from which it is distinguished only by the absence of changes in the hair or osteosclerosis. Crawford et al. (1988) observed in the same kindred 2 apparent subtypes of amelogenesis with taurodontism differentiated by the thickness of the enamel and the overall tooth size. Seow (1993) insisted, however, that TDO and amelogenesis imperfecta should not be confused. True taurodontism is indicated, she concluded, by a change in the mandibular first permanent molars and this occurs only in the TDO syndrome. In western North Carolina, Wright et al. (1997) characterized the phenotypic variation in 3 kindreds with a total of 33 affected members. All TDO individuals with teeth had generalized thin and/or pitted enamel hypoplasia. Taurodontism was present in all affected individuals, but was variably expressed. Unique kinky/curly hair at birth was reported in 85% of affected individuals. The curly hair phenotype was retained past infancy in 46% of affected individuals. Thick cranial bones, lack of visible pneumatization of the mastoid processes, and/or obliteration of the calvarial diploe was seen in 97% of affected persons compared with 30% of the unaffected members of these kindreds. The ABO, Kell, and Gc loci, previously suggested to be linked to TDO, were excluded as candidates in these 3 kindreds. Wright et al. (1997) noted that 1 of the families reported by Congleton and Burkes (1979) was related to their North Carolina kindred and that the other 2 families reported by Congleton and Burkes (1979) lived in close proximity. Hart et al. (1997, 1997) studied the 3 families previously reported by Wright et al. (1997) and another family with TDO and found that 2 clinical features, taurodontism and enamel hypoplasia, were fully penetrant in all 39 TDO-affected individuals, while bone and hair features were variably expressed. Nguyen et al. (2013) compared craniofacial variation between 53 TDO-affected individuals and 34 unaffected members of 8 families from 1 kindred and observed marked variation in most of the cranial features measured. The position of the maxilla in relation to the cranial base was more retrusive in TDO-affected individuals compared to unaffected individuals. The authors noted that although patients with TDO are often described as having prognathic mandibles, they found no difference in mandibular projection between patients and controls; however, the relative position of a normal growing mandible would appear more prognathic when aligned next to a retrusive maxilla. TDO-affected individuals also had significantly longer mandibular body length and shorter ramus height, with no difference in gonial angle. Nguyen et al. (2013) stated that a shorter ramus height can mask mandibular projection even when a significant increase in body length is present. Mapping Adding another family to the 3 reported by Wright et al. (1997), Hart et al. (1997, 1997) investigated 4 families with a total of 39 TDO-affected members. Using a genomewide search strategy, they found linkage of TDO syndrome to markers on chromosome 17q21; maximum lod = 10.54 at theta = 0.00 for D17S791, with no indication of genetic heterogeneity. Linkage analysis and haplotype reconstruction allowed them to sublocalize the TDO syndrome locus to a 12-cM interval flanked by D17S932 and D17S809. Molecular Genetics Price et al. (1998) noted that 2 members of the distal-less homeobox gene family, DLX3 and DLX7 (601911), map to the same region as TDO, namely, chromosome 17q21. They described genomic cloning and sequencing of both the human DLX3 and DLX7 genes and identified a 4-bp deletion in human DLX3 (600525.0001) which correlated with the TDO phenotype in 6 families. The observed mutation was predicted to cause a frameshift and premature termination codon, resulting in a functionally altered DLX3 protein. The finding of a human mutation in a DLX gene was consistent with murine studies indicating their important role in the development of hair, teeth, and bone. Price et al. (1998) identified the same 4-bp deletion in a Virginia family. A common haplotype for 3 markers surrounding the DLX3 gene was identified in all affected subjects in the 6 original families and the Virginia family. Price et al. (1998) concluded that all affected individuals in these families had inherited the same DLX3 gene deletion from a common ancestor. They also concluded that the variable clinical phenotype observed in these families that share a common mutation suggested clinical variability is not the result of genetic heterogeneity at a major locus, but may reflect genetic heterogeneity at other epigenetic loci or contributing environmental factors or both. By searching for DLX3 or DLX7 mutations in 3 members (2 affected and 1 unaffected) of a family with amelogenesis imperfecta, Price et al. (1999) approached the question of whether TDO syndrome and AIHHT are allelic disorders. Sequence analyses of the DLX3 and DLX7 genes suggested that that form of amelogenesis is not due to genetic mutations or polymorphisms in the exons of these genes and that it is an entity distinct from TDO. Dong et al. (2005) studied a family in which affected members had the characteristic dental phenotype but no hair or bone abnormalities, a condition the authors classified as AIHHT, and they identified a 2-bp deletion in the DLX3 gene (560delCT; 600525.0002). In 7 affected members of a 3-generation family with an attenuated TDO phenotype, Wright et al. (2008) identified heterozygosity for the 560delCT mutation in the DLX3 gene. The authors stated that all affected individuals in this kindred had coarse unmanageable hair with a diminished shaft diameter similar to that seen in individuals with the 4-bp deletion (600525.0001), and that alterations in tooth size and the severity of taurodontism were less severe and bone changes less marked than those seen in individuals with the 4-bp deletion. Wright et al. (2008) concluded that this mutation causes TDO with an attenuated phenotype, not AIHHT, as previously reported. INHERITANCE \- Autosomal dominant HEAD & NECK Head \- Dolichocephaly Face \- Frontal bossing Teeth \- Thin enamel \- Small, widely spaced teeth \- Teeth pits \- Taurodontism \- Periapical abscesses SKELETAL \- Increased bone density, mild-moderate (skull, spine, long bones) Skull \- Obliteration of calvarial diploe \- Poorly pneumatized mastoids SKIN, NAILS, & HAIR Nails \- Brittle nails Hair \- Kinky hair MISCELLANEOUS \- Hair tends to straighten by 2nd-3rd decade MOLECULAR BASIS \- Caused by mutations in the distal-less homeo box-3 gene (DLX3, 600525.0001 ) ▲ 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	TRICHODENTOOSSEOUS SYNDROME	c0265333	25,006	omim	https://www.omim.org/entry/190320	2019-09-22T16:32:24	{"mesh": ["C536549"], "omim": ["190320"], "orphanet": ["3352"], "synonyms": ["Alternative titles", "TDO SYNDROME"]}
For a phenotypic description and a discussion of genetic heterogeneity of photoparoxysmal response, see PPR1 (132100). Mapping By linkage analysis of 25 families in which at least 2 sibs were affected with either PPR or traits of idiopathic generalized epilepsy (IGE; see 600669), Tauer et al. (2005) identified a putative disease locus on chromosome 13q31.3 (MOD score of 3.64 at marker D13S1230 under a recessive mode of inheritance). Of 121 family members, 68 displayed PPR and 69 had IGE or unprovoked generalized spike-wave discharges on EEG. Fifty-eight (84%) of the 69 individuals with IGE also showed PPR. The MOD score increased to a maximum of 4.83 when using additional trait definitions more specific for IGE traits, suggesting that the locus on 13q31 is related to IGE and may represent a gene involved in a common epileptogenic pathway shared by both PPR and IGE. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	PHOTOPAROXYSMAL RESPONSE 2	c0393720	25,007	omim	https://www.omim.org/entry/609572	2019-09-22T16:05:52	{"doid": ["0060281"], "mesh": ["D020195"], "omim": ["609572"], "orphanet": ["166409"], "synonyms": ["Alternative titles", "PHOTOPAROXYSMAL RESPONSE WITH OR WITHOUT IDIOPATHIC GENERALIZED EPILEPSY"]}
Ganglioneuroblastoma MRI of a ganglioneuroblastoma found in the head and neck of a 7 year old Caucasian male. SpecialtyOncology Ganglioneuroblastoma is a variant of neuroblastoma that is surrounded by ganglion cells. It can be difficult to diagnose.[1] Nodular ganglioneuroblastoma can be divided by prognosis.[2] ## Contents * 1 Neuroblastic tumors * 2 See also * 3 References * 4 External links ## Neuroblastic tumors[edit] It is contained within the neuroblastic tumors group, which includes:[3] * Ganglioneuroma (benign) * Ganglioneuroblastoma (intermediate). * Neuroblastoma (aggressive) ## See also[edit] * Neuroblastoma ## References[edit] 1. ^ Gasparetto EL, Rosemberg S, Matushita H, Leite Cda C (June 2007). "Ganglioneuroblastoma of the cerebellum: neuroimaging and pathological features of a case". Arq Neuropsiquiatr. 65 (2A): 338–40. doi:10.1590/s0004-282x2007000200029. PMID 17607440. 2. ^ Peuchmaur M, d'Amore ES, Joshi VV, et al. (November 2003). "Revision of the International Neuroblastoma Pathology Classification: confirmation of favorable and unfavorable prognostic subsets in ganglioneuroblastoma, nodular". Cancer. 98 (10): 2274–81. doi:10.1002/cncr.11773. PMID 14601099. 3. ^ Shimada H, Ambros IM, Dehner LP, Hata J, Joshi VV, Roald B (July 1999). "Terminology and morphologic criteria of neuroblastic tumors: recommendations by the International Neuroblastoma Pathology Committee". Cancer. 86 (2): 349–63. doi:10.1002/(sici)1097-0142(19990715)86:2<349::aid-cncr20>3.0.co;2-y. PMID 10421272. ## External links[edit] Classification D * ICD-O: M9490/3 * MeSH: D018305 External resources * MedlinePlus: 001436 * Ganglioneuroblastoma (humpath.com) * 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]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Ganglioneuroblastoma	c0206718	25,008	wikipedia	https://en.wikipedia.org/wiki/Ganglioneuroblastoma	2021-01-18T18:32:57	{"mesh": ["D018305"], "umls": ["C0206718"], "orphanet": ["251877"], "wikidata": ["Q5521151"]}
A number sign (#) is used with this entry because of evidence that gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy (GDRM) is caused by homozygous mutation in the PPP2R3C gene (615902) on chromosome 14q13. Heterozygous PPP2R3C mutations in males cause teratozoospermia with reduced fertility (SPGF36; 618420). Description GDRM is characterized by 46,XY complete gonadal dysgenesis in association with extragonadal anomalies, including low birth weight, typical facial gestalt, rod and cone dystrophy, sensorineural hearing loss, omphalocele, anal atresia, renal agenesis, skeletal abnormalities, dry and scaly skin, severe myopathy, and neuromotor delay (Guran et al., 2019). Clinical Features Guran et al. (2019) reported 4 unrelated 46,XY females from consanguineous Turkish families with syndromic complete gonadal dysgenesis. The genital phenotype was female with hypoplastic labia majora; uterus was present in 3 patients and a primitive bicornuate uterus was detected in the fourth patient. All 4 exhibited similar facial dysmorphism, with flat face, sparse arched eyebrows, epicanthal folds, beaked nose with hypoplastic alae nasi, long smooth philtrum, thin lips with narrow mouth opening, and low-set, posteriorly rotated ears with overfolded helix. They had unruly hair with frontal upsweep and unusual hair whorls, and skin was dry and scaly. All 4 had lacrimal puncta hypoplasia and rod-cone dystrophy. Of 3 patients who had auditory testing, 2 showed sensorineural hearing loss. All exhibited severe myopathy with thick, stiff muscles; patients 2 and 3 underwent electromyography that revealed severe diffuse myopathy. Skeletal findings included short stature, delayed bone age, and limited elbow extension, and all 4 exhibited neuromotor delay. Patients 2 and 4 underwent gonadectomy; histologic analysis showed few to no Leydig cells and peripherally located Mullerian-like tubular structures in loose connective tissue containing vessels and peripheral nerve bundles. Patient 3 was a 19-year-old woman who had no gonads seen on laparoscopy at age 13.75 years and was given estrogen replacement therapy starting at age 14; she had Tanner stage 2 breast development at age 14.5, Tanner stage 2 pubic hair at age 17.5, and underwent menarche at age 18. All of the families had a history of multiple infertile couples, and semen analysis in 3 of the probands' fathers revealed teratozoospermia (see SPGF36; 618420). The fourth father did not undergo testing, and other relatives were unavailable for testing. One heterozygous mother reported oligomenorrhea and hypomenorrhea with normal pelvic ultrasound, and another mother underwent menopause at age 44 years. Molecular Genetics In 4 unrelated 46,XY females from consanguineous Turkish families with syndromic complete gonadal dysgenesis, Guran et al. (2019) identified homozygosity for 3 different missense mutations in the PPP2R3C gene (615902.0001-615902.0003) that segregated with disease in each family and were not found in ethnically matched controls or in public variant databases. The heterozygous fathers exhibited morphologic abnormalities of spermatozoa and reduced fertility (SPGF36). INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature Weight \- Low birth weight HEAD & NECK Head \- Flat vertex Face \- Flat face \- Long philtrum \- Smooth philtrum \- Narrow forehead (in some patients) \- Metopic ridge (in some patients) Ears \- Low-set ears \- Posteriorly rotated ears \- Overfolded helix \- Narrow elongated intertragic notch \- Sinus under tip of intertragic angle \- Sensorineural hearing loss (in some patients) Eyes \- Arched eyebrows \- Sparse eyebrows \- Bilateral epicanthal folds \- Rod-cone dystrophy \- Lacrimal puncta hypoplasia Nose \- Beaked nose \- Hypoplastic alae nasi \- 'Squashed down' appearance of nose, mild (in some patients) Mouth \- Thin lips \- Narrow mouth opening Teeth \- Hypodontia ABDOMEN External Features \- Omphalocele (in some patients) \- Diastasis recti Gastrointestinal \- Pyloric stenosis \- Anal atresia GENITOURINARY \- Complete gonadal dysgenesis \- Complete 46,XY female External Genitalia (Female) \- Hyoplastic labia majora Internal Genitalia (Female) \- Uterus present \- Primitive bicornuate uterus (in some patients) \- Gonadal tissue shows few to no Leydig cells mixed with Mullerian-like tubular structures (in some patients) \- Absent gonads (in some patients) Kidneys \- Unilateral renal agenesis (in some patients) SKELETAL \- Delayed bone age Spine \- Scoliosis (rare) Pelvis \- Hip dysplasia (rare) Limbs \- Limited elbow extension Hands \- Short hands \- Broad hands \- Interphalangeal webbing \- Bifid distal phalanx of thumb (rare) Feet \- Bifid distal phalanx of toe (rare) SKIN, NAILS, & HAIR Skin \- Dry skin \- Scaly skin \- Single horizontal palmar crease Hair \- Unruly scalp hair \- Frontal upsweep \- Unusual hair whorls \- Sparse pubic hair \- Absent axillary hair MUSCLE, SOFT TISSUES \- Severe myopathy \- Diffuse myopathy seen on EMG \- Muscular habitus \- Thick muscles \- Stiff muscles NEUROLOGIC Central Nervous System \- Neuromotor delay \- Corpus callosum agenesis \- Plaques in bilateral ventricular ependyma \- Punctate calcifications ENDOCRINE FEATURES \- Hormone evaluation consistent with complete gonadal dysgenesis \- Elevated follicle-stimulating hormone \- Elevated luteinizing hormone \- No rise in testosterone after human chorionic gonadotropin (hCG) stimulation \- Low antimullerian hormone (AMH) \- Normal or low-normal dehydroepiandrosterone (DHEA) \- Low or low-normal androstenedione LABORATORY ABNORMALITIES \- Elevated creatine kinase levels MISCELLANEOUS \- Male heterozygotes exhibit teratozoospermia and may have reduced fertility (see SPGF36, 618420 ) MOLECULAR BASIS \- Caused by mutation in the protein phosphatase 2, regulatory subunit B-double prime, gamma gene (PPP2R3C, 615902.0001 ) ▲ 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	GONADAL DYSGENESIS, DYSMORPHIC FACIES, RETINAL DYSTROPHY, AND MYOPATHY	None	25,009	omim	https://www.omim.org/entry/618419	2019-09-22T15:42:05	{"omim": ["618419"]}
Tinea barbae Other namesBarber's itch,[1] ringworm of the beard,[2] Tinea sycosis[1]:301 Tinea barbae or "barber's itch" SpecialtyInfectious disease Tinea barbae is a fungal infection of the hair. Tinea barbae is due to a dermatophytic infection around the bearded area of men. Generally, the infection occurs as a follicular inflammation, or as a cutaneous granulomatous lesion, i.e. a chronic inflammatory reaction. It is one of the causes of folliculitis. It is most common among agricultural workers, as the transmission is more common from animal-to-human than human-to-human. The most common causes are Trichophyton mentagrophytes and T. verrucosum. ## Contents * 1 Signs and symptoms * 2 Transmission * 3 Diagnosis * 4 Treatment * 5 References * 6 External links ## Signs and symptoms[edit] [3] Main symptoms that occur when affected with tinea barbae is pimple or blister amongst affected area, swelling and redness around infected area, red and lumpy skin on infected area.[4] Crusting around hairs in infected area will occur, hairs on infected area will also be effortless to pull out.[4] Tinea barbae can be itchy or painful to touch but these symptoms do not always occur.[4] ## Transmission[edit] The transmission of tinea barbae to humans occurs through contact of an infected animal to the skin of a human.[5] Infection can occasionally be transmitted through contact of infected animal hair on human skin. Tinea barbae is very rarely transmitted through human to human contact but is not completely impossible.[5] ## Diagnosis[edit] Diagnosis of tinea barbae will firstly include questions being asked from doctors about interactions with farm animals and lifestyle experiences.[5] Doctor will then gain knowledge on possible disease by microscopy, this is viewing the skin under a microscope to get an enlarge view of infected area. Skin scraping and removal of hairs on infected area will occur for medical examination.[4] To acquire causation of tinea barbae putting infected area under ultraviolet light can achieve this, as infection caused by animal and human contact will not show up as fluorescent under the ultraviolet light, compared to other causes of this disease.[5] ## Treatment[edit] Treatment can vary with severity of the infection. Moderate cases of tinea barbae can be treated with topical antifungal medications. Topical antifungal medications will come in the form of cream, which can normally be obtained over the counter. More serious cases of tinea barbae warrant an oral antifungal medication.[4] ## References[edit] 1. ^ a b James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. 2. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 518. ISBN 978-1-4160-2999-1. 3. ^ "Ringworm, Beard (Tinea Barbae) in Adults: Condition, Treatment and Pictures - Overview". skinsight.com. Retrieved 2016-05-17. 4. ^ a b c d e "Tinea Barbae". dermnetnz.org. DermNet NZ. 2003. Retrieved 5 December 2016. 5. ^ a b c d Rutecki; Wurtz & Thomson (2000), "From Animal to Man: Tinea Barbae", Current Infectious Disease Reports, 2 (5): 433–437, doi:10.1007/s11908-000-0073-1 ## External links[edit] Classification D * ICD-10: B35.0 (ILDS B35.040) * ICD-9-CM: 110.0 External resources * eMedicine: derm/419 * v * t * e Fungal infection and mesomycetozoea Superficial and cutaneous (dermatomycosis): Tinea = skin; Piedra (exothrix/ endothrix) = hair Ascomycota Dermatophyte (Dermatophytosis) By location * Tinea barbae/tinea capitis * Kerion * Tinea corporis * Ringworm * Dermatophytids * Tinea cruris * Tinea manuum * Tinea pedis (athlete's foot) * Tinea unguium/onychomycosis * White superficial onychomycosis * Distal subungual onychomycosis * Proximal subungual onychomycosis * Tinea corporis gladiatorum * Tinea faciei * Tinea imbricata * Tinea incognito * Favus By organism * Epidermophyton floccosum * Microsporum canis * Microsporum audouinii * Trichophyton interdigitale/mentagrophytes * Trichophyton tonsurans * Trichophyton schoenleini * Trichophyton rubrum * Trichophyton verrucosum Other * Hortaea werneckii * Tinea nigra * Piedraia hortae * Black piedra Basidiomycota * Malassezia furfur * Tinea versicolor * Pityrosporum folliculitis * Trichosporon * White piedra Subcutaneous, systemic, and opportunistic Ascomycota Dimorphic (yeast+mold) Onygenales * Coccidioides immitis/Coccidioides posadasii * Coccidioidomycosis * Disseminated coccidioidomycosis * Primary cutaneous coccidioidomycosis. Primary pulmonary coccidioidomycosis * Histoplasma capsulatum * Histoplasmosis * Primary cutaneous histoplasmosis * Primary pulmonary histoplasmosis * Progressive disseminated histoplasmosis * Histoplasma duboisii * African histoplasmosis * Lacazia loboi * Lobomycosis * Paracoccidioides brasiliensis * Paracoccidioidomycosis Other * Blastomyces dermatitidis * Blastomycosis * North American blastomycosis * South American blastomycosis * Sporothrix schenckii * Sporotrichosis * Talaromyces marneffei * Talaromycosis Yeast-like * Candida albicans * Candidiasis * Oral * Esophageal * Vulvovaginal * Chronic mucocutaneous * Antibiotic candidiasis * Candidal intertrigo * Candidal onychomycosis * Candidal paronychia * Candidid * Diaper candidiasis * Congenital cutaneous candidiasis * Perianal candidiasis * Systemic candidiasis * Erosio interdigitalis blastomycetica * C. auris * C. glabrata * C. lusitaniae * C. tropicalis * Pneumocystis jirovecii * Pneumocystosis * Pneumocystis pneumonia Mold-like * Aspergillus * Aspergillosis * Aspergilloma * Allergic bronchopulmonary aspergillosis * Primary cutaneous aspergillosis * Exophiala jeanselmei * Eumycetoma * Fonsecaea pedrosoi/Fonsecaea compacta/Phialophora verrucosa * Chromoblastomycosis * Geotrichum candidum * Geotrichosis * Pseudallescheria boydii * Allescheriasis Basidiomycota * Cryptococcus neoformans * Cryptococcosis * Trichosporon spp * Trichosporonosis Zygomycota (Zygomycosis) Mucorales (Mucormycosis) * Rhizopus oryzae * Mucor indicus * Lichtheimia corymbifera * Syncephalastrum racemosum * Apophysomyces variabilis Entomophthorales (Entomophthoramycosis) * Basidiobolus ranarum * Basidiobolomycosis * Conidiobolus coronatus/Conidiobolus incongruus * Conidiobolomycosis Microsporidia (Microsporidiosis) * Enterocytozoon bieneusi/Encephalitozoon intestinalis Mesomycetozoea * Rhinosporidium seeberi * Rhinosporidiosis Ungrouped * Alternariosis * Fungal folliculitis * Fusarium * Fusariosis * Granuloma gluteale infantum * Hyalohyphomycosis * Otomycosis * Phaeohyphomycosis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Tinea barbae	c2349994	25,010	wikipedia	https://en.wikipedia.org/wiki/Tinea_barbae	2021-01-18T18:58:46	{"icd-9": ["110.0"], "icd-10": ["B35.0"], "wikidata": ["Q1887877"]}
Trisomy 18, also called Edwards syndrome, is a chromosomal condition associated with abnormalities in many parts of the body. Individuals with trisomy 18 often have slow growth before birth (intrauterine growth retardation) and a low birth weight. Affected individuals may have heart defects and abnormalities of other organs that develop before birth. Other features of trisomy 18 include a small, abnormally shaped head; a small jaw and mouth; and clenched fists with overlapping fingers. Due to the presence of several life-threatening medical problems, many individuals with trisomy 18 die before birth or within their first month. Five to 10 percent of children with this condition live past their first year, and these children often have severe intellectual disability. ## Frequency Trisomy 18 occurs in about 1 in 5,000 live-born infants; it is more common in pregnancy, but many affected fetuses do not survive to term. Although women of all ages can have a child with trisomy 18, the chance of having a child with this condition increases as a woman gets older. ## Causes Most cases of trisomy 18 result from having three copies of chromosome 18 in each cell in the body instead of the usual two copies. The extra genetic material disrupts the normal course of development, causing the characteristic features of trisomy 18. Approximately 5 percent of people with trisomy 18 have an extra copy of chromosome 18 in only some of the body's cells. In these people, the condition is called mosaic trisomy 18. The severity of mosaic trisomy 18 depends on the type and number of cells that have the extra chromosome. The development of individuals with this form of trisomy 18 may range from normal to severely affected. Very rarely, part of the long (q) arm of chromosome 18 becomes attached (translocated) to another chromosome during the formation of reproductive cells (eggs and sperm) or very early in embryonic development. Affected individuals have two copies of chromosome 18, plus the extra material from chromosome 18 attached to another chromosome. People with this genetic change are said to have partial trisomy 18. If only part of the q arm is present in three copies, the physical signs of partial trisomy 18 may be less severe than those typically seen in trisomy 18. If the entire q arm is present in three copies, individuals may be as severely affected as if they had three full copies of chromosome 18. ### Learn more about the chromosome associated with Trisomy 18 * chromosome 18 ## Inheritance Pattern Most cases of trisomy 18 are not inherited, but occur as random events during the formation of eggs and sperm. An error in cell division called nondisjunction results in a reproductive cell with an abnormal number of chromosomes. For example, an egg or sperm cell may gain an extra copy of chromosome 18. If one of these atypical reproductive cells contributes to the genetic makeup of a child, the child will have an extra chromosome 18 in each of the body's cells. Mosaic trisomy 18 is also not inherited. It occurs as a random event during cell division early in embryonic development. As a result, some of the body's cells have the usual two copies of chromosome 18, and other cells have three copies of this chromosome. Partial trisomy 18 can be inherited. An unaffected person can carry a rearrangement of genetic material between chromosome 18 and another chromosome. This rearrangement is called a balanced translocation because there is no extra material from chromosome 18. Although they do not have signs of trisomy 18, people who carry this type of balanced translocation are at an increased risk of having children with the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Trisomy 18	c3537048	25,011	medlineplus	https://medlineplus.gov/genetics/condition/trisomy-18/	2021-01-27T08:25:52	{"gard": ["6321"], "mesh": ["D000073842"], "synonyms": []}
A rare, severe genetic arrhythmogenic disorder of the structurally normal heart characterized by catecholamine-induced ventricular tachycardia (VT) manifesting as syncope and sudden death in young individuals. ## Epidemiology The prevalence of catecholaminergic polymorphic ventricular tachycardia (CPVT) is estimated to be 1/10,000. Both sexes are equally affected. ## Clinical description Typical age of onset of CPVT is between 7 and 15 years of age. Exercise- or emotion-induced syncopal spells are frequently the first symptom. In a subset of patients (10-20%), the disease is clinically silent, presenting only in the event of sudden death. Up to one third of CPVT patients experience life-threatening arrhythmic events prior to starting treatment. The typical arrhythmias of CPVT are bidirectional VT, and, less frequently, supraventricular tachycardias. ## Etiology The disorder is genetically heterogeneous; in 70% of cases, the cardiac ryanodine receptor (RYR2, 1q43) gene is implicated with autosomal dominant inheritance. Mutations in the cardiac calsequestrin gene (CASQ2, 1p13.1) cause an autosomal recessive form of CPVT in 2% to 5% of patients, and in rare instances may cause autosomal dominant CPVT. Other, rarer genes causing CPVT include Trans-2,3-enoyl-CoA reductase-like (TECRL, 4q13.1), calmodulin-1 (CALM1 , 14q32.11), and cardiac triadin (TRDN, 6q22.31). ## Diagnostic methods Subjects with a family history of CPVT, or emotion- or exercise-induced sudden death or syncope should undergo exercise stress test and Holter monitoring. Given the reproducibility of arrhythmias, graded exercise stress test is of utmost diagnostic importance. Holter monitoring is also indicated for the rarer cases where acute emotion represents a more powerful trigger. Resting electrocardiogram is usually unremarkable. Cardiac imaging (echocardiogram and MRI) is unremarkable. ## Differential diagnosis The principal differential diagnoses are long QT syndrome (LQTS), arrhythmogenic right ventricular cardiomyopathy (ARVC), and Andersen-Tawil syndrome. ## Antenatal diagnosis Antenatal diagnosis can be performed in families with high penetrance and a highly lethal mutation. ## Genetic counseling Screening for the RYR2 mutation and CASQ2 mutation is indicated in all patients with confirmed or suspected CPVT. Screening forTECRL, CALM1, and TRDN mutations may be considered as a second-line analysis. According to the mutation identified, the appropriate genetic counseling should be offered to affected families. ## Management and treatment Lifestyle changes such as limitation of physical activity, avoidance of strong emotion and stressful environments should be recommended to all CPVT patients. Beta blockers (BB; particularly nadolol) are the first treatment option for patients with CPVT and the maximum tolerated dose should be administered to control arrhythmias. Flecainide, a sodium channel blocker, can be considered in patients with BB-resistant arrhythmias. Implantable cardioverter defibrillator (ICD) is recommended in CPVT patients who survived a cardiac arrest, and in those experiencing recurrent syncope or breakthrough arrhythmias despite compliance to an optimal medical treatment. ## Prognosis Although CPVT is a severe disease with high mortality if untreated, early diagnosis and adequate treatment can greatly increase life expectancy. Lifestyle modifications along with optimal medical therapy and ICD implantation in patients with recurrent symptoms portends a favorable prognosis. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Catecholaminergic polymorphic ventricular tachycardia	c1631597	25,012	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3286	2021-01-23T18:53:55	{"gard": ["4421"], "mesh": ["C536334"], "omim": ["604772", "611938", "614021", "614916", "615441"], "umls": ["C1631597"], "icd-10": ["I47.2"], "synonyms": ["Bidirectional ventricular tachycardia induced by catecholamine", "CPVT", "Malignant paroxysmal ventricular tachycardia", "Polymorphic ventricular tachycardia induced by catecholamines"]}
X-linked hyper IgM syndrome is a condition that affects the immune system and occurs almost exclusively in males. People with this disorder have abnormal levels of proteins called antibodies or immunoglobulins. Antibodies help protect the body against infection by attaching to specific foreign particles and germs, marking them for destruction. There are several classes of antibodies, and each one has a different function in the immune system. Although the name of this condition implies that affected individuals always have high levels of immunoglobulin M (IgM), some people have normal levels of this antibody. People with X-linked hyper IgM syndrome have low levels of three other classes of antibodies: immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin E (IgE). The lack of certain antibody classes makes it difficult for people with this disorder to fight off infections. Individuals with X-linked hyper IgM syndrome begin to develop frequent infections in infancy and early childhood. Common infections include pneumonia, sinus infections (sinusitis), and ear infections (otitis). Infections often cause these children to have chronic diarrhea and they fail to gain weight and grow at the expected rate (failure to thrive). Some people with X-linked hyper IgM syndrome have low levels of white blood cells called neutrophils (neutropenia). Affected individuals may develop autoimmune disorders, neurologic complications from brain and spinal cord (central nervous system) infections, liver disease, and gastrointestinal tumors. They also have an increased risk of lymphoma, which is a cancer of immune system cells. The severity of X-linked hyper IgM syndrome varies among affected individuals, even among members of the same family. Without treatment, this condition can result in death during childhood or adolescence. ## Frequency X-linked hyper IgM syndrome is estimated to occur in 2 per million newborn boys. ## Causes Mutations in the CD40LG gene cause X-linked hyper IgM syndrome. This gene provides instructions for making a protein called CD40 ligand, which is found on the surface of immune system cells known as T cells. CD40 ligand attaches like a key in a lock to its receptor protein, which is located on the surface of immune system cells called B cells. B cells are involved in the production of antibodies, and initially they are able to make only IgM antibodies. When CD40 ligand and its receptor protein are connected, they trigger a series of chemical signals that instruct the B cell to start making IgG, IgA, or IgE antibodies. CD40 ligand is also necessary for T cells to interact with other cells of the immune system, and it plays a key role in T cell differentiation (the process by which cells mature to carry out specific functions). Mutations in the CD40LG gene lead to the production of an abnormal CD40 ligand or prevent production of this protein. If CD40 ligand does not attach to its receptor on B cells, these cells cannot produce IgG, IgA, or IgE antibodies. Mutations in the CD40LG gene also impair the T cell's ability to differentiate and interact with other immune system cells. People with X-linked hyper IgM syndrome are more susceptible to infections because they do not have a properly functioning immune system. ### Learn more about the gene associated with X-linked hyper IgM syndrome * CD40LG ## 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. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	X-linked hyper IgM syndrome	c0398689	25,013	medlineplus	https://medlineplus.gov/genetics/condition/x-linked-hyper-igm-syndrome/	2021-01-27T08:25:14	{"gard": ["73"], "mesh": ["D053307"], "omim": ["308230"], "synonyms": []}
A number sign (#) is used with this entry because poor and/or ultrarapid metabolism of several drugs, including debrisoquine, sparteine, nortriptyline, and codeine, is caused by mutation in the cytochrome P450 subfamily IID6 gene (CYP2D6; 124030). Clinical Features Debrisoquine is an adrenergic-blocking medication used for the treatment of hypertension. Oral legend has it that the poor metabolizer phenotype was discovered when the head of the pharmacology unit in England that was testing debrisoquine as an antihypertensive agent collapsed with vascular hypotension on taking a trial dose of the new drug. He was found to be a 'poor metabolizer' (PM), showing greater sensitivity to the antihypertensive effects of the drug (Idle et al., 1978). Mahgoub et al. (1977) found a sharp bimodality in the ratio of urinary debrisoquine to its oxidized metabolite 4-hydroxydebrisoquine in individuals after an oral dose of 10 mg of debrisoquine. About 3% of the study population were poor or nonmetabolizers, and the authors showed that a polymorphism in hydroxylation of the drug was responsible. Family data suggested that the poor metabolizers were homozygous for a recessive gene, although an extensive and systemic family study was not reported. Gonzalez et al. (1988) described 2 phenotypes: poor metabolizers and extensive metabolizers (EM) of debrisoquine. EM individuals, displaying the wildtype phenotype (and presumably genotype), excreted 10 to 200 times more of the urinary metabolite 4-hydroxydebrisoquine than poor metabolizers. The phenotype extended to the metabolism of more than 25 commonly prescribed medications including neuroleptics, antidepressants, and beta-adrenergic blockers (Johansson et al., 1993). Waring et al. (1981) suggested that sulfoxidation of mucodyne may be regulated by the same gene that controls the oxidation of debrisoquine. Poor hydroxylators of debrisoquine also have impaired metabolism of many other drugs such as phenacetin, nortriptyline, phenformin, sparteine, encainide, propranolol, bufuralol, guanoxan, perhexilene, and amitriptyline (Mellstrom et al., 1981; Oates et al., 1982; Inaba et al., 1980; Harmer et al., 1986). Lennard et al. (1982) demonstrated that metabolism of metoprolol, a beta-1-selective adrenoceptor antagonist, exhibited genetic polymorphism of the debrisoquine type. In patients taking the same dose, they found a 17-fold difference in plasma concentrations of metoprolol. Moreover, poor hydroxylators needed only a single daily dose of metoprolol for therapeutic effect, whereas extensive hydroxylators needed 2 or 3 doses a day. Lennard et al. (1983) identified at least 14 other drugs that are metabolized by CYP2D6 including the antiarrhythmic agent propafenone, a sodium-channel blocker with some structural similarity to propranolol. Lee et al. (1990) presented evidence that genetically determined variations in the conversion of propafenone to its 5-hydroxy metabolite accounts for variations in the drug's beta-blocking action. Slow converters (poor metabolizers) showed greater beta-blockade. Gonzalez et al. (1988) showed that poor metabolizers have negligible amounts of the cytochrome P450DB1 protein (CYP2D6). Nebert (1997) estimated that CYP2D6 may be involved in the metabolism of as many as 20% of all commonly prescribed drugs. ### Ultrarapid Metabolizers In addition to deficient hydroxylation of debrisoquine, the opposite phenomenon exists; certain individuals metabolize debrisoquine and several other commonly used drugs very rapidly, resulting in subtherapeutic plasma concentrations at normal doses. Bertilsson et al. (1985, 1993) reported cases in which higher than normal doses of drugs were required to attain therapeutic concentrations. Baumann et al. (1998) reported a patient with depression in whom much higher than usual doses of conventional antidepressants were required. Kawanishi et al. (2002) described a patient with treatment-resistant schizophrenia. Other Features Harmer et al. (1986) found no correlation between the acetylator (see 243400) and the sparteine hydroxylation phenotypes. Barbeau et al. (1985) postulated that Parkinson disease (PD; 168600) is the result of environmental factors acting on genetically susceptible persons against a background of normal aging, and noted that many potential neurotoxic xenobiotics are detoxified by hepatic cytochrome P450. In 40 patients with PD, Barbeau et al. (1985) found that a significant number of patients had partially or totally defective 4-hydroxylation of debrisoquine compared to controls; moreover, poor metabolizers had earlier onset of disease. In a study of 229 patients with Parkinson disease and 720 controls, Smith et al. (1992) found that those with the poor metabolizer phenotype had a 2.54-fold (95% confidence interval 1.51-4.28) increased risk of Parkinson disease. Elbaz et al. (2004) and Deng et al. (2004) presented evidence suggesting that PM are at increased risk for development of PD only when combined with exposure to pesticides. Law et al. (1989), Caporaso et al. (1989, 1990), and Roots et al. (1988) presented data suggesting that extensive metabolizers have an increased risk of lung cancer. Enhanced CYP2D6-mediated metabolism of dietary and environmental agents likely forms reactive intermediates that play a role in cancer initiation and/or promotion in various tissues (Nebert, 1997). Three to 10% of Caucasians are poor metabolizers due to inheritance of 2 defective CYP2D6 alleles, whereas 1 to 2% of Caucasians are ultrarapid metabolizers due to amplification of the CYP2D6 gene. Among 292 long-term heavy smokers, 382 individuals with more variable smoking histories, and 302 never-smokers, Saarikoski et al. (2000) found that the prevalence of ultrarapid metabolizers in heavy smokers (7.9%) was twice that found in individuals with variable smoking habits (3.7%) and 4 times that found in never-smokers (2.0%). The frequency of a poor metabolizer genotype was approximately 2% in each smoker group. The prevalence of poor metabolizer genotype was higher in male never-smokers (3.6%) than in variable smokers (2.7%) and heavy smokers (2.2%). Moreover, a trend test, adjusted by age, gender, and cancer status, revealed a significant trend for increased tobacco usage with increased metabolic capacity. Saarikoski et al. (2000) suggested that increased CYP2D6 activity may contribute to the probability of being addicted to smoking. Inheritance Deficient hydroxylation of debrisoquine and other drugs by CYP2D6 is inherited as an autosomal recessive trait (23:Gonzalez et al., 1988). Although poor metabolizers of sparteine are relatively rare in Japan, Chiba et al. (1988) reported a kindred with autosomal recessive inheritance of the phenotype. Diagnosis The conventional methods of diagnosing the metabolizer phenotype are tests using oral ingestion of debrisoquine (approximately 5 mg) and dextromethorphan (approximately 30 mg). Urine collection, over approximately 5 hours, and analysis yield a metabolic ratio (MR) of the unchanged drug and its oxidized metabolite, i.e., the ratios of debrisoquine-to-4-hydroxydebrisoquine and dextromethorphan-to-dextrorphan. Poor metabolizers are defined by an MR of greater than 12.6 for debrisoquine and an MR of greater than 0.3 for dextromethorphan (Sachse et al., 1997). Ultrarapid metabolizers often have an MR less than 0.1 for debrisoquine (Johansson et al., 1993). Mapping By linkage analysis of individuals with polymorphic sparteine oxidation, Eichelbaum et al. (1987) determined that the gene controlling the phenotype was on chromosome 22q, close to the blood group P1 (111400). Molecular Genetics ### Poor Metabolizers In 20 individuals with poor metabolism of debrisoquine, Gough et al. (1990) identified a splice site mutation in the CYP2D6 gene (124030.0001), yielding a protein with no functional activity. This allele has been termed CYP2D64. In 2 unrelated poor metabolizer individuals, Gough et al. (1990) and Gaedigk et al. (1991) identified a homozygous 11.5-kb deletion associated with deletion of the entire CYP2D6 gene (124030.0002) and total absence of P4502D6 protein in the liver. This allelic variant is also known as CTP2D65. ### Ultrarapid Metabolizers The ultrarapid metabolizer patients reported by Bertilsson et al. (1993), Baumann et al. (1998) and Kawanishi et al. (2002) all had a duplication of the CYP2D6 gene. This mutation resulted in excessive activity of CYP2D6, which metabolizes various commonly used neuroleptics, such as haloperidol, risperidone, thioridazine, and perphenazine. In a family in which 2 sibs and their father had MRs of less than 0.02 (ultrarapid metabolizer phenotype), Johansson et al. (1993) found 12 extra copies of the CYP2D6 gene inherited in an autosomal dominant pattern. In a second family in which 2 sibs had MRs of less than 0.1, the authors found 2 extra copies of the CYP2D6 gene. All affected individuals had a variant CYP2D6 gene, termed CYP2D6L (124030.0007). Gasche et al. (2004) described a patient who had developed life-threatening opioid intoxication after he was given small doses of codeine for the treatment of cough associated with bilateral pneumonia. CYP2D6 genotyping showed 3 or more functioning alleles, as a result of gene duplication (124030.0008), resulting in high levels of morphine and morphine-6 glucuronide. Reduction in CYP3A4 (124010) activity by other medications and acute renal failure causing glucuronide accumulation were also factors in the codeine toxicity. Codeine is ineffective at usual doses in 7 to 10% of the white population because of homozygosity for nonfunctional mutant CYP2D6 alleles (Desmeules et al., 1991). The concentration of O-demethylated metabolites can be as much as 45 times as high in persons with ultrarapid CYP2D6 metabolism as it is in those with poor metabolism (Yue et al., 1997). Population Genetics Evans et al. (1980) estimated the frequency of the poor hydroxylator phenotype to be about 9% in the United Kingdom, but it varies widely among ethnic groups, being about 1% in Arabs and 30% in Hong Kong Chinese (Kalow, 1982). The incidence of poor metabolizers of debrisoquine is between 5 and 10% in the white population of Europe and North America (24:Gonzalez et al., 1988). Zhou et al. (1989) found that Chinese subjects had at least a 2-fold greater sensitivity to the beta-blocking effects of propranolol than white subjects, as measured by the mean plasma concentrations that produced a reduction in heart rate and blood pressure. The Chinese group metabolized propranolol more rapidly than the white group, which resulted in a 76% higher clearance of an oral dose. In addition, the Chinese group had a 45% higher free fraction of propranolol in plasma, which may have contributed somewhat to the increased drug effect. INHERITANCE \- Autosomal recessive NEUROLOGIC Central Nervous System \- Association between poor metabolizers (PM) and Parkinson disease METABOLIC FEATURES \- PMs show impaired metabolism of debrisoquine and related drugs \- PMs show increased sensitivity to effects of medication NEOPLASIA \- Statistical association of extensive metabolism (EM, wildtype) and malignancy, especially smoking-induced lung cancer LABORATORY ABNORMALITIES \- PMs show deficient oxidation of debrisoquine \- PMs show decreased levels of hepatic CYP2D6 enzyme \- PMs excrete 10 to 200 times less metabolite in urine than wildtype (EM) \- PMs have increased metabolic ratio of unchanged drug-to-metabolite in urine MISCELLANEOUS \- CYP2D6 enzyme is located in the endoplasmic reticulum of the liver \- CYP2D6 represents about 1% of total liver cytochrome P450 content \- Ultrarapid metabolizers have multiple copies of the CYP2D6 gene ( 124030.0007 ) MOLECULAR BASIS \- Caused by mutation in the cytochrome P450, subfamily IID6 gene (CYP2D6, 124030.0001 ) ▲ 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	DRUG METABOLISM, POOR, CYP2D6-RELATED	c1837160	25,014	omim	https://www.omim.org/entry/608902	2019-09-22T16:07:00	{"omim": ["608902"]}
Human disease Orf is an exanthemous disease caused by a parapox virus and occurring primarily in sheep and goats. It is also known as contagious pustular dermatitis, contagious ecthyma, infectious labial dermatitis, ecthyma contagiosum, thistle disease[1] and scabby mouth. Orf virus is zoonotic—it can also infect humans.[1] Orf A thumb with two denuded orf lesions, following a bite by a sheep SpecialtyInfectious disease ## Contents * 1 Humans * 2 Other animals * 2.1 Sheep and goats * 3 See also * 4 References * 5 External links ## Humans[edit] Orf is a zoonotic disease, meaning humans can contract this disorder through direct contact with infected sheep and goats or with fomites carrying the orf virus.[2] It causes a purulent-appearing papule locally and generally no systemic symptoms. Infected locations can include the finger, hand, arm, face and even the penis (caused by infection either from contact with the hand during urination or from bestiality). Consequently, it is important to observe good personal hygiene and to wear gloves when treating infected animals.[1] The papule may persist for seven to ten weeks and resolves spontaneously.[citation needed] Orf virus Virus classification (unranked): Virus Realm: Varidnaviria Kingdom: Bamfordvirae Phylum: Nucleocytoviricota Class: Pokkesviricetes Order: Chitovirales Family: Poxviridae Genus: Parapoxvirus Species: Orf virus While orf is usually a benign self-limiting illness which resolves in 3-6 weeks, in the immunocompromised, it can be very progressive and even life-threatening. One percent topical cidofovir has been successfully used in a few patients with progressive disease. Serious damage may be inflicted on the eye if it is infected by orf, even among healthy individuals. The virus can survive in the soil for at least six months.[3] ## Other animals[edit] Orf is primarily a disease of sheep and goats although it has been reported as a natural disease in humans, steenbok and alpacas, chamois and tahrs, reindeer, musk oxen, dogs, cats, mountain goats, bighorn sheep, dall sheep, and red squirrels.[3] ### Sheep and goats[edit] It has been recorded since the late 19th century and has been reported from most sheep-or goat-raising areas, including those in Europe, the Middle East, the United States, Africa, Asia, South America, Canada, New Zealand and Australia.[3] Orf is spread by fomites and direct contact. In some environments, infection is injected by scratches from thistles[1] of both growing and felled plants. Symptoms include papules and pustules on the lips and muzzle, and less commonly in the mouth of young lambs and on the eyelids, feet, and teats of ewes. The lesions progress to thick crusts which may bleed. Orf in the mouths of lambs may prevent suckling and cause weight loss, and can infect the udder of the mother ewe, thus potentially leading to mastitis.[1] Sheep are prone to reinfection.[4] Occasionally the infection can be extensive and persistent if the animal does not produce an immune response.[1] A sheep with orf infection on nose and lips A live virus vaccine (ATCvet code: QI04AD01 (WHO)) is made from scab material and usually given to ewes at the age of two months, but only to lambs when there is an outbreak.[5] The vaccine can cause disease in humans. In sheep and goats, the lesions mostly appear on or near the hairline and elsewhere on the lips and muzzle. In some cases the lesions appear on and in the nostrils, around the eyes, on the thigh, coronet, vulva, udder, and axilla. In rare cases, mostly involving young lambs, lesions are found on the tongue, gums, roof of the mouth and the oesophagus. It has also been reported a number of times to cause lesions in the rumen. In one case it was shown that a severe form of orf virus caused an outbreak involving the gastrointestinal tract, lungs, heart, as well as the buccal cavity, cheeks, tongue and lips. Another severe case was reported pharyngitis, genital lesions and infection of the hooves which led to lameness and, in some cases, sloughing of the hoof.[3] More typically, sheep will become free of orf within a week or so as the disease runs its course. Sheep custodians can assist by ensuring infected lambs receive sufficient milk and separating out the infected stock to slow down cross-transmission to healthy animals. It is advisable for those handling infected animals to wear disposable gloves to prevent cross infection and self-infection. A veterinarian must be contacted if there is a risk of misdiagnosis with other, more serious conditions.[1] ## See also[edit] * Ecthyma * List of cutaneous conditions * List of immunofluorescence findings for autoimmune bullous conditions ## References[edit] 1. ^ a b c d e f g Winter, Agnes; Charmley, Judith (1999). The Sheep Keeper's Veterinary Handbook. Crowood Press Ltd (Marlborough, UK). ISBN 978-1-86126-235-6. 2. ^ "Orf Virus (Sore Mouth Infection)". Centers for Disease Control and Prevention. Retrieved 15 June 2017. 3. ^ a b c d Couch, Alan John (1983). The Development of, and Host Response to, Ovine Contagious Pustular Dermatitis (BS). University of New England, Armidale, N.S.W. doi:10.6084/m9.figshare.96642. 4. ^ Fenner, Frank J.; Gibbs, E. Paul J.; Murphy, Frederick A.; Rott, Rudolph; Studdert, Michael J.; White, David O. (1993). Veterinary Virology (2nd ed.). Academic Press, Inc. ISBN 978-0-12-253056-2. 5. ^ Carter, G.R.; Wise, D.J. (2006). "Poxviridae". A Concise Review of Veterinary Virology. Retrieved 2006-06-13. ## External links[edit] Classification D * ICD-10: B08.0 (ILDS B08.040) * ICD-9-CM: 051.2 * MeSH: D004474 * DiseasesDB: 9262 External resources * eMedicine: article/1133450 Wikimedia Commons has media related to Orf (animal disease). * v * t * e Skin infections, symptoms and signs related to viruses DNA virus Herpesviridae Alpha HSV * Herpes simplex * Herpetic whitlow * Herpes gladiatorum * Herpes simplex keratitis * Herpetic sycosis * Neonatal herpes simplex * Herpes genitalis * Herpes labialis * Eczema herpeticum * Herpetiform esophagitis Herpes B virus * B virus infection VZV * Chickenpox * Herpes zoster * Herpes zoster oticus * Ophthalmic zoster * Disseminated herpes zoster * Zoster-associated pain * Modified varicella-like syndrome Beta * Human herpesvirus 6/Roseolovirus * Exanthema subitum * Roseola vaccinia * Cytomegalic inclusion disease Gamma * KSHV * Kaposi's sarcoma Poxviridae Ortho * Variola * Smallpox * Alastrim * MoxV * Monkeypox * CPXV * Cowpox * VV * Vaccinia * Generalized vaccinia * Eczema vaccinatum * Progressive vaccinia * Buffalopox Para * Farmyard pox: Milker's nodule * Bovine papular stomatitis * Pseudocowpox * Orf * Sealpox Other * Yatapoxvirus: Tanapox * Yaba monkey tumor virus * MCV * Molluscum contagiosum Papillomaviridae HPV * Wart/plantar wart * Heck's disease * Genital wart * giant * Laryngeal papillomatosis * Butcher's wart * Bowenoid papulosis * Epidermodysplasia verruciformis * Verruca plana * Pigmented wart * Verrucae palmares et plantares * BPV * Equine sarcoid Parvoviridae * Parvovirus B19 * Erythema infectiosum * Reticulocytopenia * Papular purpuric gloves and socks syndrome Polyomaviridae * Merkel cell polyomavirus * Merkel cell carcinoma RNA virus Paramyxoviridae * MeV * Measles Togaviridae * Rubella virus * Rubella * Congenital rubella syndrome ("German measles" ) * Alphavirus infection * Chikungunya fever Picornaviridae * CAV * Hand, foot, and mouth disease * Herpangina * FMDV * Foot-and-mouth disease * Boston exanthem disease Ungrouped * Asymmetric periflexural exanthem of childhood * Post-vaccination follicular eruption * Lipschütz ulcer * Eruptive pseudoangiomatosis * Viral-associated trichodysplasia * Gianotti–Crosti 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	Orf (disease)	c0013570	25,015	wikipedia	https://en.wikipedia.org/wiki/Orf_(disease)	2021-01-18T19:01:14	{"mesh": ["D004474"], "umls": ["C0013570"], "wikidata": ["Q681970"]}
Venous lake Venous lake of the lip SpecialtyDermatology A venous lake (also known as "Phlebectasis"[1]) is a generally solitary, soft, compressible, dark blue to violaceous, 0.2- to 1-cm papule commonly found on sun-exposed surfaces of the vermilion border of the lip, face and ears.[2][3][4] Lesions generally occur among the elderly.[5][6] Though these lesions may resemble nodular melanoma, the lack of induration, slow growth, and lightening appearance upon diascopy suggest against it, and indicate a vascular lesion.[7] Additionally, lack of pulsation distinguishes this lesion of the lower lip from a tortuous segment of the inferior labial artery.[4] ## Contents * 1 Cause * 2 Treatment * 3 Images * 4 See also * 5 Footnotes * 6 External links ## Cause[edit] The cause is unknown; however it is thought to be associated with sun exposure, leading to a dilated blood-filled vascular channel[2] "...lined with a singled layer of flattened endothelial cells and a thin wall of fibrous tissue filled with red blood cells."[7] ## Treatment[edit] Treatment may be requested for cosmetic reasons. Traditional techniques such as surgical excision are effective but will leave a scar. Laser therapy has become the mainstay of therapy. Published research suggests that the Long Pulsed Nd:YAG laser is a very effective, with a clearance rate of 94% following a single treatment. In this study no scarring or other complications were reported. [8] ## Images[edit] * Venous lake of the ear * Venous lake of the ear ## See also[edit] * List of cutaneous conditions ## Footnotes[edit] 1. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. Page 588. ISBN 0-7216-2921-0. 2. ^ a b Habif, Thomas P. Clinical Dermatology: A Color Guide to Diagnosis and Therapy. Mosby, Inc. 2004. Page 825. ISBN 0-323-01319-8. 3. ^ Goldberg, LH; Ar, Altman (1985). "Venous lakes of the ears". Cutis. 36 (6): 472–5. PMID 4075841. 4. ^ a b Sauer, Gordon. Manual of Skin Diseases. Lippincott. 1985. Page 315. ISBN 0-397-50668-6. 5. ^ Kuo, HW; Yang, CH. (2003). "Venous lake of the lip treated with a sclerosing agent: report of two cases". Dermatol. Surg. 29 (4): 425–8. doi:10.1046/j.1524-4725.2003.29101.x. PMID 12656828. 6. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 1620. ISBN 1-4160-2999-0. 7. ^ a b Wolff and Johnson. Fitzpatrick's Color Atlas and Synopsis of Clinical Dermatology. The McGraw-Hill Companies. 2005. Page 192. ISBN 0-07-144019-4. 8. ^ Bekhor, Philip (11 Sep 2006). "Long-pulsed Nd:YAG laser treatment of venous lakes: report of a series of 34 cases". Dermatologic Surgery. 32 (9): 1151–4. doi:10.1111/j.1524-4725.2006.32253.x. PMID 16970696. ## External links[edit] Classification D * ICD-10: D18 (ILDS D18.050) * DiseasesDB: 31384 External resources * eMedicine: derm/451 * v * t * e Tumours of blood vessels Blood vessel * Hemangiosarcoma * Blue rubber bleb nevus syndrome * Hemangioendothelioma * Composite * Endovascular papillary * Epithelioid * Kaposiform * Infantile * Retiform) * Spindle cell * Proliferating angioendotheliomatosis * Hemangiopericytoma * Venous lake * Kaposi's sarcoma * African cutaneous * African lymphadenopathic * AIDS-associated * Classic * Immunosuppression-associated * Hemangioblastoma * Hemangioma * Capillary * Cavernous * Glomeruloid * Microvenular * Targeted hemosiderotic * Angioma * Cherry * Seriginosum * Spider * Tufted * Universal angiomatosis * Angiokeratoma * of Mibelli * Angiolipoma * Pyogenic granuloma Lymphatic * Lymphangioma/lymphangiosarcoma * Lymphangioma circumscriptum * Acquired progressive lymphangioma * PEComa * Lymphangioleiomyomatosis * Cystic hygroma * Multifocal lymphangioendotheliomatosis * Lymphangiomatosis Either * Angioma/angiosarcoma * Angiofibroma [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Venous lake	c0948672	25,016	wikipedia	https://en.wikipedia.org/wiki/Venous_lake	2021-01-18T18:58:36	{"umls": ["C0948672"], "icd-10": ["D18"], "wikidata": ["Q7920192"]}
A number sign (#) is used with this entry because of evidence that microcephaly, short stature, and polymicrogyria with or without seizures (MSSP) is caused by homozygous or compound heterozygous mutation in the RTTN gene (610436) on chromosome 18q22. Clinical Features Kheradmand Kia et al. (2012) reported a consanguineous Turkish family in which 2 sibs were demonstrated to have diffuse asymmetric polymicrogyria extending from the frontal to the temporal, parietal, and occipital lobes on brain MRI. Other imaging findings included mild ventricular enlargement and thin or short corpus callosum. One patient had mild cerebellar atrophy. The patients were 12 and 14 years old at the time of the report. Both had microcephaly, moderate to severe mental retardation, poor speech, dysarthria, and seizures. One had pyramidal signs. Another family member had moderate mental retardation and seizures, but detailed clinical features were not available. An unrelated 16-year-old boy with diffuse polymicrogyria had microcephaly, severe mental retardation with lack of speech, seizures, and spastic tetraparesis. Two of the patients had normal abdominal ultrasound with situs solitus; 1 had small kidney volume. Shamseldin et al. (2015) described 3 unrelated families segregating microcephaly, short stature, and polymicrogyria without seizures. In the first family, 3 brothers, born to consanguineous parents from Yemen, had intrauterine growth retardation (IUGR), severe short stature, primary microcephaly, and severe intellectual disability. Brain MRI in the oldest brother, aged 12 years, showed few sulcations, bilateral pachygyria, and shallow Sylvian fissures. He also had a single kidney and mild bilateral hearing loss. His 11-year-old brother had a sacral lesion cephalad to the gluteal crease without abnormality of the spinal cord, a right pelvic ectopic kidney, hypospadias, and an undescended testis. His 6-year-old brother had a sacral lesion cephalad to the gluteal crease. In another family, a 5-year-old male, born to consanguineous Saudi Arabian parents, had severe IGUR, severe short stature, primary microcephaly, mildly delayed motor development, noticeable delay in cognitive and speech development, typical microcephaly-related craniofacial dysmorphism, and increased tone. Brain MRI showed simplified gyration, and a 3D computed tomography scan revealed secondary craniosynostosis. In the third family, 2 Canadian brothers were affected. One boy had severe microcephaly, a sloping forehead, a high and broad nasal bridge, multiple joint contractures, and severe failure to thrive. MRI showed severe cerebral and cerebellar hypoplasia, incomplete separation of the cerebral hemispheres, dysgenesis of the corpus callosum, an abnormal ventricular system, a large posterior cyst, multiple areas of lissencephaly and/or pachygyria and polymicrogyria, and multiple subependymal gray matter heterotopias. He died at 2 months of age of a cardiorespiratory arrest. His brother had severe, prenatal-onset growth restriction characterized by microcephaly, and a sloping forehead. His MRI showed microcephaly with gross brain parenchymal abnormalities affecting the cerebral hemispheres and the cerebellum, both of which were extremely small, agenesis of the corpus callosum, reduced sulcation, deformed ventricles, and large cerebrospinal fluid intensity areas occupying the majority of supratentorial compartments bilaterally. He also had cryptorchidism and required urgent surgical intervention for duodenal atresia. He died at 19 days of age. Grandone et al. (2016) reported a brother and sister, born of first-cousin Moroccan parents, with MSSP. At birth, the sibs had severe microcephaly, 28 cm (-5.5 SD) in the boy and 27 cm (-5.3 SD) in the girl. Birth weights and lengths were -1.47 SD and -2.3 SD in the boy and -1.7 SD and -2.9 SD in the girl, respectively. Both sibs presented with diffuse eczema at birth. Facial dysmorphisms included receding forehead and chin, protruding nose, hypotelorism with prominent eyes, slightly upturned palpebral fissures, and simple helices. Both sibs showed severe growth failure and developmental delay. The boy started to walk at age 20 months and speech was absent at his last examination at age 35 months; the girl could sit and crawl at 21 months but could not yet walk and had no speech. Skin remained diffusely pruritic, scaled, and dry in both patients, but dermatitis had begun to improve spontaneously in the boy. Brain MRI showed lissencephaly, periventricular gray matter heterotopia, pons hypoplasia, and a quadigeminal cistern arachnoid cyst extending into the right occipital region. Wambach et al. (2018) identified a boy with primary microcephaly, simplified gyri, pontocerebellar hypoplasia, contractures, and intractable epilepsy. The boy had a head circumference within normal limits (-1.5 SD) at birth, but by 6 weeks of age, he was severely microcephalic (-4.9 SD). On physical exam, he had microcephaly with metopic ridging, occipital prominence, bilateral microphthalmia, microstomia, microretrognathia, smooth philtrum, relatively large cupped low-set ears, bilateral contractures of knees and ankles, mild camptodactyly with contractures of the interphalangeal joints, and bilateral syndactyly of fourth and fifth fingers and second to fifth toes, microphallus, cryptorchidism, and appendicular hypertonia with normal deep tendon reflexes. Brain MRI showed cerebral hypoplasia with simplified gyral pattern, pontocerebellar hypoplasia, bilateral frontal cortical dysplasia, agenesis of the corpus callosum, thinning of the periventricular white matter, misshapen orbital globes, and optic nerve hypoplasia. Ophthalmologic evaluation showed rudimentary retinal vasculature, hypoplastic optic nerves, and pale optic discs. The patient also had gracile appearing bones with thin ribs on skeletal survey. He had bilateral pyelocaliectasis on renal ultrasound. He had intractable seizures and died at age 4 months of acute, progressive respiratory failure. Wambach et al. (2018) noted that this patient's ophthalmologic and skeletal findings had not previously been reported in patients with MSSP. Cavallin et al. (2018) reported a boy with severe microcephaly, polymicrogyria, and growth restriction, consistent with MSSP. Concerns were initially raised prenatally because of a small head circumference (-4.5 SD) and other abnormalities of the brain. Birth length and weight were also abnormal (-4 SD and -2 SD, respectively). The boy showed microcephaly-related craniofacial dysmorphism, axial hypotonia, and limb spasticity. He began to develop hyperkinesia, with agitation and crying, and severe sleep disorders by the age of 6 months. At last evaluation at age 5 years 9 months, his height and weight were both -4 SD and his head circumference was -10 SD. Development was severely delayed. He had hyperkinetic movement disorders, with self-injurious behavior and motor stereotypies. Neurologic examination showed pyramidal signs. Brain MRI showed microcephaly with extremely reduced frontal lobes, bilateral generalized dysgyria with areas of polymicrogyria, and posterior corpus callosum agenesis. The patient did not develop seizures. EEG showed a rapid alpha-like rhythm with frontotemporal spikes. Inheritance The transmission pattern of polymicrogyria in the family reported by Kheradmand Kia et al. (2012) was consistent with autosomal recessive inheritance. Mapping By autozygosity mapping on the basis of a while-genome search of 3 affected members of a family segregating polymicrogyria with seizures, Kheradmand Kia et al. (2012) found shared homozygous regions on chromosomes 14q24.3-q31.1 and 18q22. Molecular Genetics In 3 members of a consanguineous Turkish family with polymicrogyria with seizures, Kheradmand Kia et al. (2012) identified a homozygous mutation in the RTTN gene (L932F; 610436.0001). The mutation was identified by autozygosity mapping followed by candidate gene sequencing. Another unrelated patient with a similar disorder carried a different homozygous mutation (C27Y; 610436.0002). Mutant L932F RTTN correctly localized to the basal bodies in patient fibroblasts, but there was a higher percentage of ciliary abnormalities, including short cilia with bulbous tips, compared to control. No ciliary abnormalities were apparent in cells from the patient with the C27Y mutation. However, gene expression profiling in patient fibroblasts with both mutations showed deregulation of several genes involved in brain development and/or known to be regulated at the cilium compared to control fibroblasts. Such genes included SHH (600725), HHIP (606178), WNT5A (164975), and BMP4 (112262). The polymicrogyria was primarily a postmigratory cortical organization defect, consistent with the localization of rotatin to the marginal zone in mouse embryonic brain. The findings supported the involvement of rotatin in the pathogenesis of this cortical malformation, and suggested that aberrant ciliary function contributes to abnormal development and organization of the cortex in humans. In affected members of 3 unrelated families with microcephaly, short stature, and polymicrogyria, Shamseldin et al. (2015) identified homozygous or compound heterozygous mutations in the RTTN gene (610436.0003-610436.0006). In a brother and sister, born of first-cousin Moroccan parents, with MSSP, Grandone et al. (2016) identified a homozygous missense mutation in the RTTN gene (R985G; 610436.0007). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and was not found in the gnomAD database. Using trio-based whole-exome sequencing, Cavallin et al. (2018) identified homozygosity for the R985G mutation in the RTTN gene in a boy with MSSP. The boy's consanguineous Moroccan parents were heterozygous for the mutation. In a male infant with MSSP, Wambach et al. (2018) identified compound heterozygous mutations in the RTTN gene: V64F, which was not present in the ExAC database, and an intronic variant (c.32-3C-T), which was present at a frequency of 0.0073 in the ExAC database. Cultured fibroblasts from the infant showed abnormal cilia with reduced length and number of primary cilia. The authors suggested that functional characterization of primary cilia length and number could be used to determine RTTN variant pathogenicity. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature, mild HEAD & NECK Head \- Microcephaly, mild to severe (up to -10 SD) Eyes \- Microphthalmia (1 patient) \- Rudimentary retinal vasculature (1 patient) \- Hypoplastic optic nerves (1 patient) Mouth \- Microstomia CHEST Ribs Sternum Clavicles & Scapulae \- Thin ribs ABDOMEN \- Situs solitus GENITOURINARY Kidneys \- Decreased kidney volume (1 patient) \- Pyelocaliectasis, bilateral (1 patient) SKELETAL \- Gracile bones NEUROLOGIC Central Nervous System \- Mental retardation, moderate to severe \- Lack of speech or poor speech \- Dysarthria \- Seizures \- Pyramidal signs (in some patients) \- Spasticity (in some patients) \- Abnormal EEG \- Polymicrogyria, diffuse, asymmetric \- Abnormal corpus callosum \- Cerebellar atrophy, mild (1 patient) MISCELLANEOUS \- Variable features may be present \- Two unrelated families have been reported (last curated September 2012) MOLECULAR BASIS \- Caused by mutation in the rotatin gene (RTTN, 610436.0001 ) ▲ 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	MICROCEPHALY, SHORT STATURE, AND POLYMICROGYRIA WITH OR WITHOUT SEIZURES	c3553831	25,017	omim	https://www.omim.org/entry/614833	2019-09-22T15:54:06	{"omim": ["614833"], "orphanet": ["468631"], "synonyms": ["Alternative titles", "POLYMICROGYRIA WITH SEIZURES"]}
A number sign (#) is used with this entry because of evidence that intellectual developmental disorder with hypertelorism and distinctive facies (IDDHDF) is caused by heterozygous mutation in the CCNK gene (603544) on chromosome 14q32. One such patient has been reported. Clinical Features Fan et al. (2018) reported a 13-year-old African American girl (patient 4) with moderately impaired intellectual development, mildly delayed fine and gross motor skills, and delayed speech. She had dysmorphic features, including a high hairline, hypertelorism, abnormal palpebral fissures, thin eyebrows, low-set posteriorly rotated ears, broad nasal bridge and tip, thin upper lip, and narrow jaw. She also had generalized overgrowth, macrocephaly, tapered fingers, flat feet, and fifth finger clinodactyly. Cytogenetics Fan et al. (2018) reported 3 unrelated Chinese children (patients 1, 2, and 3) with an intellectual developmental disorder associated with de novo heterozygous deletions on chromosome 14q32.3. The deletions ranged from 317 to 2,440 kb with no common breakpoints, and included multiple genes. The smallest region of overlap included the CCNK gene, which was considered to be the prioritized candidate for the phenotype. The patients had severe to profound global developmental delay with poor or absent speech, poor fine and gross motor skills, and common facial features, such as high hairline, hypertelorism, thin eyebrows, dysmorphic ears, small palpebral fissures, broad nasal bridge and tip, thick nasal alae, long philtrum, thin upper vermilion, and narrow jaw. Two patients had generalized overgrowth and 2 had autistic features, mainly stereotypic movements and behaviors. Cells derived from 2 of the patients showed about a 50% reduction in CCNK mRNA, consistent with a dosage effect of genomic copy number loss. A search of the Decipher database identified 5 additional individuals with large deletions encompassing the CCNK gene; these patients had overlapping features, including developmental delay/intellectual disability and dysmorphic facial features. Molecular Genetics In a 13-year-old African American girl (patient 4) with IDDHDF, Fan et al. (2018) identified a de novo heterozygous missense mutation in the CCNK gene (K111E; 603544.0001). The mutation was found by whole-exome sequencing. Patient cells were not available for study, but the authors postulated that the mutation could cause steric hindrance and lead to instability of the complex. Expression of the mutation failed to rescue the abnormal phenotype of zebrafish with knockdown of the ccnk gene. Fan et al. (2018) suggested haploinsufficiency as a pathogenetic mechanism. Animal Model Blazek et al. (2011) found that knockout of Cyck in mice resulted in early embryonic lethality, since no Cyck -/- embryos were obtained at embryonic day 4.5. Cyck +/- mice appeared normal and were fertile. LacZ staining showed widespread Cyck expression during mouse embryonic development. Fan et al. (2018) found wide expression of the ccnk gene in developing zebrafish at 1 day postfertilization, followed by continuous expression in the brain throughout development. Morpholino knockdown or CRISPR/Cas9-based knockout of the ccnk gene resulted in dose-dependent embryonic lethality, as well as small eyes, deformed head, cartilage jaw abnormalities, and curly spinal cord, suggesting a role in the central nervous system. There was also evidence for increased neural cell death in mutant animals. INHERITANCE \- Autosomal dominant GROWTH Other \- Overgrowth, generalized HEAD & NECK Head \- Macrocephaly, mild Face \- Narrow jaw \- High anterior hairline \- Long philtrum Ears \- Low-set ears \- Posteriorly rotated ears \- Dysmorphic ears Eyes \- Hypertelorism \- Thin eyebrows \- Long palpebral fissures \- Abnormal palpebral fissures Nose \- Broad nasal bridge \- Broad nasal tip \- Thick nasal alae Mouth \- Thin upper vermilion SKELETAL Hands \- Tapered fingers Feet \- Flat feet NEUROLOGIC Central Nervous System \- Global developmental delay \- Impaired intellectual development \- Poor or absent speech \- Delayed fine and gross motor skills MISCELLANEOUS \- One patient with a confirmed mutation in the CCNK gene has been reported (last curated October 2018) \- Some patients with similar features have a larger deletion involving several genes, including CCNK MOLECULAR BASIS \- Caused by mutation in the cyclin K gene (CCNK, 603544.0001 ) ▲ 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	INTELLECTUAL DEVELOPMENTAL DISORDER WITH HYPERTELORISM AND DISTINCTIVE FACIES	None	25,018	omim	https://www.omim.org/entry/618147	2019-09-22T15:43:22	{"omim": ["618147"]}
Say et al. (1973) described a brother and sister, born of healthy but consanguineous parents, who had triangular facies, malocclusion ('open bite'), and short stature. The girl was 146 cm tall at age 14 and the boy 107 cm tall at age 6. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	MALOCCLUSION AND SHORT STATURE	c1855453	25,019	omim	https://www.omim.org/entry/248350	2019-09-22T16:25:39	{"mesh": ["C565421"], "omim": ["248350"]}
A number sign (#) is used with this entry because of evidence that nonsyndromic congenital nail disorder-10 (NDNC10) can be caused by homozygous mutation in the FZD6 gene (603409) on chromosome 8q22.3-q23.1. Description Nonsyndromic congenital nail disorder-10 is characterized by onychauxis (thick nails), hyponychia, and onycholysis of all nails, with claw-shaped fingernails in some individuals (summary by Frojmark et al., 2011). For a list of other nonsyndromic congenital nail disorders and a discussion of genetic heterogeneity, see NDNC1 (161050). Clinical Features Frojmark et al. (2011) examined 4 affected individuals from 2 unrelated consanguineous Pakistani families segregating autosomal recessive isolated nail dysplasia. Affected members from one of the families had more severe nail dystrophy than affected individuals from the other family, but all showed a variable degree of onychauxis, hyponychia, and onycholysis of fingernails and toenails, with the fingernails having a claw-like appearance. No other disorders or anomalies of ectodermal tissues, including hair, teeth, sweat glands, or skin, were noted, and individuals with dysplastic nails had normal hearing and normal psychomotor development. Mapping In 1 of 2 consanguineous Pakistani families segregating autosomal recessive isolated nail dysplasia, Frojmark et al. (2011) performed autozygosity mapping and detected 1 large homozygous region spanning 17 Mb on chromosome 8q. Within this region, affected members of the other Pakistani family were homozygous over 800 kb. Linkage analysis using polymorphic microsatellite markers yielded a maximum cumulative 2-point lod score of 3.87 (theta = 0). Each family had a distinctive haplotype. Inheritance Nonsyndromic congenital nail disorder-10 is an autosomal recessive disorder (Frojmark et al., 2011). Molecular Genetics In 2 unrelated consanguineous Pakistani families segregating autosomal recessive isolated nail dysplasia mapping to 8q, Frojmark et al. (2011) analyzed the candidate gene FZD6 and identified homozygosity for a nonsense (603409.0001) and a missense (603409.0002) mutation in affected members of each family, respectively. Frojmark et al. (2011) noted that affected individuals in both families retained regenerative capacity of the nail plate, suggesting that the nail matrix was intact; thus, the primary defect associated with FZD6 mutations seemed to be related to perturbed formation and attachment of the nail plate (onycholysis). INHERITANCE \- Autosomal recessive SKIN, NAILS, & HAIR Nails \- Onychauxis (thickening) \- Onycholysis \- Hyponychia \- Claw-like appearance of fingernails MOLECULAR BASIS \- Caused by mutation in the homolog of Drosophila frizzled-6 gene (FZD6, 603409.0001 ) ▲ 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	NAIL DISORDER, NONSYNDROMIC CONGENITAL, 10	c3279974	25,020	omim	https://www.omim.org/entry/614157	2019-09-22T15:56:23	{"doid": ["0080088"], "omim": ["614157"], "orphanet": ["280654"], "synonyms": ["CLAW-SHAPED NAILS", "ONYCHAUXIS, HYPONYCHIA, AND ONYCHOLYSIS", "Alternative titles"]}
Annular lichen planus (LP) is a rare form of lichen planus, which is a condition that affects the skin and/or mouth. In annular LP, specifically, affected people develop ring-shaped, slightly raised, purple lesions with no central atrophy (tissue breakdown). Purely annular LP is very rare; however, annular lesions occur in approximately 10% of all cases of lichen planus. The exact underlying cause of annular LP is unknown. Treatment is not always necessary as some cases of annular LP resolve on their own. Mild cases can often be managed with topical steroids, while more intensive therapies may be required for severe 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	Annular lichen planus	c0406363	25,021	gard	https://rarediseases.info.nih.gov/diseases/12674/annular-lichen-planus	2021-01-18T18:02:05	{"umls": ["C0406363"], "orphanet": ["254424"], "synonyms": ["Annular LP"]}
Neuropsychological disorder caused by damage to the inferior parietal lobule Not to be confused with Gerstmann–Sträussler–Scheinker syndrome, which is a transmissible spongiform encephalopathy. Gerstmann syndrome The inferior parietal lobule, with damage in this area most often associated with Gerstmann syndrome SpecialtyNeurology, neuropsychology SymptomsDysgraphia, dyscalculia, finger agnosia, left-right disorientation, constructional apraxia, aphasia CausesIdiopathic, stroke, dementia Gerstmann syndrome is a neuropsychological disorder that is characterized by a constellation of symptoms that suggests the presence of a lesion usually near the junction of the temporal and parietal lobes at or near the angular gyrus. Gerstmann syndrome is typically associated with damage to the inferior parietal lobule of the dominant hemisphere. It is classically considered a left-hemisphere disorder, although right-hemisphere damage has also been associated with components of the syndrome.[1] It is named after Jewish Austrian-born American neurologist Josef Gerstmann.[2] ## Contents * 1 Symptoms * 2 Causes * 2.1 In adults * 2.2 In children * 3 Diagnosis * 4 Treatment * 5 Prognosis * 6 References * 7 Further reading * 8 External links ## Symptoms[edit] Gerstmann syndrome is characterized by four primary symptoms, collectively referred to as a tetrad: 1. Dysgraphia/agraphia: deficiency in the ability to write[3][4] 2. Dyscalculia/acalculia: difficulty in learning or comprehending mathematics[3][4] 3. Finger agnosia: inability to distinguish the fingers on the hand[3][4] 4. Left-right disorientation[3][4] ## Causes[edit] This disorder is often associated with brain lesions in the dominant (usually left) hemisphere including the angular and supramarginal gyri (Brodmann area 39 and 40 respectively) near the temporal and parietal lobe junction. There is significant debate in the scientific literature as to whether Gerstmann syndrome truly represents a unified, theoretically motivated syndrome. Thus its diagnostic utility has been questioned by neurologists and neuropsychologists alike. The angular gyrus is generally involved in translating visual patterns of letters and words into meaningful information, such as is done while reading.[citation needed] ### In adults[edit] In adults, the syndrome may occur after a stroke.[4] In addition to exhibiting the above symptoms, many adults also experience dysphasia or aphasia,[1] which is difficulty in expressing oneself when speaking, in understanding speech, or in reading and writing.[citation needed] ### In children[edit] There are few reports of the syndrome, sometimes called developmental Gerstmann syndrome, in children.[5] The cause is not known. Most cases are identified when children reach school age, a time when they are challenged with writing and mathematic exercises. Generally, children with the disorder exhibit poor handwriting and spelling skills, and difficulty with math functions, including adding, subtracting, multiplying, and dividing. An inability to differentiate right from left and to discriminate among individual fingers may also be apparent. In addition to the four primary symptoms, many children also suffer from constructional apraxia, an inability to copy simple drawings. Frequently, there is also an impairment in reading. Children at any level of intelligence may be affected with the disorder.[5] ## Diagnosis[edit] Diagnosis may be clinical if associated with dementia and other etiologies. In cases caused by stroke, MRI will show a corresponding stroke in the inferior parietal lobule. In the acute stage, this will be bright (restricted diffusion) on the DWI sequence and dark at the corresponding area on the ADC sequence.[vague] ## Treatment[edit] There is no cure for Gerstmann syndrome. Treatment is symptomatic and supportive. Occupational and speech therapies may help diminish the dysgraphia and apraxia. In addition, calculators and word processors may help school children cope with the symptoms of the disorder.[citation needed] ## Prognosis[edit] In adults, many of the symptoms diminish over time. Although it has been suggested that a similar diminishing of symptoms occurs in children as well, it appears more likely that most do not overcome their deficits, but instead simply learn to adjust.[6] ## References[edit] 1. ^ a b Heimburger, Robert; Demyer, William; Reitan, Ralph (1964). "Implications of Gerstmann's syndrome". J. Neurol. Neurosurg. Psychiat. 27 (7): 52–7. PMC 495679. 2. ^ synd/2267 at Who Named It? 3. ^ a b c d Vallar G (July 2007). "Spatial neglect, Balint-Homes' and Gerstmann's syndrome, and other spatial disorders". CNS Spectr. 12 (7): 527–36. doi:10.1017/S1092852900021271. PMID 17603404. 4. ^ a b c d e Carota A, Di Pietro M, Ptak R, Poglia D, Schnider A (2004). "Defective spatial imagery with pure Gerstmann's syndrome". Eur. Neurol. 52 (1): 1–6. doi:10.1159/000079251. PMID 15218337. 5. ^ a b Miller CJ, Hynd GW (April 2004). "What ever happened to developmental Gerstmann's syndrome? Links to other pediatric, genetic, and neurodevelopmental syndromes". J. Child Neurol. 19 (4): 282–9. doi:10.1177/088307380401900408. PMID 15163095. 6. ^ "Archived copy". Archived from the original on 2012-06-24. Retrieved 2012-06-27.CS1 maint: archived copy as title (link) ## Further reading[edit] * Ardila A, Rosselli M (December 2002). "Acalculia and dyscalculia" (PDF). Neuropsychol Rev. 12 (4): 179–231. doi:10.1023/a:1021343508573. PMID 12539968. * "Gerstmann's Syndrome Information Page". National Institute of Neurological Disorders and Stroke (NINDS). * Reeve R, Humberstone J (2011). "Five- to 7-year-olds' finger gnosia and calculation abilities". Front Psychol. 2: 359. doi:10.3389/fpsyg.2011.00359. PMC 3236444. PMID 22171220. ## External links[edit] Classification D * ICD-10: F81.2 * ICD-9-CM: 784.69 * MeSH: D005862 * DiseasesDB: 30728 External resources * Orphanet: 221117 * v * t * e Mental and behavioral disorders Adult personality and behavior Gender dysphoria * Ego-dystonic sexual orientation * Paraphilia * Fetishism * Voyeurism * Sexual maturation disorder * Sexual relationship disorder Other * Factitious disorder * Munchausen syndrome * Intermittent explosive disorder * Dermatillomania * Kleptomania * Pyromania * Trichotillomania * Personality disorder Childhood and learning Emotional and behavioral * ADHD * Conduct disorder * ODD * Emotional and behavioral disorders * Separation anxiety disorder * Movement disorders * Stereotypic * Social functioning * DAD * RAD * Selective mutism * Speech * Stuttering * Cluttering * Tic disorder * Tourette syndrome Intellectual disability * X-linked intellectual disability * Lujan–Fryns syndrome Psychological development (developmental disabilities) * Pervasive * Specific Mood (affective) * Bipolar * Bipolar I * Bipolar II * Bipolar NOS * Cyclothymia * Depression * Atypical depression * Dysthymia * Major depressive disorder * Melancholic depression * Seasonal affective disorder * Mania Neurological and symptomatic Autism spectrum * Autism * Asperger syndrome * High-functioning autism * PDD-NOS * Savant syndrome Dementia * AIDS dementia complex * Alzheimer's disease * Creutzfeldt–Jakob disease * Frontotemporal dementia * Huntington's disease * Mild cognitive impairment * Parkinson's disease * Pick's disease * Sundowning * Vascular dementia * Wandering Other * Delirium * Organic brain syndrome * Post-concussion syndrome Neurotic, stress-related and somatoform Adjustment * Adjustment disorder with depressed mood Anxiety Phobia * Agoraphobia * Social anxiety * Social phobia * Anthropophobia * Specific social phobia * Specific phobia * Claustrophobia Other * Generalized anxiety disorder * OCD * Panic attack * Panic disorder * Stress * Acute stress reaction * PTSD Dissociative * Depersonalization disorder * Dissociative identity disorder * Fugue state * Psychogenic amnesia Somatic symptom * Body dysmorphic disorder * Conversion disorder * Ganser syndrome * Globus pharyngis * Psychogenic non-epileptic seizures * False pregnancy * Hypochondriasis * Mass psychogenic illness * Nosophobia * Psychogenic pain * Somatization disorder Physiological and physical behavior Eating * Anorexia nervosa * Bulimia nervosa * Rumination syndrome * Other specified feeding or eating disorder Nonorganic sleep * Hypersomnia * Insomnia * Parasomnia * Night terror * Nightmare * REM sleep behavior disorder Postnatal * Postpartum depression * Postpartum psychosis Sexual dysfunction Arousal * Erectile dysfunction * Female sexual arousal disorder Desire * Hypersexuality * Hypoactive sexual desire disorder Orgasm * Anorgasmia * Delayed ejaculation * Premature ejaculation * Sexual anhedonia Pain * Nonorganic dyspareunia * Nonorganic vaginismus Psychoactive substances, substance abuse and substance-related * Drug overdose * Intoxication * Physical dependence * Rebound effect * Stimulant psychosis * Substance dependence * Withdrawal Schizophrenia, schizotypal and delusional Delusional * Delusional disorder * Folie à deux Psychosis and schizophrenia-like * Brief reactive psychosis * Schizoaffective disorder * Schizophreniform disorder Schizophrenia * Childhood schizophrenia * Disorganized (hebephrenic) schizophrenia * Paranoid schizophrenia * Pseudoneurotic schizophrenia * Simple-type schizophrenia Other * Catatonia Symptoms and uncategorized * Impulse control disorder * Klüver–Bucy syndrome * Psychomotor agitation * Stereotypy * v * t * e Symptoms, signs and syndromes associated with lesions of the brain and brainstem Brainstem Medulla (CN 8, 9, 10, 12) * Lateral medullary syndrome/Wallenberg * PICA * Medial medullary syndrome/Dejerine * ASA Pons (CN 5, 6, 7, 8) * Upper dorsal pontine syndrome/Raymond-Céstan syndrome * Lateral pontine syndrome (AICA) (lateral) * Medial pontine syndrome/Millard–Gubler syndrome/Foville's syndrome (basilar) * Locked-in syndrome * Internuclear ophthalmoplegia * One and a half syndrome Midbrain (CN 3, 4) * Weber's syndrome * ventral peduncle, PCA * Benedikt syndrome * ventral tegmentum, PCA * Parinaud's syndrome * dorsal, tumor * Claude's syndrome Other * Alternating hemiplegia Cerebellum * Latearl * Dysmetria * Dysdiadochokinesia * Intention tremor) * Medial * Cerebellar ataxia Basal ganglia * Chorea * Dystonia * Parkinson's disease Cortex * ACA syndrome * MCA syndrome * PCA syndrome * Frontal lobe * Expressive aphasia * Abulia * Parietal lobe * Receptive aphasia * Hemispatial neglect * Gerstmann syndrome * Astereognosis * Occipital lobe * Bálint's syndrome * Cortical blindness * Pure alexia * Temporal lobe * Cortical deafness * Prosopagnosia Thalamus * Thalamic syndrome Other * Upper motor neuron lesion * Aphasia * v * t * e Dyslexia and related specific developmental disorders Conditions Speech, language, and communication * Expressive language disorder * Infantile speech * Landau–Kleffner syndrome * Language disorder * Lisp * Mixed receptive-expressive language disorder * Specific language impairment * Speech and language impairment * Speech disorder * Speech error * Speech sound disorder * Stuttering * Tip of the tongue Learning disability * Dyslexia * Dyscalculia * Dysgraphia * Disorder of written expression Motor * Developmental coordination disorder * Developmental verbal dyspraxia Sensory * Auditory processing disorder * Sensory processing disorder Related topics * Dyslexia research * Irlen filters * Learning Ally * Learning problems in childhood cancer * Literacy * Management of dyslexia * Multisensory integration * Neuropsychology * Reading acquisition * Spelling * Writing system Lists * Dyslexia in fiction * Languages by Writing System * People with dyslexia [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Gerstmann syndrome	c0017494	25,022	wikipedia	https://en.wikipedia.org/wiki/Gerstmann_syndrome	2021-01-18T18:55:49	{"gard": ["8660"], "mesh": ["D005862"], "umls": ["C0017494"], "orphanet": ["221117"], "wikidata": ["Q1515119"]}
A number sign (#) is used with this entry because of evidence that lethal congenital contracture syndrome-9 (LCCS9) is caused by homozygous mutation in the GPR126 gene (ADGRG6; 612243) on chromosome 6q24. For a general phenotypic description and discussion of genetic heterogeneity of lethal congenital contracture syndrome, see LCCS1 (253310). Clinical Features Ravenscroft et al. (2015) reported 4 affected individuals from 3 unrelated consanguineous families with severe arthrogryposis multiplex congenita. In the first family, prenatal ultrasound at 20 weeks of gestation showed distal joint contractures, diaphragmatic defect, and reduced fetal mobility. The pregnancy was terminated, and fetopathologic examination revealed joint retractions associated with pterygium at the right elbow and axilla, as well as thin and elevated diaphragmatic cupolae. In the second family, which was of Portuguese ancestry, prenatal ultrasound at 16 weeks of gestation showed upper limb arthrogryposis, and 8 weeks later, micrognathia and polyhydramnios were also observed. MRI at 25 weeks of gestation revealed micrognathia, fixed extension of the arms, and flexion of the elbows, wrists, and hands; at 28 weeks, intrauterine growth retardation (IUGR) became evident. The female infant was born at 31 weeks by cesarean section after premature amniorrhexis; examination revealed ocular hypertelorism, upper limb arthrogryposis with ulnar deviation of hands, camptodactyly, sparse dermal ridges, ankylosis of the knee joint, and talipes equinovarus. She underwent cardiopulmonary resuscitation and orotracheal intubation, but developed severe pulmonary hypertension and died from cardiorespiratory arrest 1 hour after birth. In the third family, of Iraqi descent, the first pregnancy was complicated by polyhydramnios requiring drainage. Antenatal ultrasound at 30 weeks of gestation showed IUGR, possible talipes equinovarus, and no upper limb movements for over 1 hour. The female infant was delivered by emergency cesarean section at 36 weeks because of severe preeclampsia, and died of respiratory failure at 1 hour of life. Severe arthrogryposis of large and small joints was noted, with adducted thumbs, ulnar deviation, fixed flexion contractures of the hands and wrists, reduced digital creases, severe talipes equinovarus, and generally reduced muscle bulk in the limbs. Dysmorphic facial features included triangular face, low-set ears, depressed nasal bridge, anteverted nares, thin upper lip, and micrognathia. Autopsy confirmed short umbilical cord and pulmonary hypoplasia. A second affected pregnancy in this family was terminated at 19 weeks of gestation after ultrasound at 18 weeks showed bilateral talipes equinovarus, contractures of upper limbs, and no movement of the arms for over 1 hour. Examination revealed a male fetus with arthrogryposis and poorly developed musculature of the limbs, as well as subtle dysmorphic features, including low-set ears and micrognathia. 'Babygram' x-ray in the female infant showed thoracic kyphoscoliosis but no structural abnormalities, whereas multiple segmentation abnormalities of the thoracic spine were seen in the male fetus. Histologic examination of muscle biopsies from the 2 sibs was consistent with diffuse nonspecific myopathy, showing significant variability in muscle-fiber diameter within each muscle sampled, with predominantly normal and atrophic small fibers, but occasional large hypertrophic fibers. Both type 1 and type 2 fibers appeared atrophic on skeletal muscle myosin staining, and the most severely affected muscle was the diaphragm. Analysis of peripheral nerves demonstrated absence of myelin basic protein (MBP; 159430), suggesting that the disease is due to defective myelination of the peripheral axons during fetal development. Molecular Genetics By targeted exome sequencing on a DNA sample from a fetus with lethal arthrogryposis, Ravenscroft et al. (2015) identified a homozygous nonsense mutation in the GPR126 gene (R7X; 612243.0001) for which the unaffected first-cousin parents were heterozygous. Exome sequencing of a similarly affected proband from a consanguineous family of Portuguese ancestry revealed homozygosity for a duplication in GPR126 (612243.0002), which was present in heterozygosity in the unaffected first-cousin parents. In a consanguineous family of Iraqi descent, the proband and an affected sib were both homozygous for a GPR126 Ravenscroft et al. (2015) identified homozygosity for a missense mutation (V741E; 612243.0003) that was found in heterozygosity in their unaffected second-cousin parents. INHERITANCE \- Autosomal recessive GROWTH Other \- Intrauterine growth retardation HEAD & NECK Face \- Triangular face \- Micrognathia Ears \- Low-set ears Eyes \- Hypertelorism Nose \- Depressed nasal bridge \- Anteverted nares Mouth \- Thin upper lip RESPIRATORY Lung \- Pulmonary hypoplasia CHEST Diaphragm \- Diaphragmatic atrophy \- Diaphragmatic defect (rare) SKELETAL Spine \- Scoliosis (rare) \- Segmentation anomalies (rare) Limbs \- Flexion contractures of wrists \- Flexion contractures of elbows \- Extension contractures of elbows (rare) \- Extension contracture of arms (rare) \- Ankylosis of knee joint Hands \- Ulnar deviation of hands \- Flexion contractures of fingers \- Adducted thumbs Feet \- Talipes equinovarus \- Talus valgus (rare) SKIN, NAILS, & HAIR Skin \- Pterygium of axilla (rare) \- Pterygium of elbow (rare) \- Reduced digital creases (rare) \- Sparse dermal ridges (rare) MUSCLE, SOFT TISSUES \- Reduced muscle bulk \- Nonspecific myopathy seen on biopsy \- Variation in skeletal muscle fiber diameter \- Atrophic skeletal muscle fibers on myosin staining PRENATAL MANIFESTATIONS Movement \- Decreased fetal movements Amniotic Fluid \- Polyhydramnios \- Premature amniorrhexis (in some pregnancies) Placenta & Umbilical Cord \- Short umbilical cord (rare) Maternal \- Severe preeclampsia (in some pregnancies) MISCELLANEOUS \- Variable phenotype \- Affected individuals die soon after birth due to respiratory failure MOLECULAR BASIS \- Caused by mutation in the G protein-coupled receptor-126 gene (GPR126, 612243.0001 ) ▲ 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	LETHAL CONGENITAL CONTRACTURE SYNDROME 9	c4225303	25,023	omim	https://www.omim.org/entry/616503	2019-09-22T15:48:40	{"omim": ["616503"]}
Reeves (1967) reported 2 families, each with multiple affected persons in 3 generations. Generalized joint laxity was not present. Although Reeves favored X-linked dominant inheritance, one instance of male-to-male transmission was diagrammed. Joints \- No generalized joint laxity Limbs \- Recurrent fibular dislocation Inheritance \- Autosomal dominant ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	FIBULA, RECURRENT DISLOCATION OF HEAD OF	c1851099	25,024	omim	https://www.omim.org/entry/135800	2019-09-22T16:41:08	{"mesh": ["C565011"], "omim": ["135800"]}
A number sign (#) is used with this entry because Hermansky-Pudlak syndrome-6 (HPS6) is caused by homozygous or compound heterozygous mutation in the HPS6 gene (607522) on chromosome 10q24. For a phenotypic description and a discussion of genetic heterogeneity of Hermansky-Pudlak syndrome, see HPS1 (203300). Clinical Features Zhang et al. (2003) described a 39-year-old Belgian woman with Hermansky-Pudlak syndrome. She had oculocutaneous albinism and frequent prolonged nosebleeds, as well as prolonged bleeding after dental extractions and surgery. She had no pulmonary or gastrointestinal symptoms. Her platelet count was normal, and her bleeding time was moderately prolonged. Platelet function test showed reduced secretion in response to ATP. Electron microscopy of her platelets showed only very rare dense granules. Her parents had no known consanguinity, but both were from the same small region of east Flanders. A brother was similarly affected. Schreyer-Shafir et al. (2006) studied a large consanguineous Israeli Bedouin family in which the Hermansky-Pudlak syndrome phenotype was characterized mainly by oculocutaneous albinism. Electron microscopic studies of platelets showed absence of dense bodies, consistent with HPS, and confocal microscopy revealed abnormal distribution of LAMP3 (605883) in patient fibroblasts, indicating abnormal trafficking of lysosomal-related organelles. The findings expanded the phenotype associated with mutations in the HPS6 gene. Huizing et al. (2009) described 4 patients with Hermansky-Pudlak syndrome-6. The first was a 36-year-old woman of Irish and German descent who was found to have partial albinism and nystagmus at age 5 months, but diagnosis was not made until age 26 when bleeding complications were followed up, revealing an absence of platelet dense bodies. She also had multiple abdominal surgeries for hernia, imperforate anus, and gluteal flap repairs. She had other medical problems, including 4 miscarriages, endometriosis, frequent upper respiratory and urinary tract infections, incontinence, migraine headaches, and hearing loss. However, she did not have granulomatous colitis, and renal and pulmonary functions were normal. The second patient was a 22-year-old man of northern European descent who had nystagmus at birth and was diagnosed with oculocutaneous albinism at age 3 months. Although bruising and bleeding after trauma were noted in childhood, he was not diagnosed with HPS until age 16 years, when laboratory studies showed absence of platelet dense granules. There was no renal or lung disease. The third was a 13-year-old girl of German and Dutch descent who had rotary nystagmus in infancy and was diagnosed with oculocutaneous albinism. She had global delayed development and easy bruising. Platelet storage pool deficiency and absence of dense bodies were noted at age 4 years. The fourth patient, a 52-year-old Italian man, also had rotary nystagmus at birth and bruising in childhood. He was diagnosed at age 44 years only when he was found to have gastrointestinal symptoms and oculocutaneous albinism. Laboratory studies showed iron-deficiency anemia and low vitamin B12. There was no interstitial lung disease or renal involvement. Huizing et al. (2009) concluded that patients with HPS6 appear to have clinical features similar to those of other BLOC2-deficient patients, that is, patients with HPS3 (614072) and HPS5 (614074). Miyamichi et al. (2016) reported a 4-year-old Japanese girl and her 6-month-old sister who had oculocutaneous albinism and absence of platelet dense bodies. Both sisters had light brown hair and fair skin, and both showed congenital nystagmus and exotropia, as well as iris transillumination. Their ocular fundi were hypopigmented, with lack of macular ring reflexes, and optical coherence tomography (OCT) showed bilateral foveal hypoplasia. Although electron microscopy of their platelets showed absence of dense bodies, their platelet counts and bleeding times were normal, as were von Willebrand factor (613160) levels and prothrombin (176930) and partial thromboplastin (134390) times. There was no history of prolonged bleeding and no bleeding manifestations occurred over a 5-year follow-up period. In addition, chest x-rays showed no abnormalities, and heart was normal by ultrasound. Mapping Zhang et al. (2003) mapped the HPS6 gene to chromosome 10q24.32. Molecular Genetics In a 39-year-old Belgian woman with HPS, Zhang et al. (2003) identified a homozygous 4-bp deletion (607522.0001) in the HPS6 gene. In affected members of a large consanguineous Israeli Bedouin family with Hermansky-Pudlak syndrome, who exhibited primarily oculocutaneous albinism, Schreyer-Shafir et al. (2006) identified homozygosity for a 1-bp insertion in the HPS6 gene (607522.0002). Huizing et al. (2009) identified homozygous or compound heterozygous mutations (607522.0003-607522.0007) in the HPS6 gene in 4 unrelated patients with Hermansky-Pudlak syndrome. All mutations except 1 resulted in a truncated protein. The phenotype was characterized by early-onset nystagmus, oculocutaneous albinism, and a mild bleeding diathesis, but no pulmonary fibrosis, granulomatous colitis, or renal involvement. However, 2 patients had gastrointestinal symptoms. In vitro cellular studies performed on patient melanocytes indicated aberrant cytoplasmic distribution patterns of melanogenic proteins and increased trafficking of TYRP1 (115501) through the plasma membrane, indicating a defect in lysosomal-related organelles. In 2 Japanese sisters with oculocutaneous albinism (OCA) and absence of platelet dense bodies, who were negative for mutation in known OCA-associated genes, Miyamichi et al. (2016) performed whole-exome sequencing and identified compound heterozygosity for a 1-bp deletion (607522.0009) and a nonsense mutation (Q680X; 607522.0010) in the HPS6 gene. The authors stated that these patients broadened the phenotypic definition of HPS, and noted that this was the first report of HPS in Japanese patients. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Reduced visual acuity \- Nystagmus \- Strabismus \- Photophobia (1 patient) \- Iris transillumination \- Hypopigmentation of fundus \- Marked choroidal vessels \- Absent foveal reflex \- Absent macular reflex \- Macular hypoplasia \- Ocular albinism Nose \- Frequent nosebleeds (in some patients) Teeth \- Prolonged bleeding on dental extractions (1 patient) RESPIRATORY Nasopharynx \- Frequent upper respiratory tract infections \- No pulmonary fibrosis reported ABDOMEN Gastrointestinal \- No granulomatous colitis reported GENITOURINARY Internal Genitalia (Female) \- Heavy menstruation SKIN, NAILS, & HAIR Skin \- Light or hypopigmented skin compared to unaffected family members \- Easy bruising \- Recurrent purulent skin infections (in some patients) Nails \- Slow nail growth (1 patient) Hair \- Fair or lighter-colored scalp hair, eyebrows, and eyelashes than unaffected family members NEUROLOGIC Central Nervous System \- Global developmental delay (1 patient) HEMATOLOGY \- Prolonged bleeding time \- Bleeding tendency \- Platelets show reduced secretion in response to ATP \- Platelets lack dense bodies on electron microscopy MISCELLANEOUS \- Predominant manifestation is oculocutaneous albinism in some patients MOLECULAR BASIS \- Caused by mutation in the HPS6 gene (HPS6, 607522.0001 ) ▲ 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	HERMANSKY-PUDLAK SYNDROME 6	c0079504	25,025	omim	https://www.omim.org/entry/614075	2019-09-22T15:56:37	{"doid": ["0060544"], "mesh": ["D022861"], "omim": ["614075"], "orphanet": ["79430", "231512"], "genereviews": ["NBK1287"]}
Serious and potentially fatal infection caused by Candida yeast Invasive candidiasis SpecialtyInfectious disease Symptomsfever and chills Invasive candidiasis is an infection (candidiasis) that can be caused by various species of Candida yeast. Unlike Candida infections of the mouth and throat (oral candidiasis) or vagina (Candidal vulvovaginitis), invasive candidiasis is a serious, progressive, and potentially fatal infection that can affect the blood (fungemia), heart, brain, eyes, bones, and other parts of the body.[1][2] ## Contents * 1 Signs and symptoms * 1.1 Presentation * 2 Cause * 2.1 Resistance * 2.2 Emergent species * 3 Risk factors * 3.1 Transmission * 4 Diagnosis * 5 Prevention * 6 Treatment * 7 Epidemiology * 8 References * 9 Further reading * 10 External links ## Signs and symptoms[edit] Symptoms of invasive candidiasis can be confused with other medical conditions, however, the most common symptoms are fever and chills that do not improve with antibiotic treatment. Other symptoms develop as the infection spreads, depending on which parts of the body are involved.[3][2] ### Presentation[edit] Invasive candidiasis can manifest as serious diseases including as fungemia, endocarditis, endophthalmitis, osteomyelitis, and central nervous system infections.[4] ## Cause[edit] Invasive candidiasis is caused by 15 of the more than 150 known species of Candida. These species, all confirmed by isolation from patients, are: C. albicans, C. glabrata, C. tropicalis, C. parapsilosis, C. krusei, C. guilliermondii, C. lusitaniae, C. dubliniensis, C. pelliculosa, C. kefyr, C. lipolytica, C. famata, C. inconspicua, C. rugosa, and C. norvegensis.[4] Over the last 20–30 years, C. albicans has been responsible for 95% of infections, with, C. glabrata, C. parapsilosis, C. tropicalis, and C. krusei causing the majority of the remaining cases.[4] Recently, C. auris, a species first reported in 2009, has been found to cause invasive candidiasis. C. auris has attracted attention because it can be resistant to the antifungal medications used to treat candidiasis.[5] ### Resistance[edit] Resistance to antifungal treatment can arise from species with intrinsic resistance that experience selection pressure or spontaneous induction of resistance in isolates from normally susceptible species. For Candida, the most common is the former, as seen by the emergence of resistant C. glabrata following the introduction of fluconazole and of C. parapsilosis where there was increased use of echinocandins. Insufficient dosing of azoles has also led to the emergence of resistance. Observed rates of echinocandin resistance for C. glabrata are between 2 and 12%. Acquired echinocandin resistance has also been reported for C. albicans, C. tropicalis, C. krusei, C. kefyr, C. lusitaniae, and C. dubliniensis. ### Emergent species[edit] Candida auris is an emerging multidrug-resistant yeast that can cause invasive candidiasis and is associated with high mortality.[6] It was first described in 2009.[6] Since then, C. auris infections, specifically fungemia, have been reported from South Korea, India, South Africa, Kuwait, Colombia, Venezuela, Pakistan, the United Kingdom and the United States.[6] The strains isolated in each region are genetically distinct, indicating that this species is emerging in different locations.[6] The reason for this pattern is unknown.[6] ## Risk factors[edit] Patients with the following conditions, treatments or situations are at increased risk for invasive candidiasis.[4][2][7] * Critical illness * Long-term intensive care unit stay * Abdominal surgery (aggravated by anastomotic leakage or repeat laparotomies) * Immunosuppressive diseases * Acute necrotizing pancreatitis * Malignant hematologic disease * Solid-organ transplantation * Hematopoietic stem cell transplantation * Solid-organ tumors * Neonates (especially low birth weight and preterm infants) * Broad-spectrum antibiotic treatment * Central venous catheter * Internal prosthetic device * Total parenteral nutrition * Hemodialysis * Glucocorticoid use * Chemotherapy * Noninvasive Candida colonization (particularly if multifocal) ### Transmission[edit] Invasive candidiasis is a nosocomial infection with the majority of cases associated with hospital stays.[4] ## Diagnosis[edit] Because many Candida species are part of the human microbiota, their presence in the mouth, the vagina, sputum, urine, stool, or skin is not definitive evidence for invasive candidiasis.[2] Positive culture of Candida species from normally sterile sites, such as blood, cerebrospinal fluid, pericardium, pericardial fluid, or biopsied tissue, is definitive evidence of invasive candidiasis.[2] Diagnosis by culturing allows subsequent susceptibility testing of causative species.[8][7] Sensitivity of blood culture is far from ideal, with a sensitivity reported to be between 21 and 71%.[7] Additionally, whereas blood culture can establish a diagnosis during fungemia, the blood may test negative for deep-seated infections because candida may have been successfully cleared from the blood.[7] Diagnosis of invasive candidiasis is supported by histopathologic evidence (for example, yeast cells or hyphae) observed in specimens of affected tissues.[2] Additionally, elevated serum β-glucan can demonstrate invasive candidiasis while a negative test suggests a low likelihood of systemic infection.[9][2] The emergence of multidrug-resistant C. auris as a cause of invasive candidiasis has necessitated additional testing in some settings.[6] C. auris-caused invasive candidiasis is associated with high mortality.[6] Many C. auris isolates have been found to be resistant to one or more of the three major antifungal classes (azoles, echinocandins, and polyenes) with some resistant to all three classes – severely limiting treatment options.[6] Biochemical-based tests currently used in many laboratories to identify fungi, including API 20C AUX and VITEK-2, cannot differentiate C. auris from related species (for example, C. auris can be identified as C. haemulonii).[6] Therefore, the Centers for Disease Control and Prevention recommends using a diagnostic method based on matrix-assisted laser desorption/ionization-time of flight mass spectrometry or a molecular method based on sequencing the D1-D2 region of the 28s rDNA to identify C. auris in settings where it may be present.[6] ## Prevention[edit] Preventive antifungal treatment is supported by studies, but only for specific high-risk groups in intensive care units with conditions that put them at high risk for the disease.[7] For example, one group would be patients recovering from abdominal surgery that may have gastrointestinal perforations or anastomotic leakage.[7] Antifungal prophylaxis can reduce the incidence of fungemia by approximately 50%, but has not been shown to improve survival.[7] A major challenge limiting the number of patients receiving prophylaxis to only those that can potentially benefit, thereby avoiding the creation of selective pressure that can lead to the emergence of resistance.[7] ## Treatment[edit] Antifungals are used for treatment with the specific type and dose depending on the patient's age, immune status, and specifics of the infection. For most adults, the initial treatment is an echinocandin class antifungal (caspofungin, micafungin, or anidulafungin) given intravenously. Fluconazole, amphotericin B, and other antifungals may also be used.[10] Treatment normally continues for two weeks after resolution of signs and symptoms and Candida yeasts can no longer can be cultured from blood samples. Some forms of invasive candidiasis, such as infections in the bones, joints, heart, or central nervous system, usually need to be treated for a longer period.[10] Retrospective observational studies suggest that prompt presumptive antifungal therapy (based on symptoms or biomarkers) is effective and can reduce mortality.[7] ## Epidemiology[edit] Invasive candidiasis is estimated to affect more than 250,000 people and cause more than 50,000 deaths worldwide every year.[7] The CDC estimates that approximately 46,000 cases of healthcare-associated invasive candidiasis occur each year in the US.[11] The estimated mortality attributable to fungemia is 19-40%.[7][11] However, because the majority of people who develop invasive candidiasis are already sick, it can be difficult to determine if the cause of death is directly attributable to the fungal infection.[11] Fungemia is one of the most common bloodstream infections in the United States.[11] In general, observed incidence rates have been stable or trending higher but declining rates have been achieved with improvements in hygiene and disease management.[7] Deep-seated infections in bones, muscles, joints, eyes, or central nervous system can arise from a bloodstream infection or direct inoculation of Candida may occur, for example, during intestinal surgery.[7] The distribution of Candida species causing invasive candidiasis has changed over the past decades.[7] C. albicans had been the dominant pathogen but now accounts for just half of the isolates.[7] Increasing dominance of C. glabrata in northern Europe, the United States, and Canada has been observed while C. parapsilosis has become more prominent in southern Europe, Asia, and South America.[7] Regional species distribution guides treatment recommendations since the species exhibit different susceptibilities to azole and echinocandin classes of antifungals.[7] The virulence of Candida species differs considerably, with C. parapsilosis and C. krusei being less virulent than C. albicans, C. tropicalis, and C. glabrata.[7] This variation is reflected in mortality rates.[7] ## References[edit] 1. ^ "Invasive Candidiasis \| Candidiasis \| Types of Fungal Diseases \| Fungal Diseases \| CDC". www.cdc.gov. Retrieved 2017-04-02. 2. ^ a b c d e f g "Candidiasis (Invasive) – Infectious Diseases". MSD Manual Professional Edition. Retrieved 2017-04-06. 3. ^ "Symptoms \| Invasive Candidiasis \| Candidiasis \| Types of Diseases \| Fungal Diseases \| CDC". www.cdc.gov. Retrieved 2017-04-03. 4. ^ a b c d e Yapar, Nur (2014-01-01). "Epidemiology and risk factors for invasive candidiasis". Therapeutics and Clinical Risk Management. 10: 95–105. doi:10.2147/TCRM.S40160. ISSN 1176-6336. PMC 3928396. PMID 24611015. 5. ^ "Fatal Fungus Linked to 4 New Deaths – What You Need to Know". 2016-11-07. Retrieved 2017-04-04. 6. ^ a b c d e f g h i j "Clinical Alert to U.S. Healthcare Facilities – Fungal Diseases \| CDC". www.cdc.gov. June 2016. Retrieved 2017-04-06. 7. ^ a b c d e f g h i j k l m n o p q r s Kullberg, Bart Jan; Arendrup, Maiken C. (2015-10-08). "Invasive Candidiasis". The New England Journal of Medicine. 373 (15): 1445–1456. doi:10.1056/NEJMra1315399. hdl:2066/152392. ISSN 1533-4406. PMID 26444731. 8. ^ "Diagnosis and Testing \| Invasive Candidiasis \| Candidiasis \| Types of Diseases \| Fungal Diseases \| CDC". www.cdc.gov. Retrieved 2017-04-03. 9. ^ Vincenzi, V.; Fioroni, E.; Benvegnù, B.; De Angelis, M.; Bartolucci, L.; Gradoli, C.; Valori, C. (1985-05-12). "[Effects of calcium antagonists on pancreatic endocrine secretion]". Minerva Medica. 76 (19–20): 919–921. ISSN 0026-4806. PMID 3889722. 10. ^ a b "Treatment \| Invasive Candidiasis \| Candidiasis \| Types of Diseases \| Fungal Diseases \| CDC". www.cdc.gov. Retrieved 2017-04-03. 11. ^ a b c d "Statistics \| Invasive Candidiasis \| Candidiasis \| Types of Diseases \| Fungal Diseases \| CDC". www.cdc.gov. Retrieved 2017-04-03. ## Further reading[edit] * Pfaller MA, Diekema DJ (2007). "Epidemiology of invasive candidiasis: a persistent public health problem". Clinical Microbiology Reviews. 20 (1): 133–163. doi:10.1128/CMR.00029-06. PMC 1797637. PMID 17223626. (Review). * Yapar N (2014). "Epidemiology and risk factors for invasive candidiasis". Therapeutics and Clinical Risk Management. 10: 95–105. doi:10.2147/TCRM.S40160. PMC 3928396. PMID 24611015. (Review). ## External links[edit] Classification D * ICD-10: B37 * MeSH: D058365 * Candidiasis (Invasive) in the MSD (Merck) Manual * Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Invasive candidiasis	c1609535	25,026	wikipedia	https://en.wikipedia.org/wiki/Invasive_candidiasis	2021-01-18T18:32:28	{"mesh": ["D058365"], "umls": ["C1609535"], "wikidata": ["Q29887808"]}
Autosomal recessive centronuclear myopathy (AR-CNM) is a type of centronuclear myopathy, which is a group of rare, inherited conditions that affect the muscles. In AR-CNM, specifically, affected people generally begin showing signs and symptoms during infancy or early childhood. The features of the condition can vary but may include progressive muscle weakness, foot abnormalities, high-arched palate, scoliosis, ptosis, mild to severe breathing problems, delayed motor milestones and cardiomyopathy (less commonly). Most cases of AR-CNM are caused by changes (mutations) in the BIN1 gene; however, some affected families are reported to have mutations in the SPEG, TTN, or RYR1 genes. The condition is inherited in an autosomal recessive manner. Treatment is based on the signs and symptoms present in each person and may include physical and/or occupational therapy and assistive devices to help with mobility, eating and/or breathing. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Autosomal recessive centronuclear myopathy	c3645536	25,027	gard	https://rarediseases.info.nih.gov/diseases/12718/autosomal-recessive-centronuclear-myopathy	2021-01-18T18:01:55	{"mesh": ["D020914"], "omim": ["255200 "], "orphanet": ["169186"], "synonyms": ["Myopathy, centronuclear, autosomal recessive", "Myopathy, Centronuclear, 2", "AR-CNM"]}
Von Voss-Cherstvoy syndrome is a very rare disorder with phocomelia of upper limbs, encephalocele, variable brain anomalies, urogenital abnormalities, and thrombocytopenia. ## Epidemiology Less than 15 cases have been reported. ## Clinical description The spectrum of upper limb defects varies from radial agenesis and phocomelia to amelia. A meningoencephalocele is constant. The intellectual development may be normal. ## Etiology Pathogenesis and cause of this syndrome are unknown. ## Genetic counseling Parental consanguinity reported in a family suggests an autosomal recessive 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	Von Voss-Cherstvoy syndrome	c1857226	25,028	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3439	2021-01-23T18:03:14	{"gard": ["1894"], "mesh": ["C565618"], "omim": ["223340"], "umls": ["C1857226"], "icd-10": ["Q87.8"], "synonyms": ["DK phocomelia syndrome", "Phocomelia-thrombocytopenia-encephalocele-urogenital malformations syndrome"]}
Surfactant metabolism dysfunction Other namesPrimary interstitial lung disease specific to childhood due to pulmonary surfactant protein anomalies SpecialtyPulmonology Surfactant metabolism dysfunction is a condition where pulmonary surfactant is insufficient for adequate respiration. Surface tension at the liquid-air interphase in the alveoli makes the air sacs prone to collapsing post expiration. This is due to the fact that water molecules in the liquid-air surface of alveoli are more attracted to one another than they are to molecules in the air. For sphere-like structures like alveoli, water molecules line the inner walls of the air sacs and stick tightly together through hydrogen bonds. These intermolecular forces put great restraint on the inner walls of the air sac, tighten the surface all together, and unyielding to stretch for inhalation. Thus, without something to alleviate this surface tension, alveoli can collapse and cannot be filled up again. Surfactant is essential mixture that is released into the air-facing surface of inner walls of air sacs to lessen the strength of surface tension. This mixture inserts itself among water molecules and breaks up hydrogen bonds that hold the tension.[1] Multiple lung diseases, like ISD or RDS, in newborns and late-onsets cases have been linked to dysfunction of surfactant metabolism. Surfactant is a mixture of 90% phospholipids and 10% other proteins, produced by epithelial type II cells in the alveolar. This mixture is made and packaged into lysosomally- derived structures called lamellar bodies. Lamellar bodies are then secreted into the liquid-air interphase surface of alveolar through membrane fusion initiated by influx of Ca2+.[2] Released pulmonary surfactant acts as a protective layer to prevent alveolar from collapsing due to surface tension. Furthermore, surfactants also contains some innate immune components to defend against pulmonary infections. Surfactant is classified into two types of proteins, hydrophilic proteins that are responsible for innate immune system, and hydrophobic proteins that carry out physical functions of pulmonary surfactant.[3] Surfactant metabolism dysfunction involves mutations or malfunctions of those hydrophobic proteins that lead to ineffective surfactant layer to protect alveolus integrity.[3] SP-B and SP-C are the two hydrophobic surfactant proteins that participate in its physical functions; these proteins are encoded by SFTPB and SFTPC genes on chromosomes 2 and 8 respectively.[4] Thus, mutations on these genes produce incomplete or nonfunctioning SP-B and SP-C proteins and lead to lung diseases. Both SP-B and SP-C are synthesized in epithelial type II cells as large precursor proteins (proSP-B and proSP-C) and subsequently cleaved by proteolytic enzymes at both amino and carboxyl termini to produce functional mature proteins.[3] proSP-B and proSP-C are first made in the endoplasmic reticulum of epithelial type II cell, they are then translocated through Golgi apparatus to multivesicular bodies for delivery to lamellar bodies. During this transition, proteolytic processing begins to cleave precursor proteins. Once multivescular body reaches the membrane of lamellar body, both membranes fuse together so that processed proteins can be transported into lamellar body, where last steps of maturation for both SP-B and SP-C occur.[4] When lamellar body is ready to be secreted, exocytosis is initiated through influx of Ca2+, and lamellar membrane fuses with plasma membrane to release surfactant phospholipid contents into the surface of the cell.[2] SP-B and SP-C are responsible to carry out adsorption of the lipid monolayer at the liquid-air interphase to prevent post expiration atelectasis. Used surfactant phospholipid materials are taken up into epithelial type II cells by pulmonary macrophages.[2] Another important protein that contributes to outcome of surfactant metabolism dysfunction is ABCA3, a transmembrane phospholipid transporter in lamellar body. ABCA3 has two ATP binding sites in the cytoplasmic domain to power phospholipid transportation through ATP hydrolysis. ABCA3 is synthesized in endoplasmic reticulum and transported through Golgi apparatus to the membrane of lamellar body.[4] Once inserted into the membrane, ABCA3 can help deliver surfactant lipids into the lumen of lamellar body, and create tightly packed internal environment of surfactant lipids and surfactant proteins. Mutations in ABCA3 cause failure in lamellar body synthesis and result in decreased production of surfactant, along with deficiency of SP-B and SP-C.[3] ## Contents * 1 Cause * 1.1 SFTPB mutations * 1.2 SFTPC mutations * 1.3 ABCA3 mutations * 2 Diagnosis * 2.1 Types * 3 Treatment * 4 See also * 5 References * 6 Further reading * 7 External links ## Cause[edit] Surfactant metabolism dysfunction describes a group of dysfunctions caused by different mutations in surfactant related genes.Severe deficiency of pulmonary surfactant due to disturbed metabolism of any of these proteins can lead to some form of interstitial lung disease in newborns and adults. These conditions share similar pathophysiology and overlapping phenotypes because surfactant gene products interactively communicate and control one another.[3] Thus, dysfunction of a surfactant protein, or relating protein, generates deficiencies of others.[citation needed] ### SFTPB mutations[edit] Most disease-causing mutations in SFTPB result in a complete lack of mature SP-B protein 265120. Lung disease is inherited in an autosomal recessive manner, requiring mutations in both alleles. Surfactant produced by infants with SP-B deficiency is abnormal in composition and does not function normally in lowering surface tension.[citation needed] More than 40 different mutations along the length of SFTPB gene have been accounted for in surfactant metabolism dysfunction. SFTPB mutations are inherited in autosomal recessive fashion, loss-of-function mutation on both alleles are required for full expression of disease. About 2/3 or 60%-70% of those accounted disease-causing alleles come from a frameshift mutation, called 121ins2, on exon 4 of SFTPB gene, which also accounts for ~65% of US cases. The rest of the mutated alleles come from nonsense, missense, splice-site mutations, and other possible insertion and deletion mutations throughout the entire gene.[4] These mutations cause total absence or loss-of-function of SP-B and lead to imbalance in surfactant homeostasis. Since SP-B has a major role in surfactant biogenesis and spreading of surfactant and lipid layer, any disruption to existence of SP-B results in ineffective respiration and lethal pulmonary conditions at birth.[5] Pathology manifestation in full-term infant resembles characteristics of newborn with Respiratory Distress Syndrome.[6] Imaging of epithelial type II cells with SP-B deficiency shows immature lamellar bodies without tightly packed membranes, but rather with loose and unorganized membranes. The ratio of phospholipid-protein also decreases with abnormal phospholipids. In addition, surfactant collected from SP-B deficiency epithelial type II cells is not as effective in lowering surface tension and creating film as normal surfactant.[3] Immunohistochemical features of SP-B deficiency show decreased levels of proSP-B and SP-B proteins, along with increased presence of immuno protein SP-A and partially processed intermediate peptides of proSP-C.[4] Appearance of partially processed proSP-C shows significance of mature SP-B in biogenesis and processing of SP-C. Absences of both proSP-B and SP-B proteins are observed in frameshift and nonsense mutations of SFTPB, while low level of proSP-B is detected in missense, in-frame deletionof insertion mutations. However, these mutations prevent proSP-B from fully mature into SP-B, resulting in deficiency of SP-B and surfactant. ### SFTPC mutations[edit] Familial cases of SP-C dysfunction 610913 are inherited in an autosomal dominant pattern, although the onset and severity of lung disease are highly variable, even within the same family.[citation needed] More than 40 distinct mutation variations in SFTPC gene have also been described in patients. Wild-type SP-C proteins are embedded inside the phospholipid bilayer of epithelial type II cell and function to generate and maintain monolayer of surfactant on alveolar surface.[4] Individuals with mutated SFTPC genes tend to manifest lung diseases in late childhood or adulthood. Mutated alleles are inherited in autosomal dominant fashion, although de novo mutations can also cause sporadic emergence of diseases. The age of onset and severity vary significantly among patients with SFTPC mutations, some only manifest symptoms in fifth or sixth decade.[3] Most of these mutations are missense, but there have been recordings of frameshift, splice-site mutations, together with small insertions or deletions along the carboxyl terminal of SFTPC. Mutations in SFTPC gene are thought to prevent proSP-C peptides from being fully processed into mature SP-C proteins. ProSP-C proteins tend to self-accumulate along the secretory pathway, due to high hydrophobic nature, and may activate cellular destruction response. SFTPC mutations cause proSP-C proteins to aggregate and misfold during secretory process.[3] These folded proteins trigger unfolded protein response (UPR) and cellular apoptosis to get rid of clusters of mutated peptides. Patients with SP-C dysfunction show lack of mature SP-C in epithelial type II cells and up-regulation of UPR.[4] SFTPC mutation with highest occurrence frequency is substitution of threonine for isoleucine in codon 73, termed I73T, found in more than 25% of patients with SP-C related disorders. Staining of proSP-C shows diffuse staining strictly in cytoplasm and accumulation of immunoreactive substances surrounding the nucleus.[4] Evaluation of diseases related to SFTPC mutations show association with chronic parenchymal lung disease.[citation needed] ### ABCA3 mutations[edit] Mutations in ABCA3 appear to be the most common cause of genetic surfactant dysfunction in humans.[7][8][9] The mutations result in a loss of or reduced function of the ABCA3 protein, and are inherited in an autosomal recessive manner 610921. There are more than 150 different mutations throughout ABCA3 gene with various allelic heterogeneity, making it the biggest class of genetic cause of surfactant dysfunction.Like SP-B deficiency, ABCA3 mutations are inherited in autosomal recessive trait. Mutations of ABCA3 consist of missense, nonsense, frameshift, splice-cite, insertion or deletion.[4] These mutations are classified into two types of ABCA3 mutations, those that preclude normal trafficking of ABCA3 from ER to lamellar membrane, and those that affect ATP-binding ability of ABCA3 needed for phospholipid transportation.[3] Due to its roles in lamellar body biogenesis and maturation of surfactant proteins, epithelial type II cells with altered ABCA3 exhibit premature lamellar bodies and damaged maturation of SP-B/SP-C. Surfactant samples from patients with ABCA3 deficiency do not lower surface tension as effectively. Affected surface tension ability results from incomplete formation of lamellar bodies, due to lack of lipid influx by ABCA3. Immunostaining of SP-B in ABCA3 patients show decreased level of mature SP-B and impaired process of proSP-B to SP-B, thus, confirming why ABCA3 dysfunction leads to severe surfactant metabolism dysfunction.[4] ## Diagnosis[edit] ### Types[edit] Type OMIM Gene Locus SMDP1 265120 SFTPB 2p12 SMDP2 610913 SPTPC 8p21 SMDP3 610921 ABCA3 16p13 SMDP4 300770 CSF2RA Xp Non-invasive genetic testing can be used to infer possible interstitial lung disorders caused by surfactant metabolism dysfunction. Although these sequencing tests can take up to several weeks, which may not be so useful in case of acute respiratory problems in newborns. Overlapping phenotypes of surfactant metabolism dysfunction and other interstitial lung diseases make it hard to propose definitive diagnosis for surfactant disorders. Overall testings, family history, external factors, and clinical presentations should all be considered to diagnose surfactant metabolism dysfunction. Testing for surfactant metabolism dysfunction should be considered for newborns with diffuse lung disease or hypoxemia, especially in families with history of neonatal lung diseases or ILD in adults. Neonatal and adult onset lung diseases with unfound causes should also be tested early for surfactant dysfunction.[3] ABCA3 and SP-B dysfunctions manifest in newborns and progress aggressively within the first few months of life, thus, testing for ABCA3 and SP-B disorders should preclude those for SP-C, especially when infants are showing symptoms of ILD or diffuse lung disease. Distinctions between SP-B and ABCA3 are ABCA3 tends to occur in families with neonatal lung disease history, and SP-B testing almost unneeded in older children.[3] Late on-set conditions with inheritance in dominant fashion should infer SP-C dysfunction. Antibodies against proSP-B, proSP-C, SP-B, SP-C, and ABCA3 have been thoroughly developed, which makes detection for these proteins highly accessible and accurate.[4] Immuno staining of each of these type of surfactant dysfunction differs in absence and presence of specific proteins and propeptides, thus immunohistochemisty can help decipher which type of deficiency is being dealt with. In addition, hypothyroidism can cause damaged production of NKX2.1 proteins, which can lead to insufficient transcription of multiple surfactant proteins.[citation needed] ## Treatment[edit] Neonates with surfactant metabolism dysfunctions, especially those with SP-B disorder, only have lung transplantation as one possible choice of treatment.[3] Children with lung transplant due to surfactant metabolism dysfunction perform on similar level to those with transplant for due to other reasons.[3] Some less severe cases of ABCA3 dysfunctions manifest in late childhood or adult hood are due to missense mutations that result in semi-sufficient levels of active surfactant, while SP-C clinical presentation varies greatly depending on level of penetration of the mutated alleles.[4] ## See also[edit] * Congenital hypothyroidism * Infant respiratory distress syndrome * Interstitial lung disease * Persistent pulmonary hypertension of the newborn * Pulmonary alveolar proteinosis * Respiratory care ## References[edit] 1. ^ Seadler, Benjamin D.; Kaushik, Ravi; Sharma, Sandeep (2020), "Physiology, Alveolar Tension", StatPearls, StatPearls Publishing, PMID 30969647, retrieved 2020-04-24 2. ^ a b c Olmeda, Bárbara; Martínez-Calle, Marta; Pérez-Gil, Jesus (2017-01-01). "Pulmonary surfactant metabolism in the alveolar airspace: Biogenesis, extracellular conversions, recycling". Annals of Anatomy - Anatomischer Anzeiger. 209: 78–92. doi:10.1016/j.aanat.2016.09.008. ISSN 0940-9602. PMID 27773772. 3. ^ a b c d e f g h i j k l m Gower, W. Adam; Nogee, Lawrence M. (December 2011). "Surfactant Dysfunction". Paediatric Respiratory Reviews. 12 (4): 223–229. doi:10.1016/j.prrv.2011.01.005. ISSN 1526-0542. PMC 3201772. PMID 22018035. 4. ^ a b c d e f g h i j k l Wert, Susan E.; Whitsett, Jeffrey A.; Nogee, Lawrence M. (2009). "Genetic Disorders of Surfactant Dysfunction". Pediatric and Developmental Pathology. 12 (4): 253–274. doi:10.2350/09-01-0586.1. ISSN 1093-5266. PMC 2987676. PMID 19220077. 5. ^ Hawgood, Samuel; Derrick, Matthew; Poulain, Francis (1998-11-19). "Structure and properties of surfactant protein B". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1408 (2): 150–160. doi:10.1016/S0925-4439(98)00064-7. ISSN 0925-4439. PMID 9813296. 6. ^ McFetridge, Lynne; McMorrow, Aoife; Morrison, Patrick J; Shields, Michael D (January 2009). "Surfactant Metabolism Dysfunction and Childhood Interstitial Lung Disease (chILD)". The Ulster Medical Journal. 78 (1): 7–9. ISSN 0041-6193. PMC 2629012. PMID 19252722. 7. ^ Brasch, F; Griese, M; Tredano, M; Johnen, G; Ochs, M; Rieger, C; Mulugeta, S; Müller, KM; Bahuau, M; Beers, MF (Jul 2004). "Interstitial lung disease in a baby with a de novo mutation in the SFTPC gene". The European Respiratory Journal. 24 (1): 30–9. doi:10.1183/09031936.04.00000104. PMID 15293602. 8. ^ Shulenin, S; Nogee, LM; Annilo, T; Wert, SE; Whitsett, JA; Dean, M (Mar 25, 2004). "ABCA3 gene mutations in newborns with fatal surfactant deficiency". The New England Journal of Medicine. 350 (13): 1296–303. doi:10.1056/NEJMoa032178. PMID 15044640. 9. ^ Somaschini, M; Nogee, LM; Sassi, I; Danhaive, O; Presi, S; Boldrini, R; Montrasio, C; Ferrari, M; Wert, SE; Carrera, P (Jun 2007). "Unexplained neonatal respiratory distress due to congenital surfactant deficiency". The Journal of Pediatrics. 150 (6): 649–53, 653.e1. doi:10.1016/j.jpeds.2007.03.008. PMID 17517255. ## Further reading[edit] * Reference, Genetics Home. "surfactant dysfunction". Genetics Home Reference. Retrieved 5 November 2017. ## External links[edit] Classification D External resources * Orphanet: 100049 * v * t * e Genetic disorder, membrane: ABC-transporter disorders ABCA * ABCA1 (Tangier disease) * ABCA3 (Surfactant metabolism dysfunction 3) * ABCA4 (Stargardt disease 1, Retinitis pigmentosa 19) * ABCA12 (Harlequin-type ichthyosis, Lamellar ichthyosis 2) ABCB * ABCB4 (Progressive familial intrahepatic cholestasis 3) * ABCB7 (ASAT) * ABCB11 (Progressive familial intrahepatic cholestasis 2) ABCC * ABCC2 (Dubin–Johnson syndrome) * ABCC6 (Pseudoxanthoma elasticum) * ABCC7 (Cystic fibrosis) * ABCC8 (HHF1, TNDM2) * ABCC9 (Dilated cardiomyopathy 1O) ABCD * ABCD1 (Adrenoleukodystrophy, Adrenomyeloneuropathy) ABCG * ABCG5 (Sitosterolemia) * ABCG8 (Gallbladder disease 4, Sitosterolemia) see also ABC transporters * v * t * e Cell surface receptor deficiencies G protein-coupled receptor (including hormone) Class A * TSHR (Congenital hypothyroidism 1) * LHCGR (Luteinizing hormone insensitivity, Leydig cell hypoplasia, Male-limited precocious puberty) * FSHR (Follicle-stimulating hormone insensitivity, XX gonadal dysgenesis) * GnRHR (Gonadotropin-releasing hormone insensitivity) * EDNRB (ABCD syndrome, Waardenburg syndrome 4a, Hirschsprung's disease 2) * AVPR2 (Nephrogenic diabetes insipidus 1) * PTGER2 (Aspirin-induced asthma) Class B * PTH1R (Jansen's metaphyseal chondrodysplasia) Class C * CASR (Familial hypocalciuric hypercalcemia) Class F * FZD4 (Familial exudative vitreoretinopathy 1) Enzyme-linked receptor (including growth factor) RTK * ROR2 (Robinow syndrome) * FGFR1 (Pfeiffer syndrome, KAL2 Kallmann syndrome) * FGFR2 (Apert syndrome, Antley–Bixler syndrome, Pfeiffer syndrome, Crouzon syndrome, Jackson–Weiss syndrome) * FGFR3 (Achondroplasia, Hypochondroplasia, Thanatophoric dysplasia, Muenke syndrome) * INSR (Donohue syndrome * Rabson–Mendenhall syndrome) * NTRK1 (Congenital insensitivity to pain with anhidrosis) * KIT (KIT Piebaldism, Gastrointestinal stromal tumor) STPK * AMHR2 (Persistent Müllerian duct syndrome II) * TGF beta receptors: Endoglin/Alk-1/SMAD4 (Hereditary hemorrhagic telangiectasia) * TGFBR1/TGFBR2 (Loeys–Dietz syndrome) GC * GUCY2D (Leber's congenital amaurosis 1) JAK-STAT * Type I cytokine receptor: GH (Laron syndrome) * CSF2RA (Surfactant metabolism dysfunction 4) * MPL (Congenital amegakaryocytic thrombocytopenia) TNF receptor * TNFRSF1A (TNF receptor associated periodic syndrome) * TNFRSF13B (Selective immunoglobulin A deficiency 2) * TNFRSF5 (Hyper-IgM syndrome type 3) * TNFRSF13C (CVID4) * TNFRSF13B (CVID2) * TNFRSF6 (Autoimmune lymphoproliferative syndrome 1A) Lipid receptor * LRP: LRP2 (Donnai–Barrow syndrome) * LRP4 (Cenani–Lenz syndactylism) * LRP5 (Worth syndrome, Familial exudative vitreoretinopathy 4, Osteopetrosis 1) * LDLR (LDLR Familial hypercholesterolemia) Other/ungrouped * Immunoglobulin superfamily: AGM3, 6 * Integrin: LAD1 * Glanzmann's thrombasthenia * Junctional epidermolysis bullosa with pyloric atresia EDAR (EDAR hypohidrotic ectodermal dysplasia) * PTCH1 (Nevoid basal-cell carcinoma syndrome) * BMPR1A (BMPR1A juvenile polyposis syndrome) * IL2RG (X-linked severe combined immunodeficiency) See also cell surface receptors * v * t * e Cell membrane protein disorders (other than Cell surface receptor, enzymes, and cytoskeleton) Arrestin * Oguchi disease 1 Myelin * Pelizaeus–Merzbacher disease * Dejerine–Sottas disease * Charcot–Marie–Tooth disease 1B, 2J Pulmonary surfactant * Surfactant metabolism dysfunction 1, 2 Cell adhesion molecule IgSF CAM: * OFC7 Cadherin: * DSG1 * Striate palmoplantar keratoderma 1 * DSG2 * Arrhythmogenic right ventricular dysplasia 10 * DSG4 * LAH1 * DSC2 * Arrhythmogenic right ventricular dysplasia 11 Integrin: * cell surface receptor deficiencies Tetraspanin * TSPAN7 * X-Linked mental retardation 58 * TSPAN12 * Familial exudative vitreoretinopathy 5 Other * KIND1 * Kindler syndrome * HFE * HFE hereditary haemochromatosis * DYSF * Distal muscular dystrophy * Limb-girdle muscular dystrophy 2B See also other cell membrane 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	Surfactant metabolism dysfunction	None	25,029	wikipedia	https://en.wikipedia.org/wiki/Surfactant_metabolism_dysfunction	2021-01-18T18:45:57	{"wikidata": ["Q7646050"]}
## Summary ### Clinical characteristics. Prader-Willi syndrome (PWS) is characterized by severe hypotonia and feeding difficulties in early infancy, followed in later infancy or early childhood by excessive eating and gradual development of morbid obesity (unless eating is externally controlled). Motor milestones and language development are delayed. All individuals have some degree of cognitive impairment. A distinctive behavioral phenotype (with temper tantrums, stubbornness, manipulative behavior, and obsessive-compulsive characteristics) is common. Hypogonadism is present in both males and females and manifests as genital hypoplasia, incomplete pubertal development, and, in most, infertility. Short stature is common (if not treated with growth hormone); characteristic facial features, strabismus, and scoliosis are often present. ### Diagnosis/testing. Consensus clinical diagnostic criteria are accurate, but the mainstay of diagnosis is DNA methylation testing to detect abnormal parent-specific imprinting within the Prader-Willi critical region (PWCR) on chromosome 15; this testing determines whether the region is maternally inherited only (i.e., the paternally contributed region is absent) and detects more than 99% of affected individuals. DNA methylation-specific testing is important to confirm the diagnosis of PWS in all individuals, but especially in those who have atypical findings or are too young to manifest sufficient features to make the diagnosis on clinical grounds. ### Management. Treatment of manifestations: In infancy, special nipples or enteral tube feeding to assure adequate nutrition; physical therapy may improve muscle strength; hormonal and surgical treatments can be considered for cryptorchidism. In childhood, strict supervision of daily food intake based on height, weight, and body mass index (BMI) to provide energy requirements while limiting excessive weight gain (keeping BMI Z score <2 or better) and encouraging physical activity. Growth hormone replacement therapy to normalize height, increase lean body mass and mobility, and decrease fat mass. Evaluation and treatment of sleep disturbance per the general population. Educational planning should be instigated and speech therapy provided if needed. Firm limit-setting to manage behavioral problems; serotonin reuptake inhibitors are helpful for most teenagers and adults. Replacement of sex hormones at puberty produces adequate secondary sexual characteristics. N-acetylcysteine or topiramate may help reduce skin picking. Modafinil has been successful in treating daytime sleepiness in many children. In adulthood, a group home for individuals with PWS that regulates behavior and weight management may prevent morbid obesity, and growth hormone may help to maintain muscle bulk. Prevention of secondary complications: Weight control to avoid development of type 2 diabetes mellitus; calcium and vitamin D supplementation to avoid osteoporosis; if osteoporosis develops, consider treatment with a bisphosphonate. Surveillance: Infants should be screened for strabismus; routine monitoring of height, weight, and BMI to assure appropriateness of exercise program and diet; annual testing for hypothyroidism. Other: No medications are currently known to aid in controlling hyperphagia, although several are under investigation. ### Genetic counseling. PWS is caused by an absence of expression of imprinted genes in the paternally derived PWS/Angelman syndrome (AS) region (i.e., 15q11.2-q13) of chromosome 15 by one of several genetic mechanisms (paternal deletion, maternal uniparental disomy 15 and rarely an imprinting defect). The risk to the sibs of an affected child of having PWS depends on the genetic mechanism that resulted in the absence of expression of the paternally contributed 15q11.2-q13 region. The risk to sibs is typically less than 1% if the affected child has a deletion or uniparental disomy, up to 50% if the affected child has an imprinting defect, and up to 25% if a parental chromosome translocation is present. Prenatal testing is possible for pregnancies at increased risk if the underlying genetic mechanism is known. ## Diagnosis Consensus diagnostic criteria for Prader-Willi syndrome (PWS) developed in 1993 [Holm et al 1993] have proven to be accurate [Gunay-Aygun et al 2001] and continue to be useful for the clinician. However, confirmation of the diagnosis requires molecular genetic testing, which was not widely available when the criteria were developed. ### Suggestive Findings Prader-Willi syndrome should be suspected in individuals with the specific clinical findings listed below or findings on cytogenetic/FISH/chromosomal microarray. Clinical findings that should prompt diagnostic testing have been proposed based on analysis of diagnostic criteria met in individuals in whom the diagnosis of PWS has been molecularly confirmed [Gunay-Aygun et al 2001]. These differ by age group. The presence of all of the following findings at the age indicated is sufficient to justify DNA methylation analysis for PWS (see Establishing the Diagnosis): Birth to age two years * Hypotonia with poor suck (neonatal period) Age two to six years * Hypotonia with history of poor suck * Global developmental delay Age six to 12 years * History of hypotonia with poor suck (hypotonia often persists) * Global developmental delay * Excessive eating with central obesity if uncontrolled Age 13 years to adulthood * Cognitive impairment, usually mild intellectual disability * Excessive eating with central obesity if uncontrolled * Hypothalamic hypogonadism and/or typical behavior problems Cytogenetic/FISH/chromosomal microarray findings. Approximately 70% of individuals with PWS have a deletion on one chromosome 15 involving bands 15q11.2-q13, which can be detected using high-resolution chromosome studies and fluorescence in situ hybridization (FISH) testing or chromosomal microarray. Note: The typical deletion is one of two sizes: extending from the distal breakpoint (BP3) to one of two proximal breakpoints (BP1 or BP2). Clinical FISH testing detects both of these deletions and typically will not distinguish between them. Additional atypical and unique deletions occur in approximately 8% of deletion cases [Kim et al 2012]. Approximately 1% of affected individuals have a detectable chromosome rearrangement (i.e., translocation or inversion) resulting in a deletion of bands 15q11.2-q13. Fewer than 1% of individuals have a "balanced" chromosome rearrangement breaking within 15q11.2-q13 and detectable by chromosome analysis and FISH. ### Establishing the Diagnosis The diagnosis of PWS is established in a proband with DNA methylation analysis demonstrating abnormal parent-specific imprinting within the Prader-Willi critical region (PWCR) on chromosome 15 in which the region demonstrates maternal-only imprinting (i.e., the absence of paternal-only expressed genes). Three main molecular mechanisms that result in PWS include paternal deletion, maternal uniparental disomy (UPD) 15 and imprinting defect (ID). DNA methylation analysis is the only technique that will diagnose PWS caused by all three genetic mechanisms as well as differentiate PWS from Angelman syndrome (AS) in deletion cases [Glenn et al 1996, Kubota et al 1996, Glenn et al 1997]. See Table 1 for a summary of molecular genetic testing used to define the underlying genetic mechanism in a proband. The main molecular mechanisms are further classified by specific genetic etiology into molecular class Ia-IIIb, which is important for genetic counseling (see Table 3). See Figure 1 for a comprehensive testing strategy to establish the genetic mechanism of an individual with DNA methylation analysis consistent with PWS. #### Figure 1. Comprehensive testing strategy to establish the molecular class of PWS FISH = fluorescence in situ hybridization Note: A DNA methylation analysis consistent with PWS is sufficient for clinical diagnosis but not for genetic counseling, which requires identification of the underlying genetic mechanism (Table 1). See Genetic Counseling. ### Table 1. Testing Used in Prader-Willi Syndrome View in own window MethodGenetic Mechanisms Detected 1Proportion of PWS Detected by Method DNA methylation 2Deletions, UPD & ID>99% MS-MLPA 3Deletions, UPD & ID>99% FISH 4Deletions65%-75% CMA 5Deletions65%-75% CMA-SNP array 6Deletions & some UPDs80%-90% DNA polymorphisms 7UPD and ID20%-30% DNA sequence 8ID with IC deletions<1% IC = imprinting center; ID = imprinting defect; UPD = uniparental disomy 1\. See Molecular Genetics for more details. 2\. Can establish diagnosis, but will not distinguish genetic mechanism; can be done by Southern blot or methylation-specific PCR. 3\. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA): • Will distinguish deletion from disomy (UPD and ID); • Will not distinguish UPD from ID; • Can give approximate size of deletion and identify type 1 and 2 deletions (see Figure 2); • Can also detect most IC and SNORD116 microdeletions (see Figure 2 and Molecular Pathogenesis). 4\. FISH is typically done in conjunction with a karyotype. Information is limited to AS/PWS region and the specific probes used (e.g., SNRPN). FISH does not query the whole AS/PWS region and will miss small deletions. It does not give information about the rest of the chromosomes, and does not distinguishbetween normal, UPD, and ID. 5\. Chromosomal microarray (CMA) has a slightly higher detection frequency than FISH and will provide detailed information regarding size of the deletion. Also, it gives information regarding deletions and duplication in the remainder of the genome. CMA is far more precise than karyotype and FISH; it will detect SNORD116 microdeletions (see Figure 2 and Molecular Pathogenesis). 6\. Same as CMA; in addition, use of small nucleotide polymorphisms (SNP) will allow detection of UPD in cases with long stretches of homozygosity. 7\. Not a first line test; performed after DNA methylation analysis diagnoses PWS, but FISH or CMA analysis indicates disomy. 8\. DNA sequencing has a very specific role in IDs to distinguish IC deletions from epimutations. It is limited to a region of <4.3 kb in the PWS IC smallest region of deletion overlap (SRO) [Ohta et al 1999]. The map location is approximately 25,196,494 to 25,200,794 bp [UCSC Genome Browser, hg19]. ## Clinical Characteristics ### Clinical Description Perinatal. Fetal size is generally within the normal range. Prenatal hypotonia usually results in decreased fetal movement, abnormal fetal position at delivery, and increased incidence of assisted delivery or cesarean section. Birth weight and body mass index (BMI) are on average 15% less than in normal sibs [Miller et al 2011]. Hypotonia. Infantile hypotonia is a nearly universal finding, causing decreased movement and lethargy with decreased spontaneous arousal, weak cry, and poor reflexes, including poor suck. The hypotonia is central in origin, and neuromuscular studies including muscle biopsy, when done for diagnostic purposes, are generally normal or show nonspecific signs of disuse. The poor suck, lethargy, and poor appetite result in failure to thrive in early infancy, and enteral tube feeding or the use of special nipples is generally required for a variable period of time, usually weeks to months. By the time that the child is drinking from a cup or eating solids, a period of approximately normal eating behavior occurs. The hypotonia improves over time. Adults remain mildly hypotonic with decreased muscle bulk and tone. Developmental delay. Delayed motor development is present in 90%-100% of children with PWS, with average early milestones achieved at about double the normal age (e.g., sitting at 12 months, walking at 24 months). Language milestones are also typically delayed. Intellectual disabilities are generally evident by the time the child reaches preschool age. Testing indicates that most persons with PWS fall in the mildly intellectually disabled range (mean IQ: 60s to 70s), with approximately 40% having borderline disability or low-normal intelligence and approximately 20% having moderate disability. Regardless of measured IQ, most children with PWS have multiple severe learning disabilities and poor academic performance for their intellectual abilities [Whittington et al 2004a]. Although a small proportion of affected individuals have extremely impaired language development, verbal ability is a relative strength for most. Based on the authors' experiences, a small percentage of individuals with PWS are able to attend and graduate from college. Hypogonadism. In both sexes, hypogonadism is present and manifests as genital hypoplasia, incomplete pubertal development, and infertility in the vast majority. Genital hypoplasia is evident at birth and throughout life. * Males. The penis may be small, and most characteristic is a hypoplastic scrotum that is small, poorly rugated, and poorly pigmented. Unilateral or bilateral cryptorchidism is present in 80%-90% of males. * Females. The genital hypoplasia is often overlooked; however, the labia majora and minora and the clitoris are generally small from birth. The hypogonadism is usually associated with low serum concentration of gonadotropins and causes incomplete, delayed, and sometimes disordered pubertal development. Precocious adrenarche occurs in approximately 15%-20%. Infertility is the rule, although a few instances of reproduction in females have been reported [Akefeldt et al 1999; Schulze et al 2001; Vats & Cassidy, unpublished data]. Although the hypogonadism in PWS has long been believed to be entirely hypothalamic in origin, recent studies have suggested a combination of hypothalamic and primary gonadal deficiencies [Eldar-Geva et al 2009, Hirsch et al 2009, Eldar-Geva et al 2010, Gross-Tsur et al 2012], a conclusion largely based on the absence of hypogonadotropism and abnormally low inhibin B levels in some affected individuals of both sexes. In one study of 84 individuals with PWS (half males, half females) age two to 35 years [Crinò et al 2003], the following were identified: * Males. Cryptorchidism 100%, small testes 76%, scrotal hypoplasia 69% * Females. Labia minora and/or clitoral hypoplasia 76%, primary amenorrhea 56%, spontaneous menarche (mostly spotting) 44% of those older than age 15 years * Both sexes. Premature pubarche 14%, precocious puberty 3.6% (1 male, 2 females) Appetite and obesity. In contrast to the long-held view that there are only two distinct nutritional phases in PWS (i.e., failure to thrive followed by hyperphagia leading to obesity) a multicenter study [Miller et al 2011] found that the transition between nutritional phases is much more complex, with seven different nutritional phases through which individuals with PWS typically progress (Table 2). ### Table 2. Nutritional Phases in PWS View in own window PhaseMedian AgesClinical Characteristics 0Prenatal - birthDecreased fetal movements & lower birth weight than sibs 1a0-9 monthsHypotonia with difficulty feeding & decreased appetite 1b9-25 monthsImproved feeding & appetite; growing appropriately 2a2.1-4.5 yearsWeight increasing without appetite increase or excess calories 2b4.5-8 yearsIncreased appetite & calories, but can feel full 38 years - adulthoodHyperphagic, rarely feels full 4AdulthoodAppetite no longer insatiable for some Miller et al [2011] The hyperphagia that occurs in PWS is believed to be caused by a hypothalamic abnormality resulting in lack of satiety. Food-seeking behavior, with hoarding or foraging for food, eating of inedibles, and stealing of food or money to buy food, are common. In most, gastric emptying is delayed, and vomiting is rare. Obesity results from these behaviors and from decreased total caloric requirement. The latter is due to decreased resting energy expenditure resulting from decreased activity and decreased lean body mass (primarily muscle) compared with unaffected individuals. The obesity in PWS is primarily central (abdomen, buttocks, and thighs) in both sexes, and interestingly, there is less visceral fat in obese individuals than would be expected for the degree of obesity. Obesity and its complications are the major causes of morbidity and mortality (see Morbidity and mortality). Several independent groups have shown that ghrelin levels are significantly elevated in hyperphagic older children and adults with PWS before and after meals [Cummings et al 2002, DelParigi et al 2002, Haqq et al 2003b]. Ghrelin is a potent circulating orexigenic hormone that is produced mainly in the stomach. Circulating ghrelin levels rise after fasting and are suppressed by food intake. The appetite-inducing effect acts through the appetite regulating pathway in the hypothalamus. Ghrelin levels are lower in non-PWS obese individuals than in lean controls, and they decrease with age [Scerif et al 2011]. A small study of nine non-hyperphagic children with PWS (age 17-60 months) found similar levels of circulating ghrelin as in the eight control children matched for BMI, age, and sex [Erdie-Lalena et al 2006]. By contrast, in two much larger and younger study cohorts of children and adolescents with PWS ghrelin levels were significantly elevated in the PWS group at any age compared to controls [Feigerlová et al 2008, Kweh et al 2015]. In fact, the highest ghrelin levels in PWS were found in the youngest children. Thus, in these two large studies the hyperghrelinemia occurred at an age long before the development of obesity and increased appetite in PWS. Furthermore, several groups have now shown that pharmacologic reduction of ghrelin to normal levels in PWS, using either short- or long-acting agents, did not affect the weight, appetite, or eating behavior in hyperphagic individuals [Haqq et al 2003a, Tan et al 2004, De Waele et al 2008]. At this time there are no consistently identified hormonal abnormalities to explain the hyperphagia, and the metabolic correlates of hyperphagia in PWS remain uncertain. Endocrinologic concerns. Up to 25% of adults with PWS (particularly those with significant obesity) have type 2 diabetes [Butler et al 2002] with a mean age of onset of 20 years. In the last 15 years, earlier diagnosis and education of parents, use of growth hormone therapy, and the frequency of group homes specific for PWS have led to reduction in the development of morbid obesity (and as a result, in type 2 diabetes) among individuals with PWS. Central hypothyroidism, with a normal thyroid-stimulating hormone value and low free thyroxine level, has been documented in up to 25% of individuals with PWS, with a mean age of diagnosis and treatment of two years [Miller et al 2008, Diene et al 2010]. Central adrenal insufficiency (CAI) following overnight single-dose metyrapone tests was noted in 60% of children with PWS in one study, suggesting that this may be the cause of the high incidence of sudden death in this population [de Lind van Wijngaarden et al 2008]. It is known that introducing GH therapy can precipitate adrenal crisis in individuals with incipient adrenal insufficiency by accelerating the peripheral metabolism of cortisol, which may explain the correlation between the incidence of sudden death at the beginning of GH treatment and CAI in individuals with PWS [Scaroni et al 2008]. However, subsequent studies have found normal cortisol responses to low- and high-dose synacthen testing, as well as to insulin tolerance testing [Nyunt et al 2010, Farholt et al 2011]; thus, whether CAI is a true issue for individuals with PWS remains uncertain at this time and no consensus exists among endocrinologists as to whether evaluation for CAI should be performed on every individual with PWS or only those with symptoms consistent with adrenal insufficiency. Sleep abnormalities are well documented and include reduced REM (rapid eye movement) latency, altered sleep architecture, oxygen desaturation, and both central and obstructive apnea [Festen et al 2006, Priano et al 2006]. Primary hypothalamic dysfunction is thought to be the cause of the alterations in sleep microstructure and abnormalities in ventilation during sleep, with studies showing low levels of orexin and hypocretin in the cerebrospinal fluid and decreased levels of acetyl-cholinergic neurons in the pedunculo-pontine tegmental nucleus [Dauvilliers et al 2003, Nevsimalova et al 2005, Bruni et al 2010, Hayashi et al 2011]. Some individuals with PWS have excessive daytime sleepiness, which resembles narcolepsy, with rapid onset of REM sleep and decrease in non-REM sleep instability [Bruni et al 2010]. Behavior. A characteristic behavior profile with temper tantrums, stubbornness, controlling and manipulative behavior, compulsivity, and difficulty with change in routine becomes evident in early childhood in 70%-90% of individuals with PWS. * Many of the behavioral characteristics are suggestive of autism; one study showed that 19% of 59 individuals with PWS versus 15% of age-, sex-, and IQ-matched controls satisfy diagnostic criteria for autism [Descheemaeker et al 2006]. * In another study of 58 children, attention deficit/hyperactivity symptoms and insistence on sameness were common and of early onset [Wigren & Hansen 2005]. * This behavior disorder has been reported to increase with age and body mass index (BMI) [Steinhausen et al 2004], although it diminishes considerably in older adults [Dykens 2004]. * Psychosis is evident by young adulthood in 10%-20% of affected individuals, and is more frequent in those with UPD [Boer et al 2002, Clarke et al 2002, Vogels et al 2004, Yang et al 2013]. Behavioral and psychiatric problems interfere most with the quality of life in adolescence and adulthood. Growth. Short stature, if not apparent in childhood, is almost always present during the second decade in the absence of growth hormone (GH) replacement, and lack of a pubertal growth spurt results in an average untreated height of 155 cm for males and 148 cm for females. The hands and feet grow slowly and are generally below the fifth centile by age ten years, with an average adult female foot size of 20.3 cm and average adult male foot size of 22.3 cm. Growth charts for affected infants and children not treated with growth hormone have been published [Butler et al 2011, Butler et al 2015] and growth charts for growth hormone-treated children with PWS have been developed [MG Butler & DJ Driscoll, unpublished data]. Data from at least 15 studies involving more than 300 affected children [Burman et al 2001] document reduced GH secretion in PWS. GH deficiency is also seen in adults with PWS [Grugni et al 2006, Höybye 2007]. Dysmorphic features. Characteristic facial features (narrow bifrontal diameter, almond-shaped palpebral fissures, narrow nasal bridge, thin vermilion of the upper lip with down-turned corners of the mouth) may or may not be apparent at birth and slowly evolve over time. Hypopigmentation of hair, eyes, and skin is frequently found in patients with a deletion due to loss of a single copy of the gene OCA2. Ophthalmic issues. Strabismus is seen in 60%-70%. Skeletal findings. Hip dysplasia occurs in approximately 10%-20% [West & Ballock 2004, Shim et al 2010]. Bone fractures are a risk due to the increased frequency of osteopenia and osteoporosis. Scoliosis, present in 40%-80%, varies in age of onset and severity. Other. Rates of the following are increased: * Possibility of recurrent respiratory infections (in ≤50% of individuals) * Leg edema and ulceration (especially in the obese) * Skin picking * Altered temperature sensation * Decreased saliva flow * High vomiting threshold * Seizures (in 10%-20%) Morbidity and mortality. Mortality rate in PWS is higher than in controls with intellectual disability, with obesity and its complications being factors [Einfeld et al 2006]. Based on a population study, the death rate was estimated at 3% per year [Butler et al 2002], although a later study of the same population showed the rate to be decreasing to 1.25% per annum with improved management [Whittington et al 2015]. Two multicenter series of individuals who died of PWS have been reported [Schrander-Stumpel et al 2004, Stevenson et al 2004], and an extensive case and literature review of 64 cases of death in PWS was performed [Tauber et al 2008]. Respiratory and other febrile illnesses were the most frequent causes of death in children, and obesity-related cardiovascular problems and gastric causes or sleep apnea were most frequent in adults. Other causes of morbidity include diabetes mellitus, thrombophlebitis, and skin problems (e.g., chronic edema, infection from skin picking). A few individuals have been reported to have respiratory or gastrointestinal infections resulting in unexpected death; of these, three who died as a result were noted to have small adrenal glands [Stevenson et al 2004], although this is not a common finding. The report of central adrenal insufficiency (CAI) in 60% of tested individuals [de Lind van Wijngaarden et al 2008] suggests a possible explanation for some of these unexpected and sudden deaths. Other studies have not demonstrated a high incidence [Farholt et al 2011, Grugni et al 2013] of CAI in PWS. Acute gastric distention and necrosis have been reported in a number of individuals with PWS [Stevenson et al 2007a], particularly following an eating binge among those who are thin but were previously obese. It may be unrecognized because of high pain threshold and can be fatal. Choking, especially on hot dogs, has been reported as cause of death in approximately 8% of deaths in individuals with PWS [Stevenson et al 2007b]. Concern about the possible contribution of growth hormone (GH) administration to unexpected death has been raised by reported deaths of individuals within a few months of starting GH therapy [Eiholzer 2005, Sacco & Di Giorgio 2005]. The few reported deaths were mostly in obese individuals who had pre-existing respiratory or cardiac disorders with evidence of upper airway obstruction and uncorrected tonsillar and adenoidal hypertrophy. In the database of one pharmaceutical company, five of 675 children treated with GH died suddenly of respiratory problems [Craig et al 2006]. In another study, the rate of death in affected individuals on and off GH did not differ [Nagai et al 2005]. A study of the natural history of PWS in one region of the UK found the overall death rate of individuals with PWS to be as high as 3% per year without GH therapy [Whittington et al 2001]. Thus, the relationship of GH administration to unexpected death remains unclear. However, it is advisable to obtain a sleep study before the initiation of GH therapy and again four to eight weeks after the beginning of GH therapy to ensure that GH treatment has not caused or worsened sleep-disordered breathing [Miller et al 2006b]. A long-term study of 48 treated children suggests that the benefits of treatment with GH greatly exceed the risks [Carrel et al 2010]. Neuroimaging. In one study, all 20 individuals with PWS who were evaluated had brain abnormalities that were not found in 21 sibs or 16 individuals with early-onset morbid obesity who did not have PWS [Miller et al 2007]. All had ventriculomegaly; 50% had decreased volume of brain tissue in the parietal-occipital lobe; 60% had Sylvan fissure polymicrogyria; and 65% had incomplete insular closure. In another study, these authors reported white matter lesions in some people with PWS [Miller et al 2006a]. A study of brain MRIs from 91 individuals with PWS from another group showed reduced pituitary height in 49% and some neuroradiologic abnormality in 67% [Iughetti et al 2008]. The implications of these findings are unknown. ### Genotype-Phenotype Correlations No phenotypic feature is known to correlate exclusively with any one of the three main molecular mechanisms that result in PWS. However, some statistical differences in the frequency or severity of certain features between the two largest molecular classes (deletion and UPD) are observed. UPD * Post-term delivery is more common with UPD [Butler et al 2009]. * Individuals with UPD are less likely to have the typical facial appearance, hypopigmentation, or skill with jigsaw puzzles [Dykens 2002]; they also have a somewhat higher verbal IQ and milder behavior problems [Dykens et al 1999, Roof et al 2000, Hartley et al 2005]. * Individuals with UPD are more likely to have psychosis [Holland et al 2003, Yang et al 2013] and autism spectrum disorders [Veltman et al 2004, Whittington et al 2004b, Veltman et al 2005, Descheemaeker et al 2006]. Studies suggest that as many as 62% of those with UPD develop atypical psychosis compared with 16% of those with a deletion [Soni et al 2007]. Deletion * Individuals with a deletion showed a higher frequency of need for special feeding techniques, sleep disturbance, hypopigmentation, and speech articulation defects in a recent study of 91 children [Torrado et al 2007]. * Individuals with the slightly larger, type 1 deletions (BP1 to BP3; see Figure 2) have been reported to have more compulsions and poorer adaptive behavior, intellectual ability, and academic achievement than those with type 2 deletions (BP2 to BP3) [Butler et al 2004, Hartley et al 2005]. Two other studies found much less clinically significant differences between individuals with these two deletion types [Milner et al 2005, Varela et al 2005]. Larger studies are needed to determine whether there are significant clinical differences between the two most frequent deletion classes. #### Figure 2. Summary of the genetic and expression map of chromosome region 15q11.2-q13 The Prader-Willi syndrome (PWS) region (shown in blue) has five paternal-only (PWS region) expressed unique-copy genes that encode polypeptides (MKRN3, MAGEL2, NECDIN, and SNURF-SNRPN) (more...) ### Penetrance Penetrance is complete. ### Nomenclature The term HHHO (hypogonadism, hypotonia, hypomentia, obesity) is no longer used. The condition is sometimes called Willi-Prader syndrome or Prader-Labhart-Willi syndrome. ### Prevalence The estimated prevalence of PWS is 1:10,000 to 1:30,000 in a number of populations. ## Differential Diagnosis Many disorders can mimic parts of the PWS phenotype. Craniopharyngioma and the results of its treatment show the greatest overlap with PWS. Damage to the hypothalamus causes most of the same findings that characterize PWS, particularly when craniopharygioma occurs at an early age. History and, if uncertain, DNA methylation analysis will distinguish craniopharyngioma from PWS. Hyperphagic short stature is an acquired condition related to psychosocial stress that includes growth hormone insufficiency, hyperphagia, and mild learning disabilities [Gilmour et al 2001]. History and, if uncertain, DNA methylation analysis should distinguish this disorder from PWS. Hypotonia in infancy is also seen in the following conditions: * Neonatal sepsis * Central nervous system depression * Congenital myotonic dystrophy type 1, characterized by hypotonia and severe generalized weakness at birth, often with respiratory insufficiency and early death; intellectual disability is common. It is caused by expansion of a CTG trinucleotide repeat in DMPK. * Several myopathies and neuropathies, including some instances of spinal muscular atrophy (SMA) [Miller et al 1999, Richer et al 2001]. In these situations, poor respiratory effort may be present, a feature rarely seen in PWS. Molecular genetic testing, EMG/NCV, and/or muscle biopsy are often required to differentiate these conditions. * Angelman syndrome (AS), characterized by severe developmental delay or intellectual disability, severe speech impairment, gait ataxia and/or tremulousness of the limbs, and a unique behavior with an inappropriate happy demeanor that includes frequent laughing, smiling, and excitability. Microcephaly and seizures are also common. AS is caused by deficient expression or function of the maternally inherited UBE3A allele and may be diagnosed in 75%-80% of individuals with AS using DNA methylation analysis of chromosome 15. In infancy, hypotonia may be the only manifestation of AS. Affected individuals lack the characteristic sucking problems, hypogonadism, and facial appearance of individuals with PWS. * Fragile X syndrome, characterized by moderate intellectual disability in affected males and mild intellectual disability in affected females. Males may have a characteristic appearance (large head, long face, prominent forehead and chin, protruding ears), connective tissue findings (joint laxity), and large testes (postpubertally). Behavioral abnormalities, sometimes including autism spectrum disorder, are common. The diagnosis of fragile X syndrome rests on the detection of an alteration in FMR1 consisting of expansion of a triplet repeat and aberrant gene methylation. In infancy, hypotonia may be the only manifestation. Affected individuals lack the characteristic sucking problems, hypogonadism, and facial appearance of individuals with PWS. * WAC-related intellectual disability is typically characterized by variable degrees of global developmental delay and/or intellectual disability. Behavioral abnormalities including anxiety, attention deficit/hyperactivity disorder, and/or autism spectrum disorder are observed in the majority of older children and adults. Most affected infants have significant but nonspecific features at birth such as neonatal hypotonia and feeding problems. Some affected individuals come to medical attention with respiratory or vision problems. Facial features may be mildly dysmorphic, but are nonspecific. To date, 18 individuals have been identified with WAC-related ID. The diagnosis of WAC-related ID is established in a proband by identification of a heterozygous pathogenic variant in WAC on molecular genetic testing. Developmental delay/intellectual disability and obesity with or without hypogonadism can be seen in the following disorders: * Angelman syndrome (AS). Individuals with AS caused by paternal UPD 15 frequently have an elevated BMI for age. In one large study overweight was found in more than 70% and obesity in more than 40% [Lossie et al 2001]. * Fragile X syndrome. A subset have been found with a "Prader-Willi-like" phenotype including hyperphagia and obesity [de Vries et al 1993]. * Maternal uniparental disomy for chromosome 14, which also includes prenatal growth retardation, feeding problems, short stature, and precocious puberty [Cox et al 2004, Hosoki et al 2009] * Albright hereditary osteodystrophy (OMIM 103580), which also includes short stature, but lacks hypotonia and has different characteristic facial appearance (round face). Specific testing is possible by measurement of Gs receptor-coupling protein. * Bardet-Beidl syndrome (BBS), characterized by cone-rod dystrophy, truncal obesity, postaxial polydactyly, cognitive impairment, male hypogonadotropic hypogonadism, complex female genitourinary malformations, and renal dysfunction. Individuals with BBS have a different facial phenotype from those with PWS. Inheritance is typically autosomal recessive, although in fewer than 10% of individuals inheritance may be more complex. * Cohen syndrome, characterized by failure to thrive in infancy and childhood; truncal obesity in the teen years; early-onset hypotonia and developmental delays; microcephaly developing during the first year of life; moderate to profound psychomotor retardation; progressive retinochoroidal dystrophy and high myopia; neutropenia in many with recurrent infections and aphthous ulcers in some; a cheerful disposition; joint hypermobility; and characteristic facial features which are different from PWS. Cohen syndrome is caused by pathogenic variants in VPS13B. Inheritance is autosomal recessive. * Borjeson-Forssman-Lehmann syndrome (OMIM 301900), seen in males, characterized by severe cognitive deficit, epilepsy, hypogonadism, hypometabolism, marked obesity, infantile hypotonia and failure to thrive, and short stature. It can be distinguished by the severity of intellectual disability, the presence of nystagmus, and characteristic facial appearance with prominent superciliary ridges, ptosis, and deep-set eyes. Pathogenic variants in PHF6 are causative. Inheritance is X-linked. Heterozygous females who show manifestations of the disorder have skewed X-chromosome inactivation or a genomic deletion including PHG6. * Alstrom syndrome, characterized by cone-rod dystrophy, early-onset obesity, progressive sensorineural hearing impairment, dilated cardiomyopathy (>60%), the insulin resistance syndrome/type 2 diabetes mellitus associated with acanthosis nigricans, and developmental delay (~50%). Other endocrine abnormalities can include hypothyroidism and male hypogonadotropic hypogonadism. Urologic disorders of varying severity, characterized by detrusor-urethral dyssynergia, appear in females in their late teens. Severe renal disease is usually a late finding. Pathogenic variants in ALMS1 are found in 70%-80% of individuals of northern European descent, and about 40% of affected individuals worldwide. Cytogenetic abnormalities with a similar phenotype include the following: * A "PWS-like phenotype" of syndromic obesity has been identified in individuals with an interstitial deletion of 6q16.2, which includes SIM1 [Varela et al 2005]. This deletion had been reported at least five times previously in syndromic obesity [Bonaglia et al 2008] as well a duplication [Desch et al 2015]. Also, pathogenic variants in SIM1 alone have been found in patients with severe obesity [Bonnefond et al 2013, Ramachandrappa et al 2013]. * Several reports have associated a Prader-Willi-like phenotype with 1p36 deletion; additional findings include hypotonia, developmental delay, obesity, hyperphagia, and behavioral problems [Tsuyusaki et al 2010, Stagi et al 2014]. * Multiple reports describe deletions at 16p11.2 including SHB2B1, which is involved in leptin and insulin signaling [Maillard et al 2015]. * Reports of other cytogenetic anomalies in individuals with a PWS-like phenotype have included dupXq27.2-ter and del10q26 [Lukusa & Fryns 2000, Ben-Abdallah-Bouhjar et al 2012, Rocha & Paiva 2014]. ## Management Management of the manifestations of Prader-Willi syndrome (PWS) is age dependent and should include both addressing of the consequences of PWS and anticipatory guidance. It is recommended that a team approach be used, if possible. Several approaches to management have been published [Goldstone et al 2008, Cassidy & Driscoll 2009, Cassidy & McCandless 2010, McCandless 2011, Cassidy et al 2012]. ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with PWS, the following evaluations are recommended: * Consultation with a clinical geneticist and/or genetic counselor * Endocrinology consultation * Nutritional consultation * Assessment of newborns and young infants for sucking problems and failure to thrive * Regardless of age, measurement and plotting of height, weight, head circumference and body mass index (BMI) on either age-appropriate growth charts or charts developed for PWS [Butler et al 2011, Butler et al 2015] * Assessment for hypothyroidism in children, especially those with prolonged failure to thrive, those with excess weight gain in the absence of increased food intake, and those with poor linear growth despite growth hormone treatment * Evaluation of respiratory status with a low threshold for performing a sleep study regardless of age. These studies are specifically recommended prior to the initiation of growth hormone therapy (GHT) and four to eight weeks after starting GHT, along with assessment of the size of tonsils and adenoids, particularly in the obese individual. * Assessment of development of infants and of educational development of children including a speech evaluation * Assessment for the presence of behavioral problems and obsessive-compulsive features after age two years, and for psychosis in adolescents and adults. If history reveals evidence of these problems, referral for more detailed assessment is indicated. * Assessment of males for the presence of cryptorchidism regardless of age * Referral for ophthalmologic evaluation if strabismus is present, and for assessment of visual acuity by age one year or at diagnosis if it is later * Regardless of age, assessment for the presence of scoliosis clinically, and, if indicated, radiographically Note: Very obese individuals cannot be adequately assessed for scoliosis clinically; x-rays are necessary to establish the diagnosis. ### Treatment of Manifestations A team approach to management is recommended [Goldstone et al 2008, Cassidy & McCandless 2010]. Feeding, hyperphagia, and obesity. Special feeding techniques, including special nipples or gavage feeding, may be necessary for the first weeks to months of life to assure adequate nutrition and avoid failure to thrive. Individuals diagnosed with PWS typically do not need a G-tube since the feeding will improve with time. When weight centiles begin increasing in nutritional phase 2a (typically between 18 and 36 months), a program of a well-balanced, low-calorie diet, regular exercise, and close supervision to minimize food stealing should be instituted to prevent obesity (i.e., BMI Z score of <2) and its consequences. The same program is appropriate if obesity is present at any time. Consultation with a dietician and close follow up are usually necessary, and locking the kitchen, refrigerator, and/or cupboards is often needed once the child is able to open the refrigerator and cupboards. Caloric needs of infants and children with PWS are typically 60%-80% of the recommended daily allowance (RDA). The energy requirement of adults with PWS, which rarely exceeds 1200-1400 Kcal/day, should be considered in planning daily food intake. Assessment of adequacy of vitamin and mineral intake by a dietician, and prescription of appropriate supplementation, is indicated, especially for calcium and vitamin D. No medications are known to aid in controlling hyperphagia, but several clinical trials are underway (see Therapies Under Investigation). Gastric bypass is not recommended in PWS, as it does not appear to correct the lack of satiety and will not prevent overeating. In addition, complication rates are high [Scheimann et al 2012]. Growth hormone treatment normalizes height, increases lean body mass, decreases fat mass, and increases mobility, which are beneficial to weight management. Dose recommendations in young children are generally similar to those for individuals with isolated growth hormone deficiency (i.e., ~1 mg/m2/day) but the dose must be individualized as the child grows. Therapy can be started in infancy or at the time of diagnosis. The adult dose of growth hormone is 20%-25% of the dose recommended in children. Monitoring of growth velocity, head circumference, and serum IGF-1 is important to avoid overtreatment. Controlled trials of growth hormone therapies have demonstrated significant benefit from infancy through adulthood [Carrel et al 2010, Sode-Carlsen et al 2010, Wolfgram et al 2013]. * An increase in language and cognitive skills in treated infants [Myers et al 2007] and an improvement in mental speed and flexibility as well as motor performance in adults [Höybye et al 2005] have been reported based on controlled trials. * A review of the results of one to two years of growth hormone treatment among 328 children documented in the database of one pharmaceutical company indicated improved height velocity, particularly in prepubertal children, but no change in BMI [Craig et al 2006]. * Significantly greater adult height was demonstrated in 21 individuals treated long term versus 39 untreated individuals without an increase in adverse side effects [Angulo et al 2007]. * Some improvements in cognition have been suggested with growth hormone therapy in individuals with PWS [Osório 2012, Siemensma 2012], but more work and longer studies need to be done. * Although there was initial concern about growth hormone treatment contributing to scoliosis in PWS, later studies showed no difference in frequency or severity in those treated compared to those who were not treated [Nagai et al 2006, Angulo et al 2007]. Decreased saliva production can be addressed with products developed for the treatment of dry mouth, including special toothpastes, gels, mouthwash, and gum. Therapies, education and behavior management. Early intervention in children before age three years, particularly physical therapy, may improve muscle strength and encourage achievement of developmental milestones. In older individuals, daily muscle training increases physical activity and lean body mass [Schlumpf et al 2006]. Initiate appropriate educational programming in children: * Begin speech therapy for language delay and articulation abnormalities in infancy and childhood. * Special education, either in an inclusion setting or in a self-contained classroom setting, is usually necessary during school age. An individual aide is helpful in assuring attendance to task. Social skills training groups have been beneficial. Behavioral disturbance should be addressed with behavioral management programs, including firm limit setting. While no medication is beneficial in managing behavior in all individuals with PWS, serotonin reuptake inhibitors have helped the largest proportion of affected teenagers and adults, particularly those with obsessive-compulsive symptoms [Brice 2000, Dykens & Shah 2003]. Psychosis is reported to respond well to selective serotonin reuptake inhibitors, but not to mood stabilizers [Soni et al 2007]. There are no well-designed studies of the effectiveness of treatment for psychosis in PWS [Ho & Dimitropoulos 2010]. Hypogonadism. Cryptorchidism may resolve spontaneously, even up to adolescence, but usually requires hormonal and surgical approaches; however, preservation of fertility is not an issue. Standard treatment is appropriate. Human chorionic gonadotropin treatment for infants with undescended testes should be considered as it can improve the size of the scrotal sac and improve surgical outcome [McCandless 2011; Angulo & Miller, unpublished data]. Replacement of sex hormones produces adequate secondary sexual characteristics but is somewhat controversial because of the possible role of testosterone replacement in behavior problems in males and the role of estrogen replacement in the risk of stroke as well as hygiene concerns related to menstruation in females. Daily use of the testosterone patch or gel may avert exacerbation of behavioral problems by providing a more even blood level than use of a slow-release depo-testosterone injection every month. Also, it was shown in the non-PWS adult population that depo- testosterone injections were associated with a greater risk of cardiovascular events, hospitalizations, and deaths compared with gels and patches [Layton et al 2015]. Concern about osteoporosis should be considered in deciding about hormone replacement. Recent reports of fertility in four women with PWS raise the issue of need for birth control [Akefeldt et al 1999; Schulze et al 2001; Vats & Cassidy, unpublished data]. Sleep issues. Disturbed sleep in children and adults should prompt a sleep study, as treatment may be available. Treatment depends on the cause and may include tonsillectomy and adenoidectomy and/or CPAP or BiPAP, as in the general population. Excessive daytime sleepiness (unrelated to the degree of sleep apnea) is frequently seen in individuals with PWS. Modafinil has been shown to be a safe and effective treatment for this condition [De Cock et al 2011]. Skin picking. One study demonstrated decreased skin picking with topiramate treatment in some individuals [Shapira et al 2004]; other clinicians have reported anecdotally that approximately half of individuals with PWS who skin pick benefit from low-dose (25-50 mg daily) topiramate. A recent study of 35 individuals with PWS (age 5-39 years) using 450-1200 mg/day of N-acetylcysteine found a high degree of success in reducing or eliminating skin picking [Miller & Angulo 2014]. Other * Management of strabismus is as for any infant. * Management of scoliosis, hip dysplasia, and complications of obesity is as in the general population. Adulthood. For adults with PWS, the most successful living situation for behavior and weight management is a group home specially designated for individuals with PWS, where diet and access to food are tightly restricted and exercise is included in daily activities. Affected individuals generally require a sheltered employment environment. Issues of guardianship, wills, trusts, and advocacy should be investigated no later than adolescence. ### Prevention of Primary Manifestations Obesity may be prevented if the diet, exercise, and supervision program described in Treatment of Manifestations is instituted. Early diagnosis allows the clinician to begin anticipatory guidance concerning the natural history of PWS, and in particular the nutritional phases, informing the family about the risk of obesity and the need to monitor weight increase and to restrict calories beginning around 18-36 months of age. If started at a young age, growth hormone treatment, along with good dietary control, may retard obesity and the high proportion of fat mass. It may also prevent development of the typical facial appearance and improve motor milestones. ### Prevention of Secondary Complications Diabetes mellitus rarely occurs in the absence of obesity. Calcium and vitamin D supplementation are probably beneficial, as low-calorie diets are often low in dairy products and osteoporosis has been documented in the majority of older children and adults with PWS. If osteoporosis develops, consider treatment with a bisphosphonate. Although no formal study exists, individuals with PWS tend to be very sensitive to medications of all kinds. Starting with lower doses is recommended. ### Surveillance Health supervision guidelines from the American Academy of Pediatrics (AAP) have been published [McCandless 2011] (full text). To assure appropriateness of exercise program and diet, including adequacy of vitamin and mineral intake and monitor height, weight, and BMI (weight in kg/height in m2): * Every month in infancy; * Every six months in the first decade of life; * At least annually thereafter. Cryptorchidism can recur after orchidopexy; therefore, testicular position should be monitored. Evaluate for the presence of diabetes mellitus by standard methods (e.g., obtaining glycosylated hemoglobin concentration and/or glucose tolerance test) in anyone with significant obesity or rapid significant weight gain. Test annually for hypothyroidism, including free T4 and TSH levels. Obtain history of any sleep disturbance; if present, obtain a sleep study. Monitor for development of scoliosis clinically or, in the presence of obesity, radiographically at least annually. Perform bone densitometry by DEXA to evaluate for possible osteoporosis every two years in adulthood. Obtain history for behavioral and psychiatric disturbance at least annually. ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation In the last few years there has been great interest by the pharmaceutical industry in testing treatments for the major manifestations of PWS – particularly the hyperphagia, obesity, and behavioral problems. For a detailed description of these studies, click here (pdf). 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	Prader-Willi Syndrome	c0032897	25,030	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1330/	2021-01-18T21:02:41	{"mesh": ["D011218"], "synonyms": ["Prader-Labhart-Willi Syndrome", "PWS"]}
Severe generalized recessive dystrophic epidermolysis bullosa is the most severe types of dystrophic epidermolysis bullosa. The signs and symptoms of this condition involve widespread blistering that can lead to vision loss, disfigurement, and other serious medical problems. As the blisters heal, they result in severe scarring. Scarring in the mouth and esophagus can make it difficult to eat food, leading to poor nutrition and slow growth. Additionally, individuals with this condition have a very high risk of developing a form of skin cancer called squamous cell carcinoma, which tends to be unusually aggressive and is often life-threatening. Severe generalized recessive dystrophic epidermolysis bullosa is caused by mutations in the COL7A1 gene and is inherited in an autosomal recessive pattern. There is no cure for this condition and treatment is aimed at preventing blisters from forming and managing 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	Severe generalized recessive dystrophic epidermolysis bullosa	c0079474	25,031	gard	https://rarediseases.info.nih.gov/diseases/6308/severe-generalized-recessive-dystrophic-epidermolysis-bullosa	2021-01-18T17:57:45	{"mesh": ["D016108"], "omim": ["226600"], "orphanet": ["79408"], "synonyms": ["RDEB, severe generalized", "Autosomal recessive dystrophic epidermolysis bullosa, Hallopeau-Siemens type", "Autosomal recessive dystrophic epidermolysis bullosa, Hallopeau-Siemens type (formerly)", "Recessive dystrophic epidermolysis bullosa, severe generalized", "RDEB-sev gen", "RDEB, Hallopeau-Siemens type", "Autosomal recessive dystrophic epidermolysis bullosa generalisata gravis", "RDEB generalisata gravis", "Severe generalized RDEB"]}
Human disease Cavernous hemangioma Micrograph of a cavernous liver hemangioma. H&E stain. SpecialtyOncology, hematology, cardiology, neurosurgery Cavernous hemangioma, also called cavernous angioma, cavernoma, or cerebral cavernoma (CCM) (when referring to presence in the brain)[1][2] is a type of benign vascular tumor or hemangioma, where a collection of dilated blood vessels form a lesion. The abnormal tissue causes a slowing of blood flow through the cavities, or "caverns". The blood vessels do not form the necessary junctions with surrounding cells, and the structural support from the smooth muscle is hindered, causing leakage into the surrounding tissue. It is the leakage of blood, referred to as hemorrhage, that causes a variety of symptoms known to be associated with the condition. ## Contents * 1 Symptoms * 2 Presentation * 2.1 Causes * 3 Variations * 3.1 Cerebral cavernomas * 3.2 Liver cavernous hemangioma * 3.3 Eye cavernous hemangioma * 4 Mechanism * 5 Diagnosis * 6 Treatment * 6.1 Prognosis * 7 Epidemiology * 8 Research * 9 References * 10 Further reading ## Symptoms[edit] People with this condition in the brain may or may not experience symptoms. Some complications of the condition are life-threatening or cause major disruptions to normal functioning. Dangerous seizures due to compression of the brain, bleeding inside the brain tissue, vision problems, difficulty with speaking or using words, memory loss, ataxia, or hydrocephalus can occur. Less serious symptoms may include headaches and weakness or numbness in the arms or legs, though these symptoms alone do not indicate a person has the condition. In the eye, it may cause disruption or damage to the extraocular muscles and optic nerve which may manifest as double vision, progressive proptosis, decreased visual acuity, or other vision changes. It can lead to partial or complete blindness. When the condition occurs in the liver it usually does not cause symptoms, but some may experience pain in the upper right abdomen, a feeling of fullness after eating only a small amount of food, decreased appetite, nausea, or vomiting.[3][4] ## Presentation[edit] Cavernous hemangiomas can arise nearly anywhere in the body where there are blood vessels. They are sometimes described as resembling raspberries because of the appearance of bubble-like caverns. Unlike capillary hemangiomas, cavernous ones can be life-threatening and do not tend to regress. ### Causes[edit] Most cases of cavernomas are thought to be congenital; however they can develop over the course of a lifetime.[5] While there is no definitive cause, research suggests that genetic mutations result in the condition. Congenital hemangiomas that appear on the skin are known as either vascular or red birthmarks. Familial cerebral cavernous malformations are known to occur. The mutations may be inherited in an autosomal dominant fashion or occur sporadically. Overall, familial disease is thought to be responsible for one-third to one-half of cases.[6] In the US, approximately 50% of Hispanic patients with cerebral cavernous malformations have a familial form. In contrast, the familiar form of the condition accounts for only 10 to 20% of cases in Caucasians.[7] The reason for this difference is not presently known. Several genes – K-Rev interaction trapped 1 (ССМ1), Malcavernin (CCM2) and Programmed cell death protein 10 (ССМ3) – have been identified as having mutations thought to be related to these lesions.[8][9][10] These genes are located at 7q21.2 (chromosome 7 long arm), 7p13 (chromosome 7 short arm)[11] and 3q25.2-q27 (chromosome 3 long arm) respectively. These lesions are further discussed in the Online Mendelian Inheritance in Man site – the reference numbers are OMIM 116860, OMIM 603284 and OMIM 603285 respectively. ## Variations[edit] ### Cerebral cavernomas[edit] Cavernous hemangiomas located in the brain or spinal cord are referred to as cerebral cavernomas or more usually as cerebral cavernous malformations (CCMs),[12][2] and can be found in the white matter, but often abut the cerebral cortex. When they contact the cortex, they can represent a potential seizure focus for the patient. Unlike other cavernous hemangiomas, there is no tissue within the malformation and its borders are not encapsulated. Therefore, they can change in size and number over time.[5] ### Liver cavernous hemangioma[edit] Cavernous hemangiomas are the most common benign tumors of the liver.[13] Usually one tumor exists, but multiple lesions can occur in the left or right lobe of the liver in 40% of patients.[3] Their sizes can range from a few millimeters to 20 centimetres. Those over 5 cm are often referred to as giant hemangiomas.[3] Ultrasound of hemangioma in the liver. ### Eye cavernous hemangioma[edit] In the eye, it is known as orbital cavernous hemangioma and is found in women more frequently than men, most commonly between the ages of 20–40.[14] This neoplasm is usually located within the muscle cone, which is lateral to the optic nerve. It is not usually treated unless the patient is symptomatic. Visual impairment happens when the optic nerve is compressed or the extraocular muscles are surrounded. ## Mechanism[edit] There are several known causes for cavernous hemangiomas, but some cases are still unknown. Radiation treatment used for other medical conditions has been suggested to cause cavernous malformation in some patients.[15] Hemangioma tumors are a result of rapid proliferation of endothelial cells and pericytic hyperplasia, or the enlargement of tissue as a result of abnormal cell division pericytes. The pathogenesis of hemangioma is still not understood. It has been suggested that growth factors and hormonal influences contribute to the abnormal cell proliferation. Cavernous liver hemangiomas are more commonly diagnosed in women who have been pregnant.[4] As a result of this, it is believed that estrogen levels may play a role in the incidence of liver cavernomas. Genetic studies show that specific gene mutations or deletions are causes for the disease. The genes identified for cerebral cavernous hemangiomas (or malformations), are CCM1 (also KRIT1), CCM2 (also MGC4607, malcavernin) and CCM3 (also PDCD10). The loss of function of these genes is believed to be responsible for cerebral cavernous malformations.[16] Furthermore, it is also believed that a "second hit mutation" is necessary for the onset of the disease. This means that having a mutation in one of the two genes present on a chromosome is not enough to cause the cavernous malformation, but mutation of both alleles would cause the malformation. Additionally, research on hemangiomas in general has shown that loss of heterozygosity is common in tissue where hemangioma develops.[17] This would confirm that more than a single allele mutation is needed for the abnormal cell proliferation. KRIT1 has been shown to act as a transcription factor in the development of arterial blood vessels in mice. CCM2 has overlapping structure with CCM1 (KRIT1) and acts as a scaffolding protein when expressed. Both genes are involved with MAP3K3 and thus appear to be a part of the same pathway. A simplified overview of mammalian MAPK pathways CCM2 has been shown to cause embryonic death in mice. Lastly, the CCM3 gene has been shown to have similar expression to CCM1 and CCM2, suggesting a link in its functionality. Currently, no experiments have determined its exact function.[18] The lack of function of these genes in control of a proliferative signaling pathway would result in uncontrolled proliferation and the development of a tumor. In 2018, it was theorized that proliferation of endothelial cells with dysfunctional tight junctions, that are under increased endothelial stress from elevated venous pressure provides the pathophysiological basis for cavernous hemangioma development.[19] ## Diagnosis[edit] Small hemangioma on the scalp of a two-year-old female. Gradient-Echo T2WI magnetic resonance imaging (MRI) is most sensitive method for diagnosing cavernous hemangiomas.[20] MRI is such a powerful tool for diagnosis, it has led to an increase in diagnosis of cavernous hemangiomas since the technology's advent in the 1980s.[15] The radiographic appearance is most commonly described as "popcorn" or "mulberry"-shaped.[21] Computed tomography (CT) scanning is not a sensitive or specific method for diagnosing cavernous hemangiomas.[22] Angiography is typically not necessary, unless it is required to rule out other diagnoses. Additionally, biopsies can be obtained from tumor tissue for examination under a microscope. It is essential to diagnose cavernous hemangioma because treatments for these lesions are less aggressive than that of cancerous tumors, such as angiosarcoma. However, since MRI appearance is practically pathognomonic, biopsy is rarely needed for verification.[22] On ultrasound, cavernous haemangiomas in liver appeared as homogenous, hyperechoic lesions with posterior acoustic enhancement. On CT or MRI scans, it shows peripheral globular/nodular enhancement in the arterial phase, with portions of attenuation of enhancing areas. In the portal venous phase, it shows progressive centripetal enhancement. In delayed phase, it shows retention of contrast. It shows a high signal on T2 weighted images.[23] ## Treatment[edit] Asymptomatic lesions may not require treatment but may need to be monitored for any change in the size. A change in size of lesions in the nose, lips, or eyelids can be treated with steroid drugs to slow its progress. Steroids can be taken orally or injected directly into the tumor. Applying pressure to the tumor can also be used to minimize swelling at the site of the hemangioma. A procedure that uses small particles to close off the blood supply is known as sclerotherapy. This allows for tumor shrinkage and less pain. It is possible for the tumor to regrow its blood supply after the procedure has been done.[24] If the lesion caused by the cavernous hemangioma is destroying healthy tissue around it or if the patient is experiencing major symptoms, then surgery can be used to remove the cavernoma piecemeal.[22] A common complication of the surgery is hemorrhage and the loss of blood. There is also the possibility of the hemangioma reoccurring after its removal.[24] Additionally, the risk of a stroke or death is also possible.[25] Treatments for cerebral cavernous hemangiomas include radiosurgery or microsurgery.[26] The treatment approach depends on the site, size and symptoms present, as well as the history of hemorrhage from the lesion.[26] Microsurgery is generally preferred if the cerebral cavernous hemangioma is superficial in the central nervous system, or the risk of damage to surrounding tissue from irradiation is too high. Additionally, a large hemorrhage with deterioration of the patient or intractable symptoms (such as seizures or coma) are further indications for microsurgical intervention. Gamma-knife radiation is the favored mechanism of radiosurgery. It provides a precise radiation dose to the cerebral cavernous hemangioma while relatively sparing the surrounding tissue.[26] These treatment approaches for cavernous hemangiomas in other regions of the body have limited research. ### Prognosis[edit] A few studies have worked on providing details related to the outlook of disease progression. Two studies show that each year 0.5% of people who have never had bleeding from their brain cavernoma, but had symptoms of seizures, were affected by bleeding.[25] In contrast, patients who have had bleeding from their brain cavernoma in the past had a higher risk of being affected by subsequent bleeding. The statistics for this are very broad, ranging from 4–23% a year.[25] Additional studies suggest that women and patients under the age of 40 are at higher risk of bleeding, but similar conducted studies did not reach the same conclusion.[25] However, when cavernous hemangiomas are completely excised, there is very little risk of growth or rebleeding.[27] In terms of life expectancy, not enough data has been collected on patients with this malformation in order to provide a representative statistical analysis.[15] ## Epidemiology[edit] The true incidence of cavernous hemangiomas is difficult to estimate because they are frequently misdiagnosed as other venous malformations.[28] Cavernous hemangiomas of the brain and spinal cord (cerebral cavernous hemangiomas (malformations) (CCM)), can appear at all ages but usually occur in the third to fourth decade of a person's life with no sexual preference. In fact, CCM is present in 0.5% of the population. However, approximately 40% of those with malformations have symptoms. Asymptomatic individuals are usually individuals that developed the malformation sporadically, while symptomatic individuals usually have inherited the genetic mutation.[5] The majority of diagnoses of CCM are in adults; however, 25% of cases of CCM are children.[5] Approximately 5% of adults have liver hemangiomas in the United States, but most are asymptomatic.[29] Liver hemangiomas usually occur between the ages of 30–50 and more commonly in women.[4] Cases of infantile liver cavernomas are extremely rare. Cavernous hemangioma of the eye is more prevalent in women than men and between the ages of 20–40.[14] ## Research[edit] In the treatment of a brain cavernous hemangioma, neurosurgery is usually the treatment chosen.[30] Research needs to be conducted on the efficacy of treatment with stereotactic radiation therapy, especially on the long-term.[31] However, radiotherapy is still being studied as a form of treatment if neurosurgery is too dangerous due to the location of the cavernoma. Genetic researchers are still working on determining the cause of the illness and the mechanism behind blood vessel formation.[25] Clinical trials are being conducted to better assess when it is appropriate to treat a patient with this malformation and with what treatment method.[15] Additionally, long-term studies are being conducted because there is no information related to the long-term outlook of patients with cavernoma.[32] An existing registry known as The International Cavernous Angioma Patient Registry[33] collects information from patients diagnosed with cavernoma in order to facilitate discovery of non-invasive treatments.[25] ## References[edit] 1. ^ Awad IA, Polster SP (July 2019). "Cavernous angiomas: deconstructing a neurosurgical disease". Journal of Neurosurgery. 131 (1): 1–13. doi:10.3171/2019.3.JNS181724. PMC 6778695. PMID 31261134. 2. ^ a b Algra A, Rinkel GJ (February 2016). "Prognosis of cerebral cavernomas: on to treatment decisions". The Lancet. Neurology. 15 (2): 129–130. doi:10.1016/S1474-4422(15)00340-3. PMID 26654286. 3. ^ a b c Curry MP, Chopra S (2014). "Hepatic Hemangioma". UpToDate. Wolters Kluwer. 4. ^ a b c "Liver Hemangioma". MayoClinic. 2013. 5. ^ a b c d "Cavernous Malformation". Rare Disease Database. National Organization for Rare Disorders, Inc. 6. ^ Mindea SA, Yang BP, Shenkar R, Bendok B, Batjer HH, Awad IA (2006) Cerebral cavernous malformations: clinical insights from genetic studies. Neurosurg Focus; 21(1):e1. 7. ^ Dashti SR, Hoffer A, Hu YC, Selman WR (July 2006). "Molecular genetics of familial cerebral cavernous malformations". Neurosurgical Focus. 21 (1): e2. doi:10.3171/foc.2006.21.1.3. PMID 16859255. 8. ^ Pagenstecher A, Stahl S, Sure U, Felbor U (March 2009). "A two-hit mechanism causes cerebral cavernous malformations: complete inactivation of CCM1, CCM2 or CCM3 in affected endothelial cells". Human Molecular Genetics. 18 (5): 911–8. doi:10.1093/hmg/ddn420. PMC 2640205. PMID 19088124. 9. ^ Bergametti F, Denier C, Labauge P, Arnoult M, Boetto S, Clanet M, et al. (January 2005). "Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations". American Journal of Human Genetics. 76 (1): 42–51. doi:10.1086/426952. PMC 1196432. PMID 15543491. 10. ^ "Entrez Gene: PDCD10 programmed cell death 10". 11. ^ "OMIM Entry * 607929 - CCM2 GENE; CCM2". www.omim.org. Retrieved 2018-05-29. 12. ^ "What is a cavernoma?". Cavernoma Alliance UK. 13. ^ John TG, Greig JD, Crosbie JL, Miles WF, Garden OJ (December 1994). "Superior staging of liver tumors with laparoscopy and laparoscopic ultrasound". Annals of Surgery. 220 (6): 711–9. doi:10.1097/00000658-199412000-00002. PMC 1234471. PMID 7986136. 14. ^ a b Burkat CN, Pargament J, Yen MT, Goel S, Nerad J. "Cavernous hemangioma". EyeWiki. 15. ^ a b c d Salman RA. "Symptomatic brain cavernomas" (PDF). Cavernoma Alliance UK. 16. ^ Mouchtouris N, Chalouhi N, Chitale A, Starke RM, Tjoumakaris SI, Rosenwasser RH, Jabbour PM (2015). "Management of cerebral cavernous malformations: from diagnosis to treatment". TheScientificWorldJournal. 2015: 808314. doi:10.1155/2015/808314. PMC 4300037. PMID 25629087. 17. ^ Marchuk DA (March 2001). "Pathogenesis of hemangioma". The Journal of Clinical Investigation. 107 (6): 665–6. doi:10.1172/jci12470. PMC 208951. PMID 11254664. 18. ^ Mattassi R, Loose DA, Vaghi M (2009). Hemangiomas and Vascular Malformations (PDF). Springer-Verlag Italia. ISBN 978-88-470-0568-6. Archived from the original (PDF) on 2014-04-29. 19. ^ Maish WN (September 2019). "Developmental venous anomalies and brainstem cavernous malformations: a proposed physiological mechanism for haemorrhage". Neurosurgical Review. 42 (3): 663–670. doi:10.1007/s10143-018-1039-9. PMID 30291476. S2CID 52925057. 20. ^ Lehnhardt FG, von Smekal U, Rückriem B, Stenzel W, Neveling M, Heiss WD, Jacobs AH (April 2005). "Value of gradient-echo magnetic resonance imaging in the diagnosis of familial cerebral cavernous malformation". Archives of Neurology. 62 (4): 653–8. doi:10.1001/archneur.62.4.653. PMID 15824268. 21. ^ Wang CC, Liu A, Zhang JT, Sun B, Zhao YL (June 2003). "Surgical management of brain-stem cavernous malformations: report of 137 cases". Surgical Neurology. 59 (6): 444–54, discussion 454. doi:10.1016/s0090-3019(03)00187-3. PMID 12826334. 22. ^ a b c Greenberg MS (2010-01-01). Handbook of neurosurgery. Greenberg Graphics. ISBN 9781604063264. OCLC 892183792. 23. ^ Thampy R, Elsayes KM, Menias CO, Pickhardt PJ, Kang HC, Deshmukh SP, et al. (November 2017). "Imaging features of rare mesenychmal liver tumours: beyond haemangiomas". The British Journal of Radiology. 90 (1079): 20170373. doi:10.1259/bjr.20170373. PMC 5963373. PMID 28766950. 24. ^ a b Miller JM, Morrell N, Quinn RH (August 2018). "Hemangioma". American Academy of Orthopedic Surgeons. 25. ^ a b c d e f "Cavernoma". U.K. National Health Service. 5 February 2019. 26. ^ a b c Poorthuis MH, Klijn CJ, Algra A, Rinkel GJ, Al-Shahi Salman R (December 2014). "Treatment of cerebral cavernous malformations: a systematic review and meta-regression analysis". Journal of Neurology, Neurosurgery, and Psychiatry. 85 (12): 1319–23. doi:10.1136/jnnp-2013-307349. PMID 24667206. 27. ^ Spetzler RF, Yashar K, Peter N. Neurovascular surgery. ISBN 9781604067590. OCLC 967842929. 28. ^ "Cavernous malformations". Neurovascular Surgery Brain Aneurysm & AVM Center. Massachusetts General Hospital. Archived from the original on 3 February 2014. 29. ^ "Benign Liver Tumors". American Liver Foundation. 2011. 30. ^ Poorthuis MH, Klijn CJ, Algra A, Rinkel GJ, Al-Shahi Salman R (December 2014). "Treatment of cerebral cavernous malformations: a systematic review and meta-regression analysis". Journal of Neurology, Neurosurgery, and Psychiatry. 85 (12): 1319–23. doi:10.1136/jnnp-2013-307349. PMID 24667206. 31. ^ Poorthuis M, Samarasekera N, Kontoh K, Stuart I, Cope B, Kitchen N, Al-Shahi Salman R (April 2013). "Comparative studies of the diagnosis and treatment of cerebral cavernous malformations in adults: systematic review". Acta Neurochirurgica. 155 (4): 643–9. doi:10.1007/s00701-013-1621-4. PMID 23371401. S2CID 7859921. 32. ^ Polster SP, Cao Y, Carroll T, Flemming K, Girard R, Hanley D, et al. (April 2019). "Trial Readiness in Cavernous Angiomas With Symptomatic Hemorrhage (CASH)". Neurosurgery. 84 (4): 954–964. doi:10.1093/neuros/nyy108. PMC 6500884. PMID 29660039. 33. ^ "Update Your Cavernous Angioma Patient Registry Profile". Angioma Alliance. Retrieved 2020-08-03. ## Further reading[edit] * Robinson JR, Awad IA, Little JR (November 1991). "Natural history of the cavernous angioma". Journal of Neurosurgery. 75 (5): 709–14. doi:10.3171/jns.1991.75.5.0709. PMID 1919692. * Del Curling O, Kelly DL, Elster AD, Craven TE (November 1991). "An analysis of the natural history of cavernous angiomas". Journal of Neurosurgery. 75 (5): 702–8. doi:10.3171/jns.1991.75.5.0702. PMID 1919691. S2CID 23832599. Classification D * ICD-10: D18.0 * MeSH: D006392 * v * t * e Tumours of blood vessels Blood vessel * Hemangiosarcoma * Blue rubber bleb nevus syndrome * Hemangioendothelioma * Composite * Endovascular papillary * Epithelioid * Kaposiform * Infantile * Retiform) * Spindle cell * Proliferating angioendotheliomatosis * Hemangiopericytoma * Venous lake * Kaposi's sarcoma * African cutaneous * African lymphadenopathic * AIDS-associated * Classic * Immunosuppression-associated * Hemangioblastoma * Hemangioma * Capillary * Cavernous * Glomeruloid * Microvenular * Targeted hemosiderotic * Angioma * Cherry * Seriginosum * Spider * Tufted * Universal angiomatosis * Angiokeratoma * of Mibelli * Angiolipoma * Pyogenic granuloma Lymphatic * Lymphangioma/lymphangiosarcoma * Lymphangioma circumscriptum * Acquired progressive lymphangioma * PEComa * Lymphangioleiomyomatosis * Cystic hygroma * Multifocal lymphangioendotheliomatosis * Lymphangiomatosis Either * Angioma/angiosarcoma * Angiofibroma [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Cavernous hemangioma	c0018920	25,032	wikipedia	https://en.wikipedia.org/wiki/Cavernous_hemangioma	2021-01-18T18:31:50	{"mesh": ["D006392"], "umls": ["C0018920"], "wikidata": ["Q1737261"]}
Fenichel et al. (1967) described a family in which weakness was confined mainly to the face and pectoral girdle musculature. Onset was in early adult life and the disorder was slowly progressive. The disorder superficially resembles facioscapulohumeral muscular dystrophy, from which it is differentiated by muscle histology and electromyography. Siddique et al. (1989) could prove no linkage with 10 expressed and 7 RFLP markers. Two areas of possible linkage were defined on chromosomes 1p and 4q with the markers MNS (maximum lod = 1.47 at theta = 0.10) and PGM1 (maximum lod = 0.94 at theta = 0.001), respectively. Muscle \- Face and pectoral girdle muscular atrophy Misc \- Onset in early adult life Inheritance \- Autosomal dominant form ▲ 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	SPINAL MUSCULAR ATROPHY, FACIOSCAPULOHUMERAL TYPE	c1866783	25,033	omim	https://www.omim.org/entry/182970	2019-09-22T16:34:44	{"mesh": ["C566674"], "omim": ["182970"], "synonyms": ["Alternative titles", "FSHSMA"]}
Craniorachischisis is the most severe form of neural tube defect in which both the brain and spinal cord remain open to varying degrees. It is a very rare congenital malformation of the central nervous system. ## Epidemiology The prevalence is not known. ## Clinical description Craniorachischisis totalis, the most complete form of craniorachischisis, presents anencephaly and total spina bifida together and is lethal. ## Etiology As with other neural tube defects, craniorachischisis is thought to be of multifactorial origin. ## Antenatal diagnosis Antenatal diagnosis is possible by ultrasonographic monitoring. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Craniorachischisis	c0152426	25,034	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=63260	2021-01-23T16:56:05	{"gard": ["10504"], "mesh": ["D009436"], "umls": ["C0152426"], "icd-10": ["Q00.1"]}
## Description Melorheostosis (MEL) is characterized by 'flowing' hyperostosis of the cortex of tubular bones. The lesions are usually asymmetric and involve only 1 limb or correspond to a particular sclerotome. They may be accompanied by abnormalities of adjacent soft tissue, including joint contractures, sclerodermatous skin lesions, muscle atrophy, or hemangiomas (review by Hellemans et al., 2004). The designation combines root words meaning 'limb,' 'flow,' and 'bone.' Melorheostosis may sometimes be a feature of Buschke-Ollendorff syndrome (BOS; 166700), a benign disorder which is caused by mutation in the LEMD3 gene (607844). Although germline or somatic LEMD3 mutations had been postulated to cause isolated melorheostosis (Butkus et al., 1997; Debeer et al., 2003; Happle, 2004; Hellemans et al., 2004), several studies have not been able to prove this (Hellemans et al., 2004; Mumm et al., 2007; Zhang et al., 2009). Clinical Features Fryns et al. (1980) reported a 3-year-old girl with clinical and radiologic findings of melorheostosis involving the left lower limb and associated with scleroderma of the overlying soft tissue. Subsequently, at age 17 years, she was admitted to hospital for an Ilizarov operation for lengthening and axis correction of the left tibia. Arterial hypertension (220/130 mm Hg) was noted, and biochemical studies documented high plasma renin activity and high aldosterone concentrations. Renal studies showed a small left kidney, and angiography showed several intrarenal high-grade stenoses of the left renal artery with poor opacification. Partial nephrectomy with removal of the upper and middle portions of the left kidney was performed. Pathologic examination of the small and large blood vessels showed marked intimal proliferation and splitting of the elastica. Roger et al. (1994) reported that vascular anomalies, such as capillary hemangiomata, lymphangiectasis, vascular nevi, glomus tumors, and arteriovenous aneurysms occur in at least 5% of reported patients. This and the fact that soft tissues overlying the skeletal changes show abnormalities suggested to Fryns (1995) that 'melorheostosis, like Proteus syndrome (176920), may be another example of an early postzygotic mutation of the mesenchyme resulting in asymmetric involvement of skeletal structures, with concomitant vascular and hamartomatous changes in the overlying soft tissues.' Mumm et al. (2007) reported 4 unrelated patients with sporadic melorheostosis. One girl was affected in the left hand, with lesions in the radial carpal bones and overlying tight skin. Another girl developed ulnar deviation of her right wrist and middle finger and her left thumb. She had significant flexion contractures of some fingers and her right elbow. An 8-year-old boy had congenital deformity of his left leg and foot caused by progressive MEL; skin atrophy affected the foot. Zhang et al. (2009) reported a 39-year-old man from the U.K. with sporadic melorheostosis. He had a painful flexion deformity of the right elbow. Radiographs showed extensive flowing endosteal hyperostosis that affected the humeral and radial shaft as well as the distal epiphyses with ectopic calcifications in the antecubital fossa. He had no relevant family history of a similar disorder. Molecular Genetics ### Exclusion Studies Mumm et al. (2007) did not identify germline mutations in the LEMD3 gene (607844) in any of 4 unrelated patients with sporadic isolated melorheostosis. Zhang et al. (2009) did not identify germline or somatic mutations in the LEMD3 gene in a U.K. man with sporadic melorheostosis. Both Mumm et al. (2007) and Zhang et al. (2009) concluded that mutation in the LEMD3 gene does not cause isolated melorheostosis. History Happle (1996) presented a concept of type 2 segmental disorders in conditions such as melorheostosis, which is nonhereditary and always shows a segmental arrangement. Type 1 segmental involvement reflects, it was suggested, heterozygosity resulting from a de novo mutation in an otherwise healthy embryo; a type 2 segmental manifestation may be best explained by loss of heterozygosity occurring in a heterozygous embryo at an early developmental stage. Happle (2004) suggested that melorheostosis originates from an early mutation event with loss of the corresponding wildtype allele at the gene locus of osteopoikilosis (166700). INHERITANCE \- Isolated cases SKELETAL \- Contractures over affected bones \- Flexion deformities over affected bones \- Melorheostosis \- Flowing hyperostosis of bone cortex \- Osteosclerosis (lesions mainly affect diaphyses of long bones, hands, feet, and pelvis although epiphyses may also be affected) SKIN, NAILS, & HAIR Skin \- Skin atrophy over affected bones \- Sclerotic soft tissue over affected bones MISCELLANEOUS \- Onset in childhood \- Progressive disorder \- Segmental distribution often affecting 1 limb ▲ 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	MELORHEOSTOSIS, ISOLATED	c0025239	25,035	omim	https://www.omim.org/entry/155950	2019-09-22T16:38:29	{"doid": ["4253"], "mesh": ["D008557"], "omim": ["155950"], "orphanet": ["2485"], "synonyms": ["Alternative titles", "MEL"]}
Isolated congenital asplenia Other namesICAS Isolated congenital asplenia is a rare disease in humans that can cause life-threatening bacterial infections in children due to primary immunodeficiency.[1][2][3][4] The infections can include pneumococal sepsis and meningitis.[2][5] ICAS is a ribosomopathy,[6] due to autosomal dominant mutation of the RPSA gene on chromosome 3p21.[4][7] Unlike heterotaxy syndrome,[8] the absent spleen (asplenia) is not associated with other structural developmental defects.[3][4] In some cases the spleen is present, but very small and nonfunctional (hyposplenism). [9] ## Immunodeficiency[edit] The spleen is an organ within the lymphatic system and its primary function is to filter blood. However, the spleen also plays a key role in immune responses as it detects pathogens within the blood and secretes phagocytes to fight potential infection. Without these immune functions, individuals with isolated congenital asplenia are extremely susceptible to infection. [10] Streptococcus pneumoniae is a common bacteria that affects individuals with ICAS, often causes meningitis, sepsis, and otitis media. [9] ## References[edit] 1. ^ Online Mendelian Inheritance in Man. OMIM entry 271400: Asplenia, isolated congenital; ICAS. Johns Hopkins University. [1] 2. ^ a b Ahmed SA, Zengeya S, Kini U, Pollard AJ (2010). "Familial isolated congenital asplenia: case report and literature review". Eur. J. Pediatr. 169 (3): 315–8. doi:10.1007/s00431-009-1030-0. PMID 19618213. S2CID 8132002.CS1 maint: uses authors parameter (link) 3. ^ a b Mahlaoui N, Minard-Colin V, Picard C, et al. (2011). "Isolated congenital asplenia: a French nationwide retrospective survey of 20 cases". J. Pediatr. 158 (1): 142–8, 148.e1. doi:10.1016/j.jpeds.2010.07.027. PMID 20846672. 4. ^ a b c Bolze A, Mahlaoui N, Byun M, et al. (2013). "Ribosomal protein SA haploinsufficiency in humans with isolated congenital asplenia". Science. 340 (6135): 976–8. Bibcode:2013Sci...340..976B. doi:10.1126/science.1234864. PMC 3677541. PMID 23579497. 5. ^ Shachor-Meyouhas Y, Sprecher H, Kassis I (2010). "Isolated congenital asplenia--a rare cause of severe pneumococcal sepsis". Harefuah (in Hebrew and English). 149 (8): 486–9, 552. PMID 21341424.CS1 maint: uses authors parameter (link) 6. ^ McCann KL, Baserga SJ (2013). "Genetics. Mysterious ribosomopathies". Science. 341 (6148): 849–50. doi:10.1126/science.1244156. PMC 3893057. PMID 23970686.CS1 maint: uses authors parameter (link) 7. ^ Online Mendelian Inheritance in Man. OMIM entry 150370: Ribosomal protein SA; RPSA. Johns Hopkins University. [2] 8. ^ Online Mendelian Inheritance in Man. OMIM entry 208530: Right atrial isomerism; RAI. Johns Hopkins University. [3] 9. ^ a b Reference, Genetics Home. "Isolated congenital asplenia". Genetics Home Reference. Retrieved 2020-09-18. 10. ^ "The spleen: Anatomy, function, and disease". www.medicalnewstoday.com. 2018-01-23. Retrieved 2020-09-18. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Isolated congenital asplenia	c0685889	25,036	wikipedia	https://en.wikipedia.org/wiki/Isolated_congenital_asplenia	2021-01-18T18:38:02	{"mesh": ["C563028"], "umls": ["C0685889", "C1849084"], "orphanet": ["101351"], "wikidata": ["Q25324166"]}
A rare, acute myeloid leukemia characterized by evidence of granulocytic maturation and more than 20% of blast cells in the bone marrow and/or peripheral blood. The maturing non-blast granulocytic cells account for greater than or equal to 10% and monocytic cells less than or equal to 20% of the bone marrow cells. Various degrees of anemia, thrombocytopenia, or pancytopenia are present. Frequent clinical manifestations include fatigue, fever, bleeding disorders, and organomegaly, especially hepatosplenomegaly. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Acute myeloblastic leukemia with maturation	c1879321	25,037	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98834	2021-01-23T18:36:54	{"gard": ["527"], "mesh": ["D015470"], "umls": ["C1879321"], "icd-10": ["C92.0"], "synonyms": ["AML M2", "Acute myeloblastic leukemia M2"]}
A number sign (#) is used with this entry because of evidence that autosomal dominant congenital stationary night blindness-3 (CSNBAD3) is caused by heterozygous mutation in the GNAT1 gene (139330) on chromosome 3p21. An autosomal recessive form of CSNB (CSNB1G; 616389) is also caused by mutation in the GNAT1 gene. For a general phenotypic description and discussion of genetic heterogeneity of congenital stationary night blindness, see CSNB1A (310500). Clinical Features Dryja et al. (1996) summarized early reports of the most famous family with dominantly inherited night blindness, that descended for some 11 generations from Jean Nougaret (1637-1719), a butcher from Provence who settled in Vendemian, a small village near Montpellier in the south of France. Florent Cunier, the Belgian ophthalmologist who founded Annales d'oculistique, heard of the family, examined some affected members, and stimulated M. Chauvet, a local antiquarian, to assemble the family genealogy. It was Chauvet who showed that Nougaret was the common ancestor of all persons in the district with night blindness. His genealogy listed 629 persons of whom 86 were night blind. Cunier (1838) published the findings. Nettleship (1907) followed up on the family. (An interesting biography of Nettleship was published in JAMA (Anonymous, 1970)). By that time, 135 night-blind persons were known. Vision was unimpaired in daylight, the fundi were normal, and general health was excellent. The excess of normal over affected observed in this family among offspring of affected persons may be a matter of incomplete penetrance or incomplete recording of mild cases--a view subscribed to by the geneticist William Bateson who discussed the paper. Attempts at further follow-up by Dejean and Gassenc (1949) indicated that the village inhabited by Nougaret's descendants was no longer an isolate. Dryja et al. (1996) noted that patients with the Nougaret type of night blindness have no rod a-wave, suggesting a defect inherent in the rod photoreceptors themselves. Szabo et al. (2007) reported a 3-generation Danish family in which 9 members exhibited typical symptoms of congenital stationary night blindness, with nonprogressive night blindness from early infancy. Four patients who underwent detailed clinical investigation had normal visual acuity and color vision, no constriction of visual fields, and unremarkable fundus examination. Dark adaptometry confirmed complete night blindness in 3 of the patients, whereas the youngest patient exhibited a Riggs-type electroretinographic (ERG) pattern that suggested a presynaptic defect in rod phototransduction. Reexamination of 2 of the 4 patients 20 years later, at the ages of 51 and 57 years, confirmed the nonprogressive nature of the condition. Another family member had constricted visual fields, peripheral hyperpigmentation of the retina, and an extinguished ERG, which are typical symptoms of a degenerative retinopathy such as retinitis pigmentosa (RP; see 268000). Mapping In 16 members of a 3-generation Danish family segregating autosomal dominant CSNB, Szabo et al. (2007) performed microsatellite mapping of 3 known CSNBAD loci. Two-point linkage analysis yielded negative scores at 2 of the loci; however, D3S1289, located close to the GNAT1 gene, gave positive lod scores of 1.81 (theta = 0). Molecular Genetics Dryja et al. (1996) reported that affected descendants of Jean Nougaret with congenital night blindness carry a missense mutation in the gene encoding the alpha subunit of rod transducin (GNAT1), the G protein that couples rhodopsin to cGMP-phosphodiesterase in the phototransduction cascade. They analyzed 2 affected sibs for 11 genes in the phototransduction cascade and in both they detected an abnormality in exon 2 of the alpha subunit of rod transducin by SSCP analysis. Sequencing revealed a point mutation in codon 38 (139330.0001) resulting in a G38D amino acid change. No other changes in the coding region or flanking intron sequences were found by SSCP. Dryja et al. (1996) reported that subsequent analysis of 27 relatives revealed that the mutation was present only in affected family members. Dryja et al. (1996) noted that gly38 is a highly conserved residue among heteromeric G proteins including p21(RAS) (see 190020). In a 3-generation Danish family with autosomal dominant CSNB mapping to chromosome 3p, Szabo et al. (2007) identified a heterozygous missense mutation in the GNAT1 gene (Q200E; 139330.0002), which segregated with the disease and was not found in 104 control alleles. One affected family member who exhibited typical symptoms of RP was heterozygous for the mutation; his daughter, who inherited the mutation, had typical signs of CSNB but no symptoms of RP at age 57 years. Szabo et al. (2007) concluded that the simultaneous occurrence of CSNB and RP in the father was coincidental. INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Nonprogressive night blindness from infancy or early childhood \- Normal visual acuity \- Unremarkable funduscopic examination \- Markedly decreased or absent scotopic responses on electroretinography (ERG) \- Normal or slightly reduced photopic responses on ERG MOLECULAR BASIS \- Caused by mutation in the guanine nucleotide-binding protein, alpha-transducing activity polypeptide-1 gene (GNAT1, 139330.0001 ) ▲ 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	NIGHT BLINDNESS, CONGENITAL STATIONARY, AUTOSOMAL DOMINANT 3	c0339535	25,038	omim	https://www.omim.org/entry/610444	2019-09-22T16:04:30	{"doid": ["0110715"], "mesh": ["C536122"], "omim": ["610444"], "orphanet": ["215"], "synonyms": ["Alternative titles", "NIGHT BLINDNESS, CONGENITAL STATIONARY, NOUGARET TYPE"]}
Pilomatricoma, also known as pilomatrixoma, is a type of noncancerous (benign) skin tumor associated with hair follicles. Hair follicles are specialized structures in the skin where hair growth occurs. Pilomatricomas occur most often on the head or neck, although they can also be found on the arms, torso, or legs. A pilomatricoma feels like a small, hard lump under the skin. This type of tumor grows relatively slowly and usually does not cause pain or other symptoms. Most affected individuals have a single tumor, although rarely multiple pilomatricomas can occur. If a pilomatricoma is removed surgically, it tends not to grow back (recur). Most pilomatricomas occur in people under the age of 20. However, these tumors can also appear later in life. Almost all pilomatricomas are benign, but a very small percentage are cancerous (malignant). Unlike the benign form, the malignant version of this tumor (known as a pilomatrix carcinoma) occurs most often in middle age or late in life. Pilomatricoma usually occurs without other signs or symptoms (isolated), but this type of tumor has also rarely been reported with inherited conditions. Disorders that can be associated with pilomatricoma include Gardner syndrome, which is characterized by multiple growths (polyps) and cancers of the colon and rectum; myotonic dystrophy, which is a form of muscular dystrophy; and Rubinstein-Taybi syndrome, which is a condition that affects many parts of the body and is associated with an increased risk of both benign and malignant tumors. ## Frequency Pilomatricoma is an uncommon tumor. The exact prevalence is unknown, but pilomatricoma probably accounts for less than 1 percent of all benign skin tumors. ## Causes Mutations in the CTNNB1 gene are found in almost all cases of isolated pilomatricoma. These mutations are somatic, which means they are acquired during a person's lifetime and are present only in tumor cells. Somatic mutations are not inherited. The CTNNB1 gene provides instructions for making a protein called beta-catenin. This protein plays an important role in sticking cells together (cell adhesion) and in communication between cells. It is also involved in cell signaling as part of the Wnt signaling pathway. This pathway promotes the growth and division (proliferation) of cells and helps determine the specialized functions a cell will have (differentiation). Wnt signaling is involved in many aspects of development before birth, as well as the maintenance and repair of adult tissues. Among its many activities, beta-catenin appears to be necessary for the normal function of hair follicles. This protein is active in cells that make up a part of the hair follicle known as the matrix. These cells divide and mature to form the different components of the hair follicle and the hair shaft. As matrix cells divide, the hair shaft is pushed upward and extends beyond the skin. Mutations in the CTNNB1 gene lead to a version of beta-catenin that is always turned on (constitutively active). The overactive protein triggers matrix cells to divide too quickly and in an uncontrolled way, leading to the formation of a pilomatricoma. Most pilomatrix carcinomas, the malignant version of pilomatricoma, also have somatic mutations in the CTNNB1 gene. It is unclear why some pilomatricomas are cancerous but most others are not. ### Learn more about the gene associated with Pilomatricoma * CTNNB1 ## Inheritance Pattern Most people with isolated pilomatricoma do not have any other affected family members. However, rare families with multiple affected members have been reported. In these cases, the inheritance pattern of the condition (if any) is unknown. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Pilomatricoma	c0206711	25,039	medlineplus	https://medlineplus.gov/genetics/condition/pilomatricoma/	2021-01-27T08:25:42	{"gard": ["9452"], "mesh": ["D018296"], "omim": ["132600"], "synonyms": []}
Colorectal adenoma Tubulovillous adenoma (tubular component – left of image, villous component – right of image). H&E stain. SpecialtyGastroenterology SymptomsAsymptomatic, rectal bleeding ComplicationsColorectal cancer Diagnostic methodColonoscopy TreatmentPolypectomy The colorectal adenoma is a benign glandular tumor of the colon and the rectum. It is a precursor lesion of the colorectal adenocarcinoma (colon cancer).[1][2][3] They often manifest as colorectal polyps. ## Contents * 1 Comparison table * 2 Tubular adenoma * 3 Tubulovillous adenoma * 4 Villous adenoma * 5 Sessile serrated adenoma * 6 See also * 7 References ## Comparison table[edit] Incidences and malignancy risks of various types of colorectal polyps. Adenomatous types are grouped at top. Colorectal adenoma Type Risk of containing malignant cells Histopathology definition Tubular adenoma 2% at 1.5cm[4] Over 75% of volume has tubular appearance.[5] Tubulovillous adenoma 20% to 25%[6] 25–75% villous[5] Villous adenoma 15%[7] to 40%[6] Over 75% villous[5] Sessile serrated adenoma (SSA)[8] * Basal dilation of the crypts * Basal crypt serration * Crypts that run horizontal to the basement membrane (horizontal crypts) * Crypt branching. ## Tubular adenoma[edit] Normal (left) versus dysplastic (large at right) colonic crypts, the latter conferring a diagnosis of a tubular adenoma. In constrast to hyperplastic polyps, these display dysplasia.[citation needed] ## Tubulovillous adenoma[edit] Tubulovillous adenoma, TVA are considered to have a higher risk of becoming malignant (cancerous) than tubular adenomas.[9] ## Villous adenoma[edit] These adenomas may become malignant (cancerous). Villous adenomas have been demonstrated to contain malignant portions in about 15–25% of cases, approaching 40% in those over 4 cm in diameter.[7] Colonic resection may be required for large lesions. These can also lead to secretory diarrhea with large volume liquid stools with few formed elements. They are commonly described as secreting large amounts of mucus, resulting in hypokalaemia in patients. On endoscopy, a "cauliflower' like mass is described due to villi stretching. Being an adenoma, the mass is covered in columnar epithelial cells.[citation needed] * Micrograph of a colorectal villous adenoma. H&E stain ## Sessile serrated adenoma[edit] Main article: Sessile serrated adenoma Micrograph of a sessile serrated adenoma. H&E stain Sessile serrated adenomas are characterized by (1) basal dilation of the crypts, (2) basal crypt serration, (3) crypts that run horizontal to the basement membrane (horizontal crypts), and (4) crypt branching. The most common of these features is basal dilation of the crypts. ## See also[edit] * Colorectal cancer * Colorectal polyp ## References[edit] 1. ^ Hardcastle, J. D.; Armitage, N. C. (1984). "Early diagnosis of colorectal cancer: A review". Journal of the Royal Society of Medicine. 77 (8): 673–6. PMC 1440108. PMID 6384511. 2. ^ Schofield, P. F.; Jones, D. J. (1992). "ABC of colorectal diseases. Colorectal neoplasia—I: Benign colonic tumours". BMJ (Clinical research ed.). 304 (6840): 1498–500. doi:10.1136/bmj.304.6840.1498. PMC 1882234. PMID 1319254. 3. ^ Srivastava, S; Verma, M; Henson, D. E. (2001). "Biomarkers for early detection of colon cancer". Clinical Cancer Research. 7 (5): 1118–26. PMID 11350874. 4. ^ Minhhuyen Nguyen. "Polyps of the Colon and Rectum". MSD Manual. Last full review/revision June 2019 5. ^ a b c Bosman, F. T. (2010). WHO classification of tumours of the digestive system. Lyon: International Agency for Research on Cancer. ISBN 92-832-2432-9. OCLC 688585784. 6. ^ a b Amersi, Farin; Agustin, Michelle; Ko, Clifford Y (2005). "Colorectal Cancer: Epidemiology, Risk Factors, and Health Services". Clinics in Colon and Rectal Surgery. 18 (03): 133–140. doi:10.1055/s-2005-916274. ISSN 1531-0043. PMC 2780097. 7. ^ a b Alnoor Ramji. "Villous Adenoma Follow-up". Medscape. Updated: Oct 24, 2016 8. ^ Rosty, C; Hewett, D. G.; Brown, I. S.; Leggett, B. A.; Whitehall, V. L. (2013). "Serrated polyps of the large intestine: Current understanding of diagnosis, pathogenesis, and clinical management". Journal of Gastroenterology. 48 (3): 287–302. doi:10.1007/s00535-012-0720-y. PMC 3698429. PMID 23208018. 9. ^ Levine JS, Ahnen DJ (December 2006). "Clinical practice. Adenomatous polyps of the colon". N. Engl. J. Med. 355 (24): 2551–7. doi:10.1056/NEJMcp063038. PMID 17167138. * v * t * e Digestive system neoplasia GI tract Upper Esophagus * Squamous cell carcinoma * Adenocarcinoma Stomach * Gastric carcinoma * Signet ring cell carcinoma * Gastric lymphoma * MALT lymphoma * Linitis plastica Lower Small intestine * Duodenal cancer * Adenocarcinoma Appendix * Carcinoid * Pseudomyxoma peritonei Colon/rectum * Colorectal polyp: adenoma, hyperplastic, juvenile, sessile serrated adenoma, traditional serrated adenoma, Peutz–Jeghers Cronkhite–Canada * Polyposis syndromes: Juvenile * MUTYH-associated * Familial adenomatous/Gardner's * Polymerase proofreading-associated * Serrated polyposis * Neoplasm: Adenocarcinoma * Familial adenomatous polyposis * Hereditary nonpolyposis colorectal cancer Anus * Squamous cell carcinoma Upper and/or lower * Gastrointestinal stromal tumor * Krukenberg tumor (metastatic) Accessory Liver * malignant: Hepatocellular carcinoma * Fibrolamellar * Hepatoblastoma * benign: Hepatocellular adenoma * Cavernous hemangioma * hyperplasia: Focal nodular hyperplasia * Nodular regenerative hyperplasia Biliary tract * bile duct: Cholangiocarcinoma * Klatskin tumor * gallbladder: Gallbladder cancer Pancreas * exocrine pancreas: Adenocarcinoma * Pancreatic ductal carcinoma * cystic neoplasms: Serous microcystic adenoma * Intraductal papillary mucinous neoplasm * Mucinous cystic neoplasm * Solid pseudopapillary neoplasm * Pancreatoblastoma Peritoneum * Primary peritoneal carcinoma * Peritoneal mesothelioma * Desmoplastic small round cell tumor [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Colorectal adenoma	c0206677	25,040	wikipedia	https://en.wikipedia.org/wiki/Colorectal_adenoma	2021-01-18T18:43:09	{"mesh": ["D018256"], "umls": ["C0206677"], "wikidata": ["Q2825480"]}
Immunotactoid or fibrillary glomerulopathy is a group of very rare glomerular diseases, composed of immunotactoid glomerulopathy (ITG) and non-amyloid fibrillary glomerulopathy (non-amyloid FGP) (see these terms), that are characterized by mesangial deposition of monoclonal microtubular or polyclonal fibrillar deposits. Both present clinically with nephrotic range proteinuria, hematuria and renal insufficiency leading to renal failure in many cases. ITG is more likely to manifest with underlying lymphoproliferative disease, hypocomplementemia, dysproteinemia, monoclonal gammopathy or occult cryoglobulinemia. Non-amyloid FGP is 10 times more frequent than ITG. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Immunotactoid or fibrillary glomerulopathy	None	25,041	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=91137	2021-01-23T17:58:51	{"gard": ["12741"], "icd-10": ["N03.6"], "synonyms": ["Immunotactoid or fibrillary glomerulonephritis"]}
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 2012) Biliary fever is an illness of the liver affecting horses,[1] dogs[2] and cats.[3] This is currently the most common infectious disease of dogs in Southern Africa. It is also known as tick bite fever or "Bosluiskoors" in Afrikaans. It is caused by a tiny parasite (Babesia canis) which is introduced into the body by a tick bite. This parasite then enters and destroys red blood cells. Biliary in dogs has a lot in common with malaria in man, except that in the latter, a mosquito is the vector. ## Contents * 1 Presentation * 2 Diagnosis * 3 Prevention * 4 Treatment * 4.1 Diet * 5 References ## Presentation[edit] The peracute (very sudden and severe) form causes death within a few hours and treatment is of little avail. More commonly dogs suffer from the acute or subacute form. This is recognised by the dog being listless or lethargic, losing its appetite and running a temperature. If your dog is off its food, take a rectal temperature reading. If this is 39 °C or higher you should have the dog examined – do not wait until its mucous membranes become pale, white or yellow, which commonly suggests a more advanced stage of the disease. Fever is present only while the patient is actively fighting the parasite; the disease may be present with a normal (38,5 °C) or subnormal temperature. Yellow faeces and brown or red urine also suggests the presence of biliary fever. ## Diagnosis[edit] A small drop of blood is collected and a smear made. Once stained, the parasites can be seen in the red blood cells under microscopic evaluation.[4] ## Prevention[edit] A vaccine has been launched in South Africa at the end of 2008. Nobivac Piro, has been proven effective when combined with twice yearly booster shots. Rely on reducing the dog's tick population by regular use of approved tick control measures that may be recommended by a veterinarian. ## Treatment[edit] Treatment should only be given after a positive diagnosis has been made by means of a blood test. Usually treatment is effective, depending on several factors, but the majority will respond. In early cases simple injections are usually sufficient, but in others blood transfusions, electrolyte infusions per vein, liver tonics, blood-building, etc., may be required. ### Diet[edit] Avoid fatty foods, and give a good quality balanced dog food. A tonic and/or follow up treatment may be required if the animal does not appear to be responding to the initial treatment. ## References[edit] 1. ^ Boden, Edward; Geoffrey Philip West (1998). Black's Veterinary Dictionary. Rowman & Littlefield. p. 167. ISBN 978-0-389-21017-7. 2. ^ Griffiths, Henry Joseph (1978). A Handbook of Veterinary Parasitology. University of Minnesota Press. p. 5. ISBN 978-0-8166-0834-8. 3. ^ Jackson, C.; F.J. Dunning (1937). "Biliary fever (nuttalliosis) of the cat. a case in the Stellenbosch District". Journal of the South African Veterinary Medical Association. 8: 83–88. 4. ^ http://www.vetcareclinics.co.za/educare/an-overview-of-biliary-in-dogs/4 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Biliary fever	None	25,042	wikipedia	https://en.wikipedia.org/wiki/Biliary_fever	2021-01-18T19:01:09	{"wikidata": ["Q4907740"]}
Protothecosis Histologic stain of a Prototheca zopfii infection in a dog SpecialtyInfectious disease Protothecosis is a disease found in dogs, cats, cattle, and humans caused by a type of green alga known as Prototheca that lacks chlorophyll. It and its close relative Helicosporidium are unusual in that they are actually green algae that have become parasites.[1] The two most common species are Prototheca wickerhamii and Prototheca zopfii. Both are known to cause disease in dogs, while most human cases are caused by P. wickerhami.[2] Prototheca is found worldwide in sewage and soil. Infection is rare despite high exposure, and can be related to a defective immune system.[3] In dogs, females and Collies are most commonly affected.[4] The first human case was identified in 1964 in Sierra Leone.[5] ## Contents * 1 Cause * 2 Treatment * 3 In cattle * 4 In dogs * 5 See also * 6 References * 7 External links ## Cause[edit] Photomicrograph of Prototheca wickerhamii infection in a human. Note the floret-like arrangements. Hematoxylin and eosin stain. Photomicrograph of Prototheca wickerhamii infection in a human. Note the floret-like arrangements. Gomori methenamine silver(GMS) stain. Photomicrograph of Prototheca wickerhamii infection in a human. Note the floret-like arrangements. Periodic acid-Schiff(PAS) stain. Prototheca has been thought to be a mutant of Chlorella, a type of single-celled green alga. However, while Chlorella contains galactose and galactosamine in the cell wall, Prototheca lacks these. Also, Chlorella obtains its energy through photosynthesis, while Prototheca is saprotrophic, feeding on dead and decaying organic matter. When Prototheca was first isolated from slime flux of trees in 1894, it was thought to be a type of fungus.[6] Its size varies from 2 to 15 micrometres.[7] ## Treatment[edit] Treatment with amphotericin B has been reported.[8] ## In cattle[edit] Cattle can be affected by protothecal enteritis and mastitis.[9] Protothecal mastitis is endemic worldwide, although most cases of infected herds have been reported in Germany, the United States, and Brazil.[10] ## In dogs[edit] Disseminated protothecosis is most commonly seen in dogs. The algae enters the body through the mouth or nose and causes infection in the intestines. From there it can spread to the eye, brain, and kidneys. Symptoms can include diarrhea, weight loss, weakness, inflammation of the eye (uveitis), retinal detachment, ataxia, and seizures.[11] Dogs with acute blindness and diarrhea that develop exudative retinal detachment should be assessed for protothecosis.[6] Diagnosis is through culture or finding the organism in a biopsy, cerebrospinal fluid, vitreous humour, or urine. Treatment of the disseminated form in dogs is very difficult, although use of antifungal medication has been successful in a few cases.[4] Prognosis for cutaneous protothecosis is guarded and depends on the surgical options. Prognosis for the disseminated form is grave. This may be due to delayed recognition and treatment.[3] ## See also[edit] * Progressive disseminated histoplasmosis * List of cutaneous conditions ## References[edit] 1. ^ Tartar A, Boucias DG, Adams BJ, Becnel JJ (2002). "Phylogenetic analysis identifies the invertebrate pathogen Helicosporidium sp as a green alga (Chlorophyta)". Int J Syst Evol Microbiol. 52 (Pt 1): 273–9. doi:10.1099/00207713-52-1-273. PMID 11837312. 2. ^ Leimann B, Monteiro P, Lazéra M, Candanoza E, Wanke B (2004). "Protothecosis". Med Mycol. 42 (2): 95–106. doi:10.1080/13695780310001653653. PMID 15124862. 3. ^ a b Hosaka S, Hosaka M (2004). "A case report of canine protothecosis". J Vet Med Sci. 66 (5): 593–7. doi:10.1292/jvms.66.593. PMID 15187378. 4. ^ a b Ettinger, Stephen J.; Feldman, Edward C. (1995). Textbook of Veterinary Internal Medicine (4th ed.). W.B. Saunders Company. ISBN 978-0-7216-6795-9. 5. ^ Lass-Flörl C, Fille M, Gunsilius E, Gastl G, Nachbaur D (2004). "Disseminated infection with Prototheca zopfii after unrelated stem cell transplantation for leukemia". J. Clin. Microbiol. 42 (10): 4907–8. doi:10.1128/JCM.42.10.4907-4908.2004. PMC 522359. PMID 15472379. 6. ^ a b Hollingsworth S (2000). "Canine protothecosis". Vet Clin North Am Small Anim Pract. 30 (5): 1091–101. doi:10.1016/S0195-5616(00)05008-7. PMID 11033876. 7. ^ Lee W, Lagios M, Leonards R (1975). "Wound infection by Prototheca wickerhamii, a saprophytic alga pathogenic for man". J Clin Microbiol. 2 (1): 62–6. PMC 274126. PMID 1225929. 8. ^ Mohabeer, A. J.; Kaplan, P. J.; Southern Jr, P. M.; Gander, R. M. (1997). "Algaemia due to Prototheca wickerhamii in a patient with myasthenia gravis". Journal of Clinical Microbiology. 35 (12): 3305–3307. PMC 230169. PMID 9399541. 9. ^ Osterstock J, Mansell J, Roussel A (2005). "Protothecal enteritis as a cause of protein-losing enteropathy in a bull". J Am Vet Med Assoc. 227 (9): 1476–9, 1418. doi:10.2460/javma.2005.227.1476. PMID 16279394. 10. ^ Roesler U, Hensel A (2003). "Longitudinal analysis of Prototheca zopfii-specific immune responses: correlation with disease progression and carriage in dairy cows". J Clin Microbiol. 41 (3): 1181–6. doi:10.1128/JCM.41.3.1181-1186.2003. PMC 150299. PMID 12624049. 11. ^ Gionfriddo, Juliet R. (March 2007). "An unusual cause of blindness in a Siberian husky". Veterinary Medicine. 102 (3): 172–178. ## External links[edit] Classification D * ICD-10: B88.8 (ILDS B88.83) * DiseasesDB: 33989 * SNOMED CT: 240915002 External resources * eMedicine: derm/348 * v * t * e Protozoan infection: SAR and Archaeplastida SAR Alveolate Apicomplexa Conoidasida/ Coccidia * Coccidia: Cryptosporidium hominis/Cryptosporidium parvum * Cryptosporidiosis * Cystoisospora belli * Isosporiasis * Cyclospora cayetanensis * Cyclosporiasis * Toxoplasma gondii * Toxoplasmosis Aconoidasida * Plasmodium falciparum/vivax/ovale/malariae/knowlesi * Malaria * Blackwater fever * Babesia * Babesiosis Ciliophora * Balantidium coli * Balantidiasis Heterokont * Blastocystis * Blastocystosis * Pythium insidiosum * Pythiosis Archaeplastida * Algaemia: Prototheca wickerhamii * Protothecosis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Protothecosis	c0033735	25,043	wikipedia	https://en.wikipedia.org/wiki/Protothecosis	2021-01-18T18:49:28	{"icd-10": ["B88.8"], "wikidata": ["Q1130632"]}
A rare syndromic frontonasal dysplasia characterized by distinctive facial dysmorphic features including hypertelorism, almond-shaped palpebral fissures, nasal deformity with creased ridge, depressed or absent tip, and asymmetry and partial absence of nasal bones, and downturned corners of the mouth. Additional reported manifestations are limb anomalies (e. g. Poland anomaly, transverse limb agenesis, and anomalies of the hands and feet, such as camptodactyly, oligodactyly, clinodactyly, and syndactyly), frontonasal encephalocele, choanal atresia, congenital renal/cardiac malformations, and corpus callosum agenesis. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Frontonasal dysplasia-bifid nose-upper limb anomalies syndrome	None	25,044	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=521308	2021-01-23T18:00:43	{}
A number sign (#) is used with this entry because thyroid dyshormonogenesis-3 (TDH3) is caused by homozygous or compound heterozygous mutation in the thyroglobulin gene (TG; 188450) on chromosome 8q24. For a general phenotypic description and a discussion of genetic heterogeneity of thyroid dyshormonogenesis, see TDH1 (274400). Description Kanou et al. (2007) reviewed characteristics of thyroid dyshormonogenesis caused by mutations in the thyroglobulin (TG) gene. This form of thyroid dyshormonogenesis has an estimated prevalence of one in 100,000 newborns. Inherited in an autosomal recessive manner, the disorder in the majority of patients causes large goiters of elastic and soft consistency. Although the degree of thyroid dysfunction varies considerably among patients with defective TG synthesis, patients usually have a relatively high serum free T3 concentration with disproportionately low free T4 level. The maintenance of relatively high FT3 levels prevents profound tissue hypothyroidism except in brain and pituitary, which are dependent on T4 supply, resulting in neurologic and intellectual defects in some cases. Clinical Features Riddick et al. (1969) reported 3 goitrous members of a sibship of 4. These patients had hypothyroidism or compensated hypothyroidism, and had normal or high uptake of radioiodine; biochemical measurements on removed thyroid tissue showed absence of thyroglobulin with the appearance of abnormal light iodoproteins. Lissitzky et al. (1975) found a marked reduction of the carbohydrate moieties, supposedly necessary for secretion, in the thyroglobulin from a congenital goiter. Electron micrographs showed scarcity of colloid in the follicular lumen and overdistended, protein-filled endoplasmic reticulum. Cooper et al. (1981) reported a large kindred of patients with congenital goiter, followed for 15 years, in which a brother and sister developed metastatic follicular thyroid carcinoma (see 188550). Neither patient had evidence of the classic defects of T4 biosynthesis, but both had extremely rapid rates of iodine turnover. Based on their study of these patients and a review of published reports, Cooper et al. (1981) stated that development of metastatic thyroid cancer in patients with congenital goiter, occurring years after subtotal thyroidectomy without thyroid hormone replacement therapy, suggested a role for TSH in the genesis of thyroid cancer. De Vijlder et al. (1983) described a presumably autosomal dominant form of hereditary congenital goiter in a mother and 4 of her 8 children. Goiter was present in other members of the mother's family. Thyroglobulin was found to be reduced in the thyroid (17 mg/g thyroid tissue; normal value = 50) and was more negatively charged than normal, as shown by isoelectric focusing and DEAE-cellulose chromatography. Yoshida et al. (1996) identified a variant type of adenomatous goiter in 24 of 2,160 patients with adenomatous goiter who underwent thyroidectomy. The characteristics of the thyroid gland in these 24 patients included large goiter, small follicles, scant colloid, and columnar follicular cells containing yellow-green granules on hematoxylin-eosin staining. The thyroid gland was slightly orange-red, and electron microscopic examination showed abundant lysosomes with colloid droplets. When the features of this group were compared with those of 24 patients with common adenomatous goiter, the incidence of familial predisposition to thyroid disease in the former group was higher. The age at the time of detection of goiter was lower, i.e., 17 years in the variant type as opposed to 44 in the common type. Serum total T4 concentrations were lower in the variant group and serum TSH concentrations were higher in the variant group. Thyroid radioiodine uptake was remarkably increased, and lower levels of serum thyroglobulin were noted. The thyroglobulin content was low in the thyroid gland studied. The data suggested to Yoshida et al. (1996) that the etiology of this variant type of goiter is a hereditary abnormality in thyroglobulin synthesis. Hishinuma et al. (2005) reported a high incidence of thyroid cancer in long-standing goiters with thyroglobulin mutations. The authors reviewed 14 adult Japanese patients from 9 unrelated families, born before the initiation of neonatal thyroid screening in Japan, who had undergone multiple operations for very large goiters that first appeared in childhood. Of 11 patients who had undergone surgery, 7 had thyroid cancers; histologic examination revealed that 4 were multifocal papillary, 2 were unifocal papillary, and 1 was multifocal follicular. Analysis of exon 15 of the BRAF gene (164757) in 5 patients for whom thyroid tissue was available revealed 2 different heterozygous activating BRAF mutations (164757.0001 and 164757.0005) in 2 patients, respectively. Alzahrani et al. (2006) reported 2 brothers, born of consanguineous parents, who developed recurrent large goiters beginning at 1.5 years of age, requiring multiple partial thyroidectomies. At 15 years of age, the older brother underwent partial bilateral thyroidectomy and was diagnosed with thyroid cancer. Several years later, he presented with pain in the right femur; fine-needle aspiration of a subtrochanteric lesion revealed metastatic follicular thyroid carcinoma. He underwent completion thyroidectomy, for which histopathologic examination showed only hyperplastic nodules consistent with dyshormonogenesis, followed by apparently successful chemotherapy, with a negative iodine-123 whole-body and bone scans 3 years later. Diagnostic iodine-123 whole-body scans in his brother showed only residual tissue in the thyroid bed without evidence of distant activity; fine-needle aspiration of thyroid tissue showed no malignancy. The parents were unaffected, and there was a third unaffected brother. Inheritance Vono-Toniolo et al. (2005) stated that in most instances of TG-related goitrous hypothyroidism affected individuals have related parents and are homozygous for inactivating mutations in the TG gene. More rarely, compound heterozygous mutations lead to a loss of function of both alleles. Pathogenesis Vono-Toniolo et al. (2005) noted that molecular analyses had shown that at least some TG mutations result in a secretory defect and an endoplasmic reticulum storage disease. Diagnosis Increased metabolic activity of the gland or any block in thyroglobulin synthesis results in iodination of the serum albumin that diffuses into the hyperplastic thyroid (Stanbury, 1978). Patients previously classified as having familial plasma iodoprotein defects can be categorized as having some type of thyroglobulin abnormality or a familial abnormality of the thyroid such as Hashimoto struma (140300) or Graves disease (275000). ### Prenatal Diagnosis Medeiros-Neto et al. (1997) reported diagnosis of fetal dyshormonogenetic goiter with hypothyroidism, probably due to defective thyroglobulin synthesis, by ultrasound and cordocentesis at 28 weeks of gestation. They found that after a single injection of levothyroxine the fetal goiter decreased in size, and at birth the neonate had normal thyroid function. They concluded that congenital goitrous hypothyroidism can be diagnosed and treated prenatally with intraamniotic injection of thyroxine. Mapping In 5 affected and 5 unaffected members of a family with goiter due to a qualitative and quantitative defect in TG, Baas et al. (1984) analyzed the presence of an RFLP in the TG gene (188450) and found mendelian segregation of the polymorphism and goiter, suggesting that the rare variant was linked to a normal TG allele providing strong evidence for autosomal dominant inheritance of the TG synthesis defect in this family. Molecular Genetics Ieiri et al. (1991) gave the first report of individuals with documented TG gene mutations. The index patient and 2 of her 5 sibs presented with hypothyroidism, congenital goiter, and a marked impairment of TG synthesis. Analysis of a restriction fragment length polymorphism (RFLP) in the TG gene demonstrated that the affected individuals were homozygous for this allele and TG mRNA obtained from the goitrous tissue was slightly reduced in size compared to that from normal individuals. Sequencing of the cDNA revealed that exon 4 was missing from the major TG transcript in the goiter, and analysis of genomic DNA revealed a C-to-G transversion in the acceptor splice site of intron 3 (IVS3-3C-G; 188450.0001). Targovnik et al. (1989) provided the original description of a Brazilian family in which 3 mutations in 2 compound heterozygous combinations were found to segregate with the disorder (Gutnisky et al., 2004) (see 188450.0013). In 2 sibs with adenomatous goiter, Hishinuma et al. (2006) identified homozygosity for a mutation in the TG gene (188450.0006). Kitanaka et al. (2006) reported a Japanese girl with congenital goitrous hypothyroidism who was compound heterozygous for 2 mutations in the TG gene (188450.0017-188450.0018). She was identified with increased TSH in a neonatal screening test. Although serum T4 was low and serum TG undetectable, serum T3 was increased. Kanou et al. (2007) measured iodothyronine deiodinase type II (DIO2; 601413) in the thyroid gland of several patients with goiter who had mutations in the TG gene that cause a defect in the intracellular transport of TG (e.g., 188450.0005 and 188450.0015). They found a positive correlation between DIO2 activity and free T3/T4 ratios. In 2 brothers with recurrent large goiters, 1 of whom developed metastatic follicular thyroid carcinoma (see 188550), Alzahrani et al. (2006) analyzed the TG gene and identified homozygosity for a splice site mutation (188450.0018). The unaffected consanguineous parents were heterozygous for the mutation, which was not found in an unaffected brother. Alzahrani et al. (2006) also screened for RAS oncogene mutations by direct sequencing of thyroid tumor DNA, but identified no mutation in codons 12, 13, and 61 of the HRAS (190020), KRAS (190070), and NRAS (164790) oncogenes. The authors concluded that the malignant transformation of the congenital goiter was likely the result of prolonged TSH stimulation, probably in combination with mutations of oncogenes and/or tumor suppressor genes other than RAS. History Reports of patients with goitrous hypothyroidism caused by thyroglobulin defects have varied, with few patients having severe hypothyroidism. Some have a low protein-bound iodine level (PBI) commensurate with their low serum T4; others have a normal or elevated PBI with a low or low-normal serum T4. The thyroid may contain very small amounts of normally iodinated thyroglobulin or ample amounts of immunologically identifiable thyroglobulin with abnormal physical properties such as solubility (Michel et al., 1964), protease digestibility (McGirr et al., 1960), and iodinatibility (Kusakabe, 1972). In a review of inherited disorders of thyroid metabolism, Lever et al. (1983) discussed the heterogeneous group of disorders of hormonogenesis related to abnormal TG formation or secretion. Hypothyroidism in the goat and sheep has been related to a defect in mRNA for TG (Van Voorthuizen et al., 1978; Falconer et al., 1970). In 90 unrelated persons, Baas et al. (1984) screened the TG gene for RFLP; 1,164 nucleotides were screened using 15 different restriction enzymes. The average number of nucleotides screened per individual was 354. Only 1 polymorphism was found in these 1,164 nucleotides, with a minor allele frequency of 2.2%. The polymorphism was located in an intervening sequence. In the family with hereditary congenital hypothyroidism due to a defect in the synthesis and structure of thyroglobulin (de Vijlder et al., 1983), cosegregation of the rare defect and the polymorphism indicated that the hypothyroidism was caused by a mutation in the structural gene for thyroglobulin. Baas et al. (1984) suggested that since the tertiary and quaternary structure of TG is very important for hormone formation, a change in 1 of the 2 subunits (heterozygosity) may lead to severely impaired hormonogenesis of the heterodimeric TG and thus autosomal dominant inheritance of this disorder characterized by relatively high levels of abnormal TG. Van Ommen (1987) pointed out that the defects in the TG gene can cause either dominant or recessive disorders depending on the nature of the defect. When the gene is absent or at least when no thyroglobulin is synthesized, the disorder is likely to be recessive, whereas the presence of an abnormal subunit leads to a dominantly inherited disorder. The explanation for this is that in a dimeric protein such as thyroglobulin, 75% of the dimers in heterozygotes will contain 1 or more abnormal subunits. This should profoundly disturb thyroglobulin metabolism, since this protein fulfills a dual storage/catalytic role as a dimer, is present in bulk quantities (100 mg Tg/g thyroid mass), and needs to be exocytosed, iodinated, endocytosed, and degraded. INHERITANCE \- Autosomal recessive HEAD & NECK Neck \- Goiter NEUROLOGIC Central Nervous System \- Mental retardation (if untreated in infancy) ENDOCRINE FEATURES \- Hypothyroidism \- Euthyroid (compensated hypothyroidism) NEOPLASIA \- Thyroid cancer LABORATORY ABNORMALITIES \- Thyroid hormone coupling defect \- Excessive iodide trapping \- High FT3/FT4 ratio MOLECULAR BASIS \- Caused by mutation in the thyroglobulin gene (TG, 188450.0001 ) ▲ 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	THYROID DYSHORMONOGENESIS 3	c1848805	25,045	omim	https://www.omim.org/entry/274700	2019-09-22T16:21:41	{"mesh": ["C564766"], "omim": ["274400", "274700"], "orphanet": ["95716"], "synonyms": ["Thyroid dyshormonogenesis", "Alternative titles", "THYROID HORMONOGENESIS, GENETIC DEFECT IN, 3", "HYPOTHYROIDISM, CONGENITAL, DUE TO DYSHORMONOGENESIS, 3"]}
Congenital dyserythropoietic anemia is a hereditary disease that affects the production of red blood cells (erythropoiesis) and is characterized by anemia and problems in various organs. The signs and symptoms may include fatigue, weakness, pale skin, yellowing of the skin and eyes (jaundice), larger-than-normal liver and spleen (hepatosplenomegaly), and problems of the heart. There are four major types of the condition. Each type has a different cause and the additional signs and symptoms mentioned below: * Type 1: Characterized by moderate to severe anemia; jaundice; hepatosplenomegaly; and iron overload, which can lead to heart problems, liver disease (cirrhosis), and diabetes. Some people are born with skeletal defects of the fingers and/or toes. In some cases, the disease can be detected before birth as a hydrops fetalis. It is usually caused by changes (mutations) in the CDAN1 and C15orf41(less frequently) genes. * Type 2: Characterized by hepatosplenomegaly, gallbladder stones, and a milder form of anemia. After 20 years of age, some affected people develop iron overload. It is caused by mutations in the SEC23B gene * Type 3: The rarest form of the types. The liver is unaffected, but eye and blood problems (monoclonal gammopathy) are present. The exact cause of this type is currently unknown but it likely results from mutations in a gene located on the long arm of chromosome 15 at a position designated 15q22. * Type 4: Characterized by very severe anemia. It is caused by mutations in the KLF1 gene. Types 1 and 2 are inherited in an autosomal recessive manner. Type 3 appears to be inherited in an autosomal dominant manner. Type 4 is inherited in an autosomal dominant manner. Treatment may involve the use of a medication called interferon, and a bone marrow transplant. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Congenital dyserythropoietic anemia	c0002876	25,046	gard	https://rarediseases.info.nih.gov/diseases/1999/congenital-dyserythropoietic-anemia	2021-01-18T18:01:10	{"mesh": ["D000742"], "orphanet": ["85"], "synonyms": ["Dyserythropoietic anemia, congenital"]}
## Summary ### Clinical characteristics. CHMP2B frontotemporal dementia (CHMP2B-FTD) has been described in a single family from Denmark, in one individual with familial FTD from Belgium, and in one individual with FTD and no family history. It typically starts between ages 46 and 65 years with subtle personality changes and slowly progressive behavioral changes, dysexecutive syndrome, dyscalculia, and language disturbances. Disinhibition or loss of initiative is the most common presenting symptom. The disease progresses over a few years into profound dementia with extrapyramidal symptoms and mutism. Several individuals have developed an asymmetric akinetic rigid syndrome with arm and gait dystonia and pyramidal signs that may be related to treatment with neuroleptic drugs. Symptoms and disease course are highly variable. Disease duration may be as short as three years or longer than 20 years. ### Diagnosis/testing. The diagnosis of CHMP2B-FTD is established in a proband by identification of a heterozygous pathogenic variant in CHMP2B by molecular genetic testing. ### Management. Treatment of manifestations: Caregivers need information and psychological support to manage the behavioral changes and the loss of insight and judgment in affected individuals. Psychosocial support is essential and should include occupational therapy and environmental and physical interventions. Antipsychotics and/or antidepressants may improve physical aggressiveness. Administered antipsychotics should be reevaluated at short intervals with the goal of discontinuation as soon as feasible. ### Genetic counseling. CHMP2B-FTD is inherited in an autosomal dominant manner. Penetrance is age dependent and appears to be nearly complete; most individuals with CHMP2B-FTD have an affected parent. To date, de novo CHMP2B pathogenic variants have not been reported. Each child of an individual with CHMP2B-FTD has a 50% chance of inheriting the pathogenic variant. Once a CHMP2B pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing for CHMP2B-FTD are possible. ## Diagnosis ### Suggestive Findings CHMP2B frontotemporal dementia (CHMP2B-FTD) should be suspected in individuals with the following: * Frontotemporal dementia * A neuropsychological profile of a dysexecutive syndrome, behavioral changes, lack of emotional recognition, and dyscalculia * Generalized atrophy on neuroimaging: * Computed tomography (CT) or magnetic resonance imaging (MRI) show generalized cortical and central atrophy and ventricular enlargement [Gydesen et al 2002]. * Cerebral blood flow-positron emission tomography (CBF-PET) shows a global reduction in cortical CBF with sparing of the visual cortex and basal ganglia [Gydesen et al 2002]. * CBF-MRI shows a decreased CBF in occipital and parietal lobes in presymptomatic CHMP2B-FTD heterozygotes [Lunau et al 2012]. * Fluorodeoxyglucose (FDG)-PET shows globalized hypometabolism [Johannsen et al 2016]. * Family history of frontotemporal dementia in two or more first-degree relatives consistent with an autosomal dominant mode of inheritance * Neuropathology showing p62-positive, ubiquitin-positive, TDP-43-negative, and FUS-negative cytoplasmic intraneuronal inclusions in the hippocampal dentate granule cells and in neurons in the frontal and temporal cortex [Holm et al 2007, Holm et al 2009] ### Establishing the Diagnosis The diagnosis of CHMP2B-FTD is established in a proband by identification of a heterozygous pathogenic variant in CHMP2B by molecular genetic testing (see Table 1). Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing, multigene panel) and comprehensive genomic testing (exome sequencing, 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 CHMP2B-FTD is broad, 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 of familial FTD without neuropathology suggestive of CHMP2B-FTD are more likely to be diagnosed using genomic testing (see Option 2). #### Option 1 When the phenotypic and imaging findings suggest the diagnosis of CHMP2B-FTD, molecular genetic testing approaches can include single-gene testing or use of a multigene panel: * Single-gene testing. Sequence analysis of CHMP2B to detect small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. Note: Targeted analysis for CHMP2B pathogenic variant c.532-1G>C can be performed first in individuals of Danish ancestry [Skibinski et al 2005]. * A multigene panel that includes CHMP2B and other genes of interest (see Differential Diagnosis) may be considered to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) Given the rarity of CHMP2B-FTD some panels for dementia may not include this gene. (4) 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. (5) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. #### Option 2 When the phenotype is indistinguishable from many other inherited disorders characterized by frontotemporal dementia, comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is the best option. Exome sequencing is most commonly used; genome sequencing is also possible. 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 CHMP2B Frontotemporal Dementia View in own window Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method CHMP2BTargeted analysis for c.532-1G>CSee footnote 3. Sequence analysis 4All reported 3, 5 Gene-targeted deletion/duplication analysis 6Unknown 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\. The c.532-1G>C pathogenic variant in CHMP2B, a change in the acceptor site of exon 6, has been identified in a single large Danish kindred with frontotemporal dementia [Gydesen et al 2002, Skibinski et al 2005, Lindquist et al 2008]. 4\. 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. 5\. C-terminal truncations of CHMP2B appear to cause FTD [Skibinski et al 2005, Momeni et al 2006a, van der Zee et al 2008, Clayton et al 2015]. In one simplex case (i.e., a single occurrence in a family) a C-terminal truncation was reported [van der Zee et al 2008], while CHMP2B analysis in additional simplex cases and families with FTD evaluated for pathogenic variants [Cannon et al 2006, Rizzu et al 2006, Ghanim et al 2010] have only identified missense variants of uncertain significance [Isaacs et al 2011]. An apparently benign nonsense variant was identified in two unaffected members, but not identified in affected members of the same FTD family [Momeni et al 2006b]. 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\. No data on detection rate of gene-targeted deletion/duplication analysis are available. ## Clinical Characteristics ### Clinical Description CHMP2B frontotemporal dementia (CHMP2B-FTD) is an early-onset dementia affecting primarily frontal lobe functions. CHMP2B-FTD typically starts with subtle personality changes, behavioral changes, dyscalculia, and a dysexecutive syndrome [Stokholm et al 2013]. To date, CHMP2B-FTD has been described in a family that originates and resides in western Jutland, Denmark. The first description of this family was by Gydesen et al [1987]. CHMP2B-FTD has also been described in an affected individual with familial FTD from Belgium [van der Zee et al 2008]. In addition, one individual from the United Kingdom with FTD and no clear family history was reported to have a CHMP2B missense variant [Skibinski et al 2005]. Symptoms usually start between ages 46 and 70 years, with an average age of onset of 57 years. Disease duration is from three to more than 20 years. The disease progresses over a few years into profound dementia with mutism [Gydesen et al 2002, Brown et al 2004]. Behavioral changes. Disinhibition or loss of initiative is the most common presenting symptom. Affected individuals lose interest in their environment and neglect personal hygiene. The manifestations may vary from very disinhibited to very apathetic. Affected individuals may show inappropriate emotional responses and a lack of empathy. Hyperorality is common including overeating sweet foods and chain smoking. Restlessness is common. Aggressiveness and hypersexuality have been described. Lack of insight into illness is common. Stereotypic speech, pacing activity, and stereotypic behavioral routines are frequent [Gydesen et al 2002, Brown et al 2004]. Psychiatric symptoms. Psychotic symptoms are unusual, but it is difficult to determine if a very disinhibited person is psychotic. Some individuals develop depressive symptoms early in the illness; they are typically mild. Manic syndromes have been observed in a few individuals. Cognitive decline. Loss of executive function is a common early feature, as is dyscalculia and language impairment. Spontaneous speech declines, although repetition and reading from a text is relatively preserved. Perseveration, repetitive utterances, and echolalia are common. Affected individuals develop a nonfluent aphasia and then often become mute. Memory can be spared until late in the illness. Route finding and other visuospatial problems are unusual. Mini-Mental Status Examination (MMSE) scores are relatively preserved early in the disease, followed by a sharp decline with worsening aphasia [Gydesen et al 2002, Brown et al 2004, Stokholm et al 2013]. Extrapyramidal signs. Four years into the illness, several individuals have developed a striking motor syndrome that develops into an asymmetric akinetic rigid syndrome with arm and gait dystonia and pyramidal signs. This syndrome may be related to treatment with neuroleptic drugs [Gydesen et al 2002, Brown et al 2004]. Akinetic mutism has been observed in late stages of disease. Epilepsy. Generalized tonic-clonic epileptic seizures are rare in individuals with CHMP2B-FTD. Motor neuron disease. Severe motor neuron disease has not been described in individuals with CHMP2B-FTD; however, signs of lower motor neuron dysfunction (e.g., fasciculations) can be seen in the tongue or thigh muscles. Neuropathology. Macroscopic examinations find severe generalized atrophy with an asymmetric and frontal preponderance; brain weight is below 1000 g [Holm et al 2007]. Microscopic analysis reveals neuronal loss, gliosis, and spongiosis in the superficial cortical layers. Immunohistochemical analysis shows pathologic accumulation of p62-positive, ubiquitin-positive, TDP-43-negative, and FUS-negative cytoplasmic inclusions in the hippocampal dentate granule cells and in a few cortical neurons [Holm et al 2007, Holm et al 2009]. Consequently, the neuropathology is currently classified as frontotemporal lobar degeneration with inclusions positive for ubiquitin proteasome system markers [Mackenzie et al 2010, Mackenzie & Neumann 2016]. ### Genotype-Phenotype Correlations No genotype-phenotype correlations have been identified. ### Penetrance Penetrance is age dependent and appears to be nearly complete in the Danish family. ### Nomenclature CHMP2B-FTD was originally described as familial nonspecific dementia. Molecular genetic studies published by Brown et al [1995] demonstrated linkage of the disease-associated gene in the Danish family to the pericentromeric region of chromosome 3, leading to the designation chromosome 3-linked frontotemporal dementia (FTD3 or FTD-3). Following identification of a causative pathogenic variant in CHMP2B [Skibinski et al 2005], FTD3 is referred to as CHMP2B-associated frontotemporal dementia, CHMP2B-mediated frontotemporal dementia, or now CHMP2B-FTD. ### Prevalence CHMP2B-FTD has been described in one large Danish family [Gydesen et al 2002, Skibinski et al 2005], in one affected individual with familial FTD from Belgium [van der Zee et al 2008], and in one individual with FTD and no family history [Skibinski et al 2005]. ## Differential Diagnosis Pathogenic variants in CHMP2B have been identified in one large Danish family with frontotemporal dementia [Gydesen et al 2002, Skibinski et al 2005, Lindquist et al 2008] and in an affected individual with familial frontotemporal dementia (FTD) from Belgium [van der Zee et al 2008]. (A CHMP2B missense variant in one individual from the United Kingdom with FTD and no clear family history was also reported [Skibinski et al 2005]). Pathogenic variants in CHMP2B are considered to be a much rarer cause of frontotemporal dementia than pathogenic variants in MAPT (encoding tau), GRN (encoding progranulin), or C9orf72. ### Table 2. Genes of Interest in the Differential Diagnosis of CHMP2B Frontotemporal Dementia (CHMP2B-FTD) View in own window Gene(s)DisorderMOIClinical Features of Differential Diagnosis Disorder Overlapping w/CHMP2B-FTDDistinguishing from CHMP2B-FTD APP PSEN1 PSEN2 1Early-onset familial Alzheimer disease (EOFAD)AD * Mild behavioral changes * Prominent memory disturbance * Loss of initiative * Word-finding problems Absence of focal frontotemporal atrophy on neuroimaging C9orf72C9orf72-ALS/FTDADAdult-onset rapidly progressive features of FTD, ALS, or a combination of both * May not be clinically distinguishable * Psychotic symptoms more common in C9orf72-ALS/FTD FUSALS 6 w/or w/o FTDADMND w/FTD * Familial ALS w/o FTD * Onset before 5th decade * Incomplete penetrance GBA SNCA SNCBLewy body dementia (OMIM 127750)AD * Dementia * Extrapyramidal signs (rigidity, bradykinesia) * REM sleep disorders * Visual hallucinations * DaT scans abnormal GRNGRN-FTDAD * Adult-onset behavioral-variant FTD * Generally affects frontal & temporal cortex, → behavioral changes, executive dysfunction, & language disturbances * Parietal cortex & basal ganglia may be affected as well, resulting in parkinsonism, cortical basal syndrome, & memory impairment * Age of onset: 48-83 yrs * Clinically indistinguishable * Metabolic changes (on FDG-PET) preceding structural changes of frontal atrophy (on MRI) HTTHuntington diseaseAD * Changes in personality (apathy or depression) * Cognitive decline * Dementia * Dystonia * Chorea * Delusions * Visual hallucinations MAPTFTD w/parkinsonism-17 (OMIM 600274)AD * Adult-onset behavioral variant FTD * Extrapyramidal signs (rigidity, bradykinesia, supranuclear palsy, & saccadic eye movement disorders) * Symptoms usually start at ages 40-60 yrs but may occur earlier or later. * Disease progresses over few yrs to profound dementia w/mutism. * Clinically indistinguishable * Onset before 5th decade * Metabolic changes (on FDG-PET) preceding structural changes of frontal atrophy (on MRI) TARDBPTARDBP frontotemporal lobar degeneration (OMIM 612069)AD * Adult-onset behavioral variant FTD * Generalized cerebral atrophy on MRI * Early bulbar symptoms * Onset before 5th decade TBK1FTD &/or ALS 4 (OMIM 616439)AD * Adult-onset behavioral variant FTD * Disinhibition as presenting symptom * Generalized cerebral atrophy on MRI * Extrapyramidal features at later stage of disease * Memory loss at early stage of disease * Incomplete penetrance UBQLN2ALS 15 w/or w/o FTD (OMIM 300857)XL * MND w/FTD * Choreic movements * Familial ALS w/o FTD * Early spastic paralysis, dysarthria, & dysphagia * Onset before 5th decade VCPInclusion body myopathy with Paget disease of bone &/or FTDAD * Premature FTD * Early stages characterized by dysnomia, dyscalculia, comprehension deficits, paraphasic errors, & relative preservation of memory * Later stages characterized by inability to speak, auditory comprehension deficits for even 1-step commands, alexia, & agraphia * Mean age at FTD diagnosis: 56 yrs * Adult-onset proximal & distal muscle weakness 2 * Muscle weakness progresses to involve other limb & respiratory muscles. * Cardiac failure & cardiomyopathy may be observed in later stages. * Early-onset PDB 3 AD = autosomal dominant; ALS = amyotrophic lateral sclerosis; AR = autosomal recessive; FDG-PET = fluorodeoxyglucose-positron emission tomography; FTD = frontotemporal dementia; MND = motor neuron disease; MOI = mode of inheritance; PDB = Paget disease of bone; XL = X-linked 1\. It is likely that pathogenic variants in other genes causative of EOFAD will be identified because families with autosomal dominant FAD with no known pathogenic variants in PSEN1, PSEN2, or APP have been described [Pasanen et al 2018]. 2\. Adult-onset proximal and distal muscle weakness in inclusion body myopathy associated w/Paget disease of bone and/or FTD clinically resembles a limb-girdle muscular dystrophy syndrome. 3\. PDB involves focal areas of increased bone turnover that typically lead to spine and/or hip pain and localized enlargement and deformity of the long bones; pathologic fractures occur on occasion. Other considerations * Structural imaging may show a frontal preponderance of the generalized atrophy and will exclude other treatable causes of dementia (e.g., frontal meningioma, chronic subdural hematoma). * Nongenetic acquired causes of dementia should always be considered. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with CHMP2B frontotemporal dementia (CHMP2B-FTD), the following evaluations (if not performed as part of the evaluation that led to the diagnosis) are recommended: * A general medical history and family history * Physical and neurologic examination * Evaluation of the extent and profile of cognitive disturbance by neuropsychological examination * Discussion of capabilities for job and for driving * Consultation with a clinical geneticist and/or genetic counselor * Discussion of advanced care planning ### Treatment of Manifestations Behavioral changes and the loss of insight and judgment in individuals with CHMP2B-FTD often present a considerable burden for caregivers. Information about the disease and psychological support for partners or other caregivers is essential. Caregiver support groups are valuable. Psychosocial support is essential in the management of FTD and should include occupational therapy and environmental and physical interventions. The behavioral and psychological symptoms should be treated as in other types of FTD. There is no consensus treatment guideline for CHMP2B-FTD. In clinical practice those affected individuals who present with very aggressive symptoms have proven quite difficult to treat and in some instances have been treated with high doses of antipsychotics and/or antidepressants in order to relieve the physical aggressiveness. Administered antipsychotics should be reevaluated at short intervals with the goal of discontinuation as soon as feasible. ### Surveillance Members of the Danish family with CHMP2B-FTD are followed in the Copenhagen Memory Disorders Clinic, a multidisciplinary clinic involving neurologic and psychiatric services, genetic counseling, molecular genetic testing, and clinical diagnostic and follow-up medical service. ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for 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	CHMP2B Frontotemporal Dementia	c1833296	25,047	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1199/	2021-01-18T21:37:46	{"mesh": ["C579991"], "synonyms": ["CHMP2B-FTD", "Chromosome 3-Linked Frontotemporal Dementia", "FTD-3"]}
Sack–Barabas syndrome Other namesvEDS[1] This condition is inherited in an autosomal dominant manner Sack–Barabas syndrome is an older name for the medical condition Ehlers-Danlos syndrome, vascular type. It affects the body's blood vessels and organs, making them prone to rupture. ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 4 Treatment * 5 Epidemiology * 6 History * 7 See also * 8 References * 9 External links ## Signs and symptoms[edit] Patients with Sack–Barabas syndrome have thin, fragile skin, especially in the chest and abdomen, that bruises easily; hands and feet may have an aged appearance. Skin is soft but not overly stretchy. Facial features are often distinctive, including protruding eyes, a thin nose and lips, sunken cheeks, and a small chin. Other signs of the disorder include hypermobility of joints, tearing of tendons and muscles, painfully swollen veins in the legs, lung collapse, and slow wound healing following injury or surgery. Infants with the condition may be born with hip dislocations and clubfeet. Unpredictable ruptures of arteries and organs are serious complications of SBS. Ruptured arteries can cause internal bleeding, stroke, or shock, the most common cause of death in patients with this disorder. Rupture of the intestine is seen in 25 to 30 percent of affected individuals and tearing of the uterus during pregnancy affects 2 to 3 percent of women. Although these symptoms are rare in childhood, more than 80 percent of patients experience severe complications by the age of 40. Teenage boys are at high risk for arterial rupture, often being fatal. ## Causes[edit] Sack–Barabas is caused by mutations in the COL3A1 gene. * About half of all cases are inherited from a parent who has the condition. The condition is inherited in an autosomal dominant pattern, which means only one copy of the altered gene is necessary to cause the disorder. * The other half of cases occurs in patients whose families have no history of the disorder. These sporadic cases are caused by new mutations in one copy of the COL3A1 gene. The protein determined by the COL3A1 gene is used to assemble larger type III collagen molecules, found mostly in skin, blood vessels, and internal organs. When the structure or production of type III collagen is altered by a mutation in the COL3A1 gene, collagen fibrils cannot be assembled properly in these tissues, and the symptoms of Ehlers-Danlos syndrome result. ## Diagnosis[edit] The tests to verify Sack–Barabas syndrome are biochemical samples such as collagen typing (performed on a skin biopsy sample) or collagen gene mutation testing. There is no cure for Ehlers-Danlos syndrome, so individual problems and symptoms must be evaluated and cared for accordingly. ## Treatment[edit] The key for managing Sack–Barabas syndrome is for the affected person to be aware of their disease. Close follow up and planning of interventions can significantly prolong and maintain the quality of life of a person with this disease. Pregnant affected women must take special care due to the increased risk of premature death due to rupture of arteries, bowel or uterine rupture with a reported mortality rate of 50%. Genetic counseling is recommended for prospective parents with a family history of Ehlers–Danlos syndrome. Affected parents should be aware of the type of Ehlers-Danlos syndrome they have and its mode of inheritance. ## Epidemiology[edit] Sack–Barabas syndrome is rare and has an estimated prevalence of 1 in 100,000 to 200,000. The initial clinical manifestation of vascular problems in patients with SBS is early, about 25% have their first symptoms at age 20 and more than 80% of patients have had at least one complication by the age of 40. The median survival for one study of SBS patients was only 48 years. ## History[edit] The condition was originally named for German physician Georg Sack, who described a single case in 1936,[2] and British surgeon A.P. Barabas, who described two cases in 1967.[3] Barabas recognized that the condition was a form of Ehlers-Danlos syndrome, a group of inherited disorders affecting connective tissue. This condition is now called Ehlers–Danlos syndrome, vascular type [formerly EDS type IV]. ## See also[edit] * Ehlers–Danlos syndrome ## References[edit] 1. ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Vascular Ehlers Danlos syndrome". www.orpha.net. Retrieved 30 October 2019. 2. ^ Sack G (1936). "Status Dysvascularis, ein Fall von besonderer Zerreis-slichkeit der Blutgefässe". Deutsches Archiv für Klinische Medizin. 178: 663–669. 3. ^ Barabas A.P. (1967). "Heterogeneity of the Ehlers-Danlos Syndrome: Description of Three Clinical Types and a Hypothesis to Explain the Basic Defect(s)" (PDF). British Medical Journal. 2 (5552): 612–3. doi:10.1136/bmj.2.5552.612. PMC 1842124. PMID 6025600. ## External links[edit] Classification D * ICD-10: Q79.6 * OMIM: 130050 External resources * Orphanet: 286 * eds4 at NIH/UW GeneTests * 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	Sack–Barabas syndrome	c0268338	25,048	wikipedia	https://en.wikipedia.org/wiki/Sack%E2%80%93Barabas_syndrome	2021-01-18T19:05:37	{"gard": ["2082"], "mesh": ["D004535"], "umls": ["C0268338"], "orphanet": ["286"], "wikidata": ["Q3508605"]}
Pacemaker failure is the inability of an implanted artificial pacemaker to perform its intended function of regulating the beating of the heart. A pacemaker uses electrical impulses delivered by electrodes in order to contract the heart muscles.[1] Failure of a pacemaker is defined by the requirement of repeat surgical pacemaker-related procedures after the initial implantation. Most implanted pacemakers are dual chambered and have two leads, causing the implantation time to take longer because of this more complicated pacemaker system. These factors can contribute to an increased rate of complications which can lead to pacemaker failure.[2] Approximately 2.25 million pacemakers were implanted in the United States between 1990 and 2002, and of those pacemakers, about 8,834 were removed from patients because of device malfunction most commonly connected to generator abnormalities.[3] In the 1970s, results of an Oregon study indicated that 10% of implanted pacemakers failed within the first month.[4] Another study found that more than half of pacemaker complications occurred during the first 3 months after implantation.[2] Causes of pacemaker failure include lead related failure, unit malfunction, problems at the insertion site, failures related to exposure to high voltage electricity or high intensity microwaves, and a miscellaneous category (one patient had ventricular tachycardia when using his electric razor and another patient had persistent pacing of the diaphragm muscle).[4] Pacemaker malfunction has the ability to cause serious injury or death, but if detected early enough, patients can continue with their needed therapy once complications are resolved.[3] ## Contents * 1 Symptoms[5] * 2 Causes * 2.1 Direct factors * 2.2 Indirect factors * 3 Prevention[5] * 4 Treatment[5] * 5 See also * 6 References ## Symptoms[5][edit] * Moderate dizziness or lightheadedness * Syncope * Slow or fast heart rate * Discomfort in chest area * Palpitations * Hiccups ## Causes[edit] ### Direct factors[edit] * Lead dislodgement * A Macro-dislodgement is radiographically visible.[5] * A Micro-dislodgement is a minimal displacement in the lead that is not visible in a chest X-ray, but has the ability to increase the capture threshold and eventually cause a loss of capture.[5] * Lead dislodgement can cause sensing failure, which occurs when proper atrial or ventricular sensing is not achieved by the programming of the pacemaker. Ventricular lead dislodgement is less common compared to atrial lead dislodgement.[2] * Causes * Twiddler's Syndrome * The patient's constant manipulation of the pulse generator within its skin pocket can lead to a dislodgement of the device.[6] The generator is rotated on its longitudinal axis, which causes traction and results in a lead dislodgement.[5] * Reel's Syndrome * Like Twiddler's Syndrome, it is the manipulation of the pulse generator, but instead the generator is rotated on its transverse axis, which rolls the lead around the generator, creating dislodgement.[5] * Direct trauma over the system.[5] * Lead fracture[2] * Unit malfunction * Battery failure, component malfunction, or generator failure[4] * Problems at the insertion site * Infection of the insertion site can cause local inflammation or the formation of an abscess in the pulse generator pocket.[2] * Infection can cause the erosion of part of the pacing system that is in the skin.[2] * Failures related to exposure to high voltage electricity or high intensity microwaves[4] ### Indirect factors[edit] * Power-generating equipment, arc welding equipment and powerful magnets (as in medical devices, heavy equipment or motors) can inhibit pulse generators. Patients who work with or near such equipment should know that their pacemakers may not work properly in those conditions.[7] * With the advances of technology, Federal Communications Commission (FCC) is making new frequencies available. Cellphones using these new frequencies might make pacemakers less reliable. A group of cellphone companies is studying that possibility.[7] * Equipment used by doctors and dentists can affect pacemakers.[7] * Magnetic resonance imaging (MRI) uses a powerful magnet to produce images of internal organs and their functions. Metal objects are attracted to the magnet and are normally not allowed near MRI machines. The magnet can interrupt the pacing and inhibit the output of pacemakers. If MRI must be done, the pacemaker output in some models can be reprogrammed.[7] In February 2011, the FDA approved an MRI-safe pacemaker.[8] * Extracorporeal shock-wave lithotripsy (ESWL) procedure is safe for most pacemaker patients, with some reprogramming of the pacing. Careful follow-up after the procedure is required. Patients with certain kinds of pacemakers implanted in the abdomen should avoid ESWL.[7] * Diagnostic radiation (such as screening X-ray) appears to have no effect on pacemaker pulse generators. However, therapeutic radiation (such as for treating cancerous tumors) may damage the pacemaker's circuits. The degree of damage is unpredictable and may vary with different systems. However, the risk is significant and builds up as the radiation dose increases. The American Heart Association recommends that the pacemaker be shielded as much as possible, and moved if it lies directly in the radiation field.[7] * Short-wave or microwave diathermy uses high-frequency, high-intensity signals. These may bypass pacemaker's noise protection and interfere with or permanently damage the pulse generator.[7] ## Prevention[5][edit] * Lead displacement * Adequate surgical implantation. * Usage of active fixation leads. * Verification of lead position 24–48 hours implantation. ## Treatment[5][edit] * Lead displacement * Early displacements: surgical repositioning of the lead or lead repositioning via percutaneous access. * Late displacements: implanting a new lead in the chamber where displacement has occurred. ## See also[edit] * Pacemaker crosstalk ## References[edit] 1. ^ McWilliam, John A. (1889-02-16). "Electrical Stimulation of the Heart in Man". Br Med J. 1 (1468): 348–350. doi:10.1136/bmj.1.1468.348. ISSN 0007-1447. PMC 2154721. PMID 20752595. 2. ^ a b c d e f Kiviniemi, Mikko S.; Pirnes, Markku A.; Eränen, H. Jaakko K.; Kettunen, Raimo V.j.; Hartikainen, Juha E.k. (1999-05-01). "Complications Related to Permanent Pacemaker Therapy". Pacing and Clinical Electrophysiology. 22 (5): 711–720. doi:10.1111/j.1540-8159.1999.tb00534.x. ISSN 1540-8159. PMID 10353129. S2CID 13076829. 3. ^ a b "Pacemakers malfunction less often than defibrillators". AORN Journal. 82: 862. 2005 – via Gale Health Reference Center Academic. 4. ^ a b c d Reinhart, Steven; McAnulty J; Dobbs J (April 1981). "Type and timing of permanent pacemaker failure". Chest. 81 (4): 433–5. doi:10.1378/chest.81.4.433. PMID 7067508. Retrieved 2009-09-08. 5. ^ a b c d e f g h Fuertes, Beatriz; Toquero, Jorge; Arroyo-Espliguero, Ramon; Lozano, Ignacio F (2003-10-01). "Pacemaker Lead Displacement: Mechanisms And Management". Indian Pacing and Electrophysiology Journal. 3 (4): 231–238. ISSN 0972-6292. PMC 1513524. PMID 16943923. 6. ^ Salahuddin, Mohammad; Cader, Fathima Aaysha; Nasrin, Sahela; Chowdhury, Mashhud Zia (2016-01-01). "The pacemaker-twiddler's syndrome: an infrequent cause of pacemaker failure". BMC Research Notes. 9: 32. doi:10.1186/s13104-015-1818-0. ISSN 1756-0500. PMC 4721019. PMID 26790626. 7. ^ a b c d e f g "Pacemakers". American Heart Association. Retrieved 6 April 2011. 8. ^ Miller, Reed (9 February 2011). "FDA approves first "MRI-safe" pacemaker". theheart.org. Retrieved 4 April 2011. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Pacemaker failure	c0281929	25,049	wikipedia	https://en.wikipedia.org/wiki/Pacemaker_failure	2021-01-18T18:48:13	{"umls": ["C0281929"], "wikidata": ["Q17004153"]}
Beta-propeller protein-associated neurodegeneration (BPAN) is a disorder that damages the nervous system and is progressive, which means that it gradually gets worse. Affected individuals develop a buildup of iron in the brain that can be seen with medical imaging. For this reason, BPAN is classified as a type of disorder called neurodegeneration with brain iron accumulation (NBIA), although the iron accumulation may not occur until late in the disease. Many people with BPAN have recurrent seizures (epilepsy) beginning in infancy or early childhood. Several different types of seizures can occur in this disorder, even in the same individual. Often the first type to occur are febrile seizures, which are triggered by a high fever. Affected individuals can also experience generalized tonic-clonic seizures (also known as grand mal seizures). This type of seizure affects the entire body, causing muscle rigidity, convulsions, and loss of consciousness. Other seizure types that can occur in this disorder include short lapses in awareness that can have the appearance of staring spells or daydreaming (absence seizures, also called petit mal seizures), sudden episodes of weak muscle tone (atonic seizures), involuntary muscle twitches (myoclonic seizures), or more pronounced movements called epileptic spasms. Some individuals have seizure patterns that resemble those in epileptic syndromes, such as West syndrome or Lennox-Gastaut syndrome. Children with BPAN also have intellectual disability, delayed development including significant problems with vocabulary and producing speech (expressive language), and difficulty coordinating movements (ataxia). Ataxia can affect the ability to walk and perform fine motor skills such as using utensils. Affected individuals can have behavioral changes that are often compared to features of a disorder called Rett syndrome. These features include repeated hand wringing or clasping (stereotypic hand movements); teeth grinding (bruxism); sleep disturbances; and problems with communication and social interaction characteristic of autism spectrum disorder. In late adolescence or early adulthood, individuals with BPAN may begin to experience a gradual loss of intellectual functioning (cognitive decline) that can lead to a severe loss of thinking and reasoning abilities (dementia). Worsening problems with movement also occur, including dystonia and parkinsonism. Dystonia is a condition characterized by involuntary, sustained muscle contractions. In BPAN, the dystonia often starts in the arms. Parkinsonism can include unusually slow movement (bradykinesia), rigidity, tremors, an inability to hold the body upright and balanced (postural instability), and a shuffling walk that can cause recurrent falls. The lifespan of people with BPAN varies. With proper management of their signs and symptoms, affected individuals can live into middle age. Death may result from complications of dementia or movement problems, such as injuries from falls or swallowing difficulties (dysphagia) that can lead to a bacterial lung infection called aspiration pneumonia. ## Frequency BPAN is a rare disorder. Its prevalence is unknown, but it is thought to account for between 35 and 40 percent of all cases of NBIA disorders. Some individuals who have been diagnosed with intellectual disability or early-onset parkinsonism based on their signs and symptoms have later been found to have BPAN when genetic testing was done. ## Causes BPAN is caused by mutations in the WDR45 gene. This gene provides instructions for making the WIPI4 protein. WIPI4 has a characteristic structure resembling a seven-bladed propeller, from which the name of the disorder is derived. The WIPI4 protein is involved in a process called autophagy, which helps clear unneeded materials from cells, including excess amounts of an iron storage protein called ferritin. Most of the WDR45 gene mutations identified in people with BPAN result in the absence of functioning WIPI4 protein. As a result, the process of autophagy is impaired, making cells less efficient at removing damaged cell structures and waste materials. Researchers suggest that nerve cells (neurons) may be particularly vulnerable to impaired autophagy because they have long extensions (axons and dendrites), making it even more difficult to transport the waste materials from these structures to the compartments in the cell body where recycling takes place (the lysosomes). The waste materials can build up in these areas and damage them. Damage to neurons results in the neurological problems that occur in BPAN. ### Learn more about the gene associated with Beta-propeller protein-associated neurodegeneration * WDR45 ## Inheritance Pattern This condition is inherited in an X-linked dominant pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. In most X-linked dominant disorders, males experience more severe symptoms than females. While this is not always the case in BPAN, most individuals with the disorder are females, likely because a smaller number of affected males survive until birth. Almost all cases of BPAN result from new mutations in the gene and occur in people with no history of the disorder in their family. Rarely, an affected person inherits the mutation from a mildly affected mother. Among reported cases, males with BPAN and most females with BPAN have not had children. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Beta-propeller protein-associated neurodegeneration	c3550973	25,050	medlineplus	https://medlineplus.gov/genetics/condition/beta-propeller-protein-associated-neurodegeneration/	2021-01-27T08:25:34	{"gard": ["12570"], "omim": ["300894"], "synonyms": []}
See also: brain stem glioma Main article: brain tumors A brain stem tumor is a tumor in the part of the brain that connects to the spinal cord (the brain stem). ## Contents * 1 Symptoms * 2 Diagnosis * 2.1 Types of brain stem tumors * 3 Treatment * 4 Prognosis * 5 References * 6 External links ## Symptoms[edit] The symptoms of brain stem tumors vary greatly and can include ataxia, cranial nerve palsy, headaches, problems with speech and swallowing, hearing loss, weakness, hemiparesis, vision abnormalities, ptosis, and behavioral changes. Another possible symptom is vomiting. Headaches related to brainstem tumors may be worse shortly after waking up in the morning.[1] ## Diagnosis[edit] An MRI is better than a CT scan when a brainstem tumor is in the differential diagnosis. ### Types of brain stem tumors[edit] The most common form of brainstem tumor is the brainstem glioma. ## Treatment[edit] Treatment typically consists of radiotherapy and steroids for palliation of symptoms.[citation needed] (Proton Beam Therapy should be included here by someone with good knowledge of it; it is more accurate, and very importantly for pediatric cases, has reduced side effects.) Radiotherapy may result in minimally extended survival time.[citation needed] ## Prognosis[edit] Prognosis is very poor, with only 37% of treated patients surviving one year or more.[citation needed] Topotecan has been studied in the treatment of brainstem glioma,[citation needed] otherwise, chemotherapy is probably ineffective, though further study is needed.[2] ## References[edit] 1. ^ http://neurosurgery.mgh.harvard.edu/abta/primer.htm[full citation needed] 2. ^ Brainstem Gliomas~treatment at eMedicine ## External links[edit] * Brain stem tumor entry in the public domain NCI Dictionary of Cancer Terms This article incorporates public domain material from the U.S. National Cancer Institute document: "Dictionary of Cancer Terms". This oncology article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Brain stem tumor	c0677866	25,051	wikipedia	https://en.wikipedia.org/wiki/Brain_stem_tumor	2021-01-18T18:39:52	{"mesh": ["D020295"], "umls": ["C0677866"], "wikidata": ["Q4955836"]}
Sheldon-Hall syndrome, also known as distal arthrogryposis type 2B, is characterized by joint deformities (contractures) that restrict movement in the hands and feet. People with this condition may also have distinctive facial features, extra folds of skin on the neck, and short stature. Intelligence and life expectancy are not usually affected. Sheldon-Hall syndrome can be caused by mutations in the MYH3, TNNI2, TNNT3, or TPM2 gene. It is inherited in an autosomal dominant pattern. In about 50% of cases, an affected person inherits the mutation from an affected parent. Other cases result from a new mutation in the gene and occur in people with no family history of the disorder. While there is no specific treatment for this condition, occupational and physical therapy, serial casting, and/or surgery may benefit those who are affected. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Sheldon-Hall syndrome	c1834523	25,052	gard	https://rarediseases.info.nih.gov/diseases/9909/sheldon-hall-syndrome	2021-01-18T17:57:44	{"mesh": ["C538400"], "omim": ["601680"], "orphanet": ["1147"], "synonyms": ["DA2B", "Arthrogryposis multiplex congenita distal type 2B", "Freeman Sheldon syndrome, variant", "Arthrogryposis multiplex congenita distal type II with craniofacial abnormalities", "Distal arthrogryposis type IIB", "Freeman-Sheldon syndrome variant", "Freeman Sheldon variant", "Distal arthrogryposis type 2B"]}
A rare constitutional hemolytic anemia characterized in symptomatic forms by mild to severe chronic hemolysis, which is further exacerbated by oxidative stress and may lead to chronic non-sperocytic hemolytic anemia of variable severity. Variation in glucose-6-phosphate dehydrogenase levels accounts for differences in sensitivity to oxidants, with chronic hemolysis occurring in association with very low enzyme levels, while the majority of affected individuals remain asymptomatic. The most common clinical manifestations are neonatal jaundice and signs and symptoms of acute hemolysis (such as fatigue, back pain, anemia, and jaundice). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Class I glucose-6-phosphate dehydrogenase deficiency	c2720289	25,053	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=466026	2021-01-23T17:35:43	{"mesh": ["C567533"], "omim": ["300908"], "icd-10": ["D55.0"], "synonyms": ["Class I G6PD deficiency", "Severe hemolytic anemia due to G6PD deficiency"]}
A number sign (#) is used with this entry because of evidence that alopecia-mental retardation syndrome-1 (APMR1) is caused by homozygous mutation in the AHSG gene (138680) on chromosome 3q27. One such family has been reported. Description Alopecia-mental retardation syndrome (APMR) is a rare autosomal recessive disorder in which affected individuals show loss of hair on the scalp, absence of eyebrows, eyelashes, and axillary and pubic hair, and mild to severe mental retardation (summary by Wali et al., 2007). ### Genetic Heterogeneity of Alopecia-Mental Retardation Syndrome Loci for alopecia-mental retardation syndrome have been mapped to chromosome 3q26.2-q26.31 (APMR2; 610422) and chromosome 18q11.2-q12.2 (APMR3; 613930). Clinical Features Baraitser et al. (1983) reported the combination of alopecia from birth and mental retardation in 3 cousins, each in a different sibship of an inbred Middle Eastern family. The alopecia was total and involved all areas of normal hair growth. Mental retardation was severe. A similar condition was described by Perniola et al. (1980) in 2 sibs of consanguineous parents. Both sibs were deaf. Benke and Hajianpour (1985) described an inbred Pakistani family in which 3 consanguineous couples had a child with this combination. Hearing, teeth, nails, bone x-rays, and sweating were normal and the patients were not dysmorphic. The Amish hair-brain syndrome (234050) has mild mental retardation and associated short stature; the affected persons have hair which is brittle and falls out. Reza Sailani et al. (2017) reported a large consanguineous Iranian family in which 8 individuals spanning 4 generations had APMR. Specific clinical details were not provided, but all affected individuals had alopecia and intellectual disability with an IQ ranging from 40 to 54. Mapping John et al. (2006) ascertained a large consanguineous kindred from a remote region in Pakistan with multiple individuals affected by alopecia and severe mental retardation. A genomewide scan mapped the disease locus to 3q26.33-q27.3. A maximum 2-point lod score of 3.05 (theta = 0.0) was obtained at marker D3S3583. Molecular Genetics In 7 affected members of a large consanguineous Iranian family with APMR1, Reza Sailani et al. (2017) identified a homozygous missense mutation in the AHSG gene (R317H; 138680.0004). The mutation occurred at a highly conserved residue in the propeptide within a phosphorylation motif that is proteolytically processed posttranslationally to yield the mature protein. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The findings were also confirmed by linkage analysis in the family. The mutation was predicted to alter protein phosphorylation, and Western blot analysis and immunoprecipitation studies of serum showed that those with the homozygous mutation had an altered AHSG protein size, whereas those who were heterozygous carriers of the mutation had only a single normal protein band. Reza Sailani et al. (2017) speculated that the R317H mutation would disrupt phosphorylation or glycosylation sites needed for proper protein function. INHERITANCE \- Autosomal recessive SKIN, NAILS, & HAIR Hair \- Alopecia, complete NEUROLOGIC Central Nervous System \- Mental retardation, severe MISCELLANEOUS \- One consanguineous Iranian family with a confirmed AHSG mutation has been reported (last curated January 2018) MOLECULAR BASIS \- Caused by mutation in the alpha-2-HS-glycoprotein gene (AHSG, 138680.0004 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	ALOPECIA-MENTAL RETARDATION SYNDROME 1	c2931280	25,054	omim	https://www.omim.org/entry/203650	2019-09-22T16:31:12	{"mesh": ["C536660"], "omim": ["203650"], "orphanet": ["2850"], "synonyms": ["Alternative titles", "APMR", "AMR SYNDROME"]}
2001 Japan Airlines mid-air incident 日本航空機駿河湾上空ニアミス事故Accident DateJanuary 31, 2001 (2001-01-31) SummaryNear miss, ATC error Sitenear Yaizu, Shizuoka, Japan Total fatalities0 Total injuries100 (All on Japan Airlines Flight 907) Total survivors677 (all) First aircraft JA8904, the aircraft involved seen in 2004. TypeBoeing 747-446D OperatorJapan Airlines RegistrationJA8904[1] Flight originTokyo Int'l Airport, Tokyo, Japan DestinationNaha Int'l Airport, Okinawa, Japan Occupants427 Passengers411 Crew16 Fatalities0 Injuries100 (9 serious, 91 minor) Survivors427 (all) Second aircraft A Japan Airlines DC-10, similar to the aircraft involved. TypeMcDonnell Douglas DC-10-40 OperatorJapan Airlines RegistrationJA8546[1] Flight originGimhae International Airport, Busan, South Korea DestinationNarita International Airport, Tokyo, Japan Occupants250 Passengers237 Crew13 Fatalities0 Injuries0 Survivors250 (all) On January 31, 2001, Japan Airlines Flight 907, a Boeing 747-400 en route from Haneda Airport, Japan, to Naha Airport, Okinawa, narrowly avoided a mid-air collision with Japan Airlines Flight 958, a McDonnell Douglas DC-10-40 en route from Gimhae International Airport, South Korea, to Narita International Airport, Japan. The event became known in Japan as the Japan Airlines near miss incident above Suruga Bay (日本航空機駿河湾上空ニアミス事故, Nihonkōkūki surugawan jōkū niamisu jiko). The incident was attributed to errors made by Air Traffic Controller (ATC) trainee Hideki Hachitani (蜂谷秀樹, Hachitani Hideki) and trainee supervisor Yasuko Momii (籾井康子, Momii Yasuko). The incident caused Japanese authorities to call upon the International Civil Aviation Organization (ICAO) to take measures to prevent similar incidents from occurring. ## Contents * 1 Flight information * 2 Mid-air incident * 3 Aftermath * 3.1 Criminal investigation and trial * 4 In popular culture * 5 See also * 6 Notes * 7 References * 8 External links ## Flight information[edit] The Boeing 747-446 Domestic, registration JA8904, was operating Flight 907 from Tokyo Haneda International Airport to Naha Airport with 411 passengers and 16 crew. The flight departed Haneda airport at 15:36 local time. Flight 907 was commanded by 40-year-old pilot Makoto Watanabe (渡辺誠, Watanabe Makoto). The McDonnell Douglas DC-10-40, registration JA8546, was operating Flight 958 from Gimhae International Airport to Narita International Airport with 237 passengers and 13 crew.[2] Flight 958 was commanded by 45-year-old pilot Tatsuyuki Akazawa (赤沢達幸, Akazawa Tatsuyuki). According to the flight plan, both aircraft were supposed to pass each other while 2,000 feet apart.[3] ## Mid-air incident[edit] The mid-air incident occurred as flight attendants began to serve drinks onboard Flight 907.[4] JA8904's 'Traffic Collision Avoidance System (TCAS)‘ sounded 20 minutes after its departure[3] as the jet climbed towards 39,000 feet. The DC-10, JA8546, cruised at 37,000 feet.[2] The TCAS on both aircraft functioned correctly, a "CLIMB" instruction was annunciated for Flight 907, however the flight crew received contradicting instructions from the flight controller at the Tokyo Area Control Center in Tokorozawa, Saitama Prefecture. Flight 907 followed an order to descend issued by the flight controller while Flight 958 descended as instructed by the TCAS, meaning that the planes remained on a collision course. The trainee for the aerospace sector, 26-year-old[5] Hideki Hachitani (蜂谷秀樹, Hachitani Hideki),[6] handled ten other flights at the time of the near miss. Hachitani intended to tell Flight 958 to descend. Instead, at 15:54, he told Flight 907 to descend. When the trainee noticed that JAL 958 cruised at a level altitude instead of descending, the trainee asked JAL 958 to turn right; the message did not get through to the JAL 958 pilot. The trainee's supervisor, Yasuko Momii (籾井康子, Momii Yasuko),[7] ordered "JAL 957" to climb, intending to tell JAL 907 to climb. There was not a JAL flight 957 in the sky at the moment of the incident, but it can be inferred that by "957" she meant flight 907.[2] The aircraft avoided collision using evasive maneuvers once they were in visual proximity, and passed within about 135 metres (443 ft) of each other.[a][9] An unidentified passenger told NHK, "I have never seen a plane fly so close. I thought we were going to crash." Alex Turner, a passenger on Flight 907 and a student at Kadena High School, a school for American children with parents stationed at Kadena Air Base in Okinawa Prefecture, estimated that the avoidance maneuver lasted for two seconds.[3] Seven passengers and two crew members of the 747 sustained serious injuries; additionally, 81 passengers and 10 crew members reported minor injuries. Some unbelted passengers, flight attendants, and drink carts hit the ceiling, dislodging some ceiling tiles.[4] The maneuver threw one boy across four rows of seats.[3] Most of the injuries to occupants consisted of bruising. The maneuvers broke the leg of a 54-year-old woman.[10][11] In addition, a drink cart spilled, scalding some passengers. No passengers on the DC-10 sustained injuries.[12] Flight 907, with the 747's cabin bearing minor damage, returned to Haneda, landing at 16:45. ## Aftermath[edit] JAL907 injury chart By 18:00 on February 1, eight Flight 907 passengers remained hospitalized, while 22 injured passengers had been released. Two passengers remained hospitalized at Kamata General Hospital (蒲田総合病院). Two passengers remained hospitalized at Ichikawa No. 2 Hospital (市川第2病院). In addition, the following hospitals each had one passenger remaining: Takano Hospital (タカノ病院), Kitasato University, Horinaka Hospital (堀中病院), and Tokyo Rosai Hospital (東京労災病院).[13] All injured passengers recovered. JAL sent apology letters to the passengers on the 747; injured passengers directly received messages, and uninjured passengers received messages via the mail.[14] In its report on the accident, published in July 2002, the Aircraft and Railway Accidents Investigation Commission called on the International Civil Aviation Organization (ICAO) to make it clear that TCAS advisories should always take precedence over ATC instructions.[15] A similar recommendation was made three months later by Germany's accident investigation body (the BFU) in light of the Überlingen mid-air collision.[16] ICAO accepted these recommendations and amended its regulations in November 2003.[17][18] Flight numbers 907 and 958 are still used by Japan Airlines for the same respective routes today, but are operated with a Boeing 777 and Boeing 737, respectively. ### Criminal investigation and trial[edit] The Tokyo Metropolitan Police Department and Ministry of Land, Infrastructure and Transport investigated the incident.[9] In May 2003, Tokyo police filed an investigative report concerning Hideki Hachitani (ATC trainee), Yasuko Momii (ATC Supervisor), and Makoto Watanabe (Pilot of flight 907), suspecting them of professional negligence. In March 2004, prosecutors indicted Hachitani and Momii for professional negligence.[19] Hachitani, then 30 years old, and Momii, then 35 years old, pleaded not guilty to the charges at Tokyo District Court in 2004.[20] During the same year, the lawyer for Hachitani and Momii said that the pilots of the aircraft bore the responsibility for the near miss.[21] By November 16, 2005, 12 trials had been held since the initial hearing on September 9, 2004. The prosecution argued that the two defendants neglected to provide proper separation for the two aircraft, the instructions issued were inappropriate, and that the supervisor failed to correct the trainee. The defense argued that the lack of separation would not immediately have led to a near miss, that the instructions issued were appropriate, that the TCAS procedure was not proper, and that the Computer Navigation Fix (CNF) had faulty data.[22] In 2006, prosecutors asked for Hachitani, then 31, to be sentenced to ten years in prison and for Momii, then 37, to be sentenced to 15 years in prison.[23] On March 20, 2006 the court ruled that Hachitani and Momii were not guilty of the charge.[6][24][25] The court stated that Hachitani could not have foreseen the accident and that the mixup of the flight numbers did not have a causal relationship with the accident. Hisaharu Yasui, the presiding judge, said that prosecuting controllers and pilots would be "unsuitable" in this case.[26] The Tokyo District Public Prosecutor's Office filed an appeal with the Tokyo High Court on March 31. During the same year, the Japanese government agreed to pay Japan Airlines and Tokio Marine & Nichido Fire Insurance a total of ¥82.4 million to compensate for the near miss (equivalent to ¥86 million in 2019).[27] On April 11, 2008, on appeal, a higher court overturned the decision and found Hachitani and Momii guilty. The presiding judge, Masaharu Suda (須田賢, Suda Masaharu), sentenced Hachitani, then 33, to 12 months imprisonment, and Momii, then 39, for 18 months imprisonment, with both sentences suspended for 3 years. [25] The lawyers representing the controllers appealed, but the convictions were upheld on October 26, 2010 by the Supreme Court.[28] [29] ## In popular culture[edit] The events of the incident are documented in the final season 3 episode of the Discovery Channel documentary Aircrash Confidential.[30] The episode was first aired on 20 August 2018. ## See also[edit] * Japan portal * Aviation portal * Überlingen mid-air collision, mid-air collision in 2002 also attributed to conflicting ATC and TCAS messages * 1996 Charkhi Dadri mid-air collision ## Notes[edit] 1. ^ The closest passing distance was estimated by the investigation team from an analysis of the TCAS logs.[8] ## References[edit] 1. ^ a b Tomita, Hiroaki (Investigator General, Aircraft and Railway Accidents Investigation Commission). "Accident Investigation into a Near Mid-Air Collision." June 12, 2005 (Queenstown, New Zealand). 2. ^ a b c "Blame pinned on air traffic controllers[permanent dead link]." Japan Times. Saturday February 3, 2001. Retrieved on December 11, 2009. 3. ^ a b c d Childs, Jan Wesner (February 2, 2001). "Kadena High students shaken by near-miss during flight over Japan". Stars and Stripes. Archived from the original (Web) on 2009-04-22. Retrieved December 11, 2009. 4. ^ a b "JAL planes almost collide Archived January 5, 2008, at the Wayback Machine," Yomiuri Shimbun. Retrieved on December 11, 2009. 5. ^ "Controllers blamed for near-miss." BBC. Friday February 2, 2001. Retrieved on December 11, 2009. 6. ^ a b "Court finds air traffic controllers not guilty over 2001 near miss." Kyodo World News Service. 7. ^ "Court clears air controllers in near miss". Yomiuri Shimbun, March 21, 2006. 8. ^ Final report section 3.2.6 9. ^ a b Schaefer, Gary (February 3, 2001). "Japanese police pursuing possibility of negligence in planes' near collision". Stars and Stripes. The Associated Press. Archived from the original (Web) on 2008-01-05. 10. ^ "Shigeyoshi Kimura, Associated Press Writer (January 31, 2001). "At least 35 airline passengers injured in near miss". 11. ^ "Close Call For JAL Jets." CBS News. January 31, 2001. Retrieved on December 11, 2009. 12. ^ "Signals blamed for near collision." BBC. Thursday February 1, 2001. Retrieved on December 11, 2009. 13. ^ "JL907便事故について" (Japanese). Japan Airlines. Retrieved on December 25, 2008. 14. ^ "Japan Airlines apologises to near-miss victims." Airline Industry Information. February 9, 2001. Retrieved on December 11, 2009. 15. ^ "report outline". International Civil Aviation Organization. Archived from the original on September 29, 2007. Retrieved 2007-01-22. 16. ^ "Investigation Report AX001-1-2" (PDF). German Federal Bureau of Aircraft Accidents Investigation. 2 May 2004. p. 111. Archived (PDF) from the original on 23 January 2007. Retrieved 17 January 2007. <references></references> 17. ^ Flight Safety Digest, March 2004 18. ^ "Deadly Crossroads," Mayday 19. ^ "Not guilty verdict revoked, 2 air controllers given suspended sentences\|date=February 20, 2009." Associated Press. April 11, 2008. Retrieved on December 11, 2009. 20. ^ "2 air controllers in 2001 JAL near-miss accident plead not guilty.." Japan Transportation Scan. September 9, 2004. Retrieved on December 11, 2009. 21. ^ "2 air-traffic controllers blame JAL pilots for near-miss.." Asia Africa Intelligence Wire. September 10, 2004. Retrieved on December 11, 2009. 22. ^ "REPORT OF THE JAPAN AIR TRAFFIC CONTROLLERS’ ASSOCIATIONS (JFATCA) To The 22nd IFATCA Asia Pacific Regional Meeting, Fukuoka, Japan (16-18 November 2005)[permanent dead link]." Air Traffic Control Association Japan. Retrieved July 17, 2008.[dead link] 23. ^ "Air traffic controllers face prison terms over 2001 near miss.." Japan Transportation Scan. 24. ^ "Court finds air traffic controllers not guilty over 2001 near miss[permanent dead link]." Japan Today. 25. ^ a b "Not guilty verdict revoked, 2 air controllers given suspended sentences+." Kyodo News.[dead link] 26. ^ "‘N’ FORMATION Archived October 14, 2008, at the Wayback Machine." Official Magazine of the New Zealand Air Line Pilots' Association. Issue 7. March 2006. Retrieved on December 11, 2009. 27. ^ "State to pay for '01 JAL near miss Archived February 23, 2009, at the Wayback Machine." The Japan Times. Saturday April 1, 2006. Retrieved on December 11, 2009. 28. ^ "Archived copy" (PDF). Archived from the original (PDF) on 2013-02-06. Retrieved 2014-07-09.CS1 maint: archived copy as title (link) 29. ^ "Air traffic controllers' guilty verdicts final". The Japan Times. December 9, 2010. 30. ^ Barrett, Mathew; Griffiths, Alan; McNab, David; et. all (2011). Prince, Stephen; Gilbert, Roy (eds.). Aircrash Confidential (TV Documentary) (Flying Blind ed.). Discovery Channel: MMXI World Media Rights Limited; WMR Productions; IMG Entertainment. ## External links[edit] * Aircraft and Railway Accidents Investigation Commission * Aircraft Accident Investigation Report (Archive) * (in Japanese) Aircraft Accident Investigation Report (Archive) * Ministry of Land, Infrastructure and Transport * "日本航空９０７便事故に係る書類送検に関する航空局長コメント." May 7, 2003 (15th year of Heisei). (Archive) * "日本航空９０７便事故に係る民事調停成立に関する航空局長コメントについて." March 31, 2006 (18th year of Heisei) (Archive) * Japan Airlines * TOKYO: JANUARY 31, 2001 - FLIGHT JL907 INCIDENT (Archive) * JANUARY 31 NEAR MISS - STATUS REPORT FEBRUARY 1 2001 (Archive) * JL907/JL958 NEAR MISS - CAPTAINS' REPORTS FEB 1 2001 (Archive) * JL907 (Japanese) - Contains a list of passengers injured on Japan Airlines Flight 907 (Japanese) (Archive) * The German Midair – Lessons to be Learned * Close Call For JAL Jets CBS News * Japan Jet in Mid-Air Near-Miss ABC News * A REVIEW OF JAL907/JAL958 NEAR MID-AIR COLLISION. * ９０７便、回避後降下で被害拡大 Mainichi Shimbun * v * t * e Aviation accidents and incidents in Japan * All Nippon Airways Flight 60 (February 1966) * Canadian Pacific Air Lines Flight 402 (March 1966) * BOAC Flight 911 (March 1966) * All Nippon Airways Flight 533 (November 1966) * Toa Domestic Airlines Flight 63 (July 1971) * All Nippon Airways Flight 58 (July 1971) * Japan Airlines Flight 115 (June 1978) * Japan Airlines Flight 350 (February 1982) * Japan Airlines Flight 123 (August 1985) * Japan Air System Flight 451 (April 1993) * China Airlines Flight 140 (April 1994) * Philippine Airlines Flight 434 (December 1994) * Garuda Indonesia Flight 865 (June 1996) * All Nippon Airways Flight 61 (July 1999) * 2001 Japan Airlines mid-air incident (January 2001) * China Airlines Flight 120 (August 2007) * FedEx Express Flight 80 (March 2009) * Asiana Airlines Flight 162 (April 2015) * Korean Air Flight 2708 (May 2016) * v * t * e * ← 2000 * Aviation accidents and incidents in 2001 (2001) * 2002 → * Jan 23 Yemenia Flight 448 * Jan 25 RUTACA Airlines Flight 225 * Jan 27 Omsk An-70 crash * Jan 27 Oklahoma State basketball team crash * Jan 31 Japan Airlines mid-air incident * Feb 7 Iberia Airlines Flight 1456 * Feb 27 Loganair Flight 670A * Mar 3 Thai Airways International Flight 114 * Mar 24 Air Caraïbes Flight 1501 * Mar 29 Avjet Gulfstream III crash * Apr 1 Hainan Island incident * Apr 20 Peru shootdown * May 17 Faraz Qeshm Airlines Yak-40 crash * Jul 4 Vladivostok Air Flight 352 * Aug 24 Air Transat Flight 236 * Aug 25 Marsh Harbour Cessna 402 crash * Aug 29 Binter Mediterráneo Flight 8261 * Sep 11 American Airlines Flight 11 * Sep 11 United Airlines Flight 175 * Sep 11 American Airlines Flight 77 * Sep 11 United Airlines Flight 93 * Sep 11 Delta Air Lines Flight 1989 * Sep 11 Korean Air Flight 85 * Sep 15 TAM Flight 9755 * Sep 17 Grozny Mi-8 crash * Oct 4 Siberia Airlines Flight 1812 * Oct 8 Linate Airport disaster * Nov 12 American Airlines Flight 587 * Nov 12 Fishtail Air Eurocopter AS350 crash * Nov 24 Crossair Flight 3597 * Dec 2 AFRF Flight 9064 * Dec 22 American Airlines Flight 63 * v * t * e JAL Group International * Japan Airlines Regional * Hokkaido Air System * J-Air * Japan Air Commuter * Japan Transocean Air * Ryukyu Air Commuter Former * Japan Airlines Domestic * Japan Asia Airways * JAL Express * JALways History JAL accidents and incidents * Flight 2 (1968) * Flight 351 (1970) * Flight 471 (1972) * Flight 472 (1972) * Flight 446 (1972) * Flight 404 (1973) * Flight 8054 (1977) * Flight 472 (1977) * Flight 115 (1978) * Flight 350 (1982) * Flight 123 (1985) * 2001 Japan Airlines mid-air incident Services * JAL destinations People * Kazuo Inamori [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	2001 Japan Airlines mid-air incident	None	25,055	wikipedia	https://en.wikipedia.org/wiki/2001_Japan_Airlines_mid-air_incident	2021-01-18T18:57:18	{"wikidata": ["Q172129"]}
Ensinck and Palmer (1976) and Palmer et al. (1978) studied a kindred in which 9 members had elevated amounts of high molecular weight forms of immunoreactive glucagon. They proposed that the material may be glucagon precursor(s) and that they are elevated because of an inherited defect in either their synthesis or their degradation. Several instances of male-to-male transmission were observed. No phenotypic peculiarities were associated. No further information is available and no similar families have been reported (Ensinck, 1989). The molecular defect may be in the glucagon gene (138030). Lab \- Hyperproglucagonemia Inheritance \- Autosomal dominant ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	HYPERPROGLUCAGONEMIA	c1840388	25,056	omim	https://www.omim.org/entry/145270	2019-09-22T16:39:52	{"mesh": ["C564159"], "omim": ["145270"], "synonyms": ["Alternative titles", "GLUCAGON, LARGE MOLECULAR WEIGHT SPECIES OF"]}
Hemangioma thrombocytopenia syndrome is characterized by profound thrombocytopenia in association with two rare vascular tumors: kaposiform hemangioendotheliomas and tufted angiomas. The profound thrombocytopenia can cause life threatening bleeding and progress to a disseminated coagulopathy in patients with these tumors. The condition typically occurs in early infancy or childhood, although prenatal cases (diagnosed with the aid of ultrasonography), newborn presentations, and rare adult cases have been reported. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Hemangioma thrombocytopenia syndrome	c0221025	25,057	gard	https://rarediseases.info.nih.gov/diseases/70/hemangioma-thrombocytopenia-syndrome	2021-01-18T18:00:08	{"mesh": ["D059885"], "omim": ["141000"], "umls": ["C0221025"], "orphanet": ["2330"], "synonyms": ["Kasabach Merritt syndrome", "Thrombocytopenia-hemangioma syndrome", "Kasabach Merritt phenomenon", "KMP"]}
Condition which affects multiple organs or the whole body "Life-threatening disease" redirects here. This article's lead section may be too short to adequately summarize its key points. Please consider expanding the lead to provide an accessible overview of all important aspects of the article. (April 2018) A systemic disease is one that affects a number of organs and tissues, or affects the body as a whole.[1] ## Contents * 1 Examples * 2 Detection * 3 See also * 4 References ## Examples[edit] * Mastocytosis, including mast cell activation syndrome and eosinophilic esophagitis * Chronic fatigue syndrome * Systemic vasculitis e.g. SLE, PAN * Sarcoidosis – a disease that mainly affects the lungs, brain, joints and eyes, found most often in young African-American women. * Hypothyroidism – where the thyroid gland produces too little thyroid hormones. * Diabetes mellitus – an imbalance in blood glucose (sugar) levels. * Fibromyalgia * Adrenal insufficiency – where the adrenal glands don't produce enough steroid hormones * Coeliac disease – an autoimmune disease triggered by gluten consumption, which may involve several organs and cause a variety of symptoms, or be completely asymptomatic.[2] * Ulcerative colitis – an inflammatory bowel disease * Crohn's disease – an inflammatory bowel disease * Hypertension (high blood pressure) * Metabolic syndrome * AIDS – a disease caused by a virus that cripples the body's immune defenses. * Graves' disease – a thyroid disorder, most often in women, which can cause a goiter (swelling in the front part of the neck) and protruding eyes. * Systemic lupus erythematosus – a connective tissue disorder involving mainly the skin, joints and kidneys. * Rheumatoid arthritis – an inflammatory disease which mainly attacks the joints. But can also affect a person's skin, eyes, lungs and mouth. * Atherosclerosis – a hardening of the arteries * Sickle cell disease – an inherited blood disorder that can block circulation throughout the body, primarily affecting people of sub-Saharan origin. * Myasthenia gravis * Systemic Sclerosis * Sinusitis ## Detection[edit] Getting a regular eye exam may play a role in identifying the signs of some systemic diseases.[3] "The eye is composed of many different types of tissue. This unique feature makes the eye susceptible to a wide variety of diseases as well as provides insights into many body systems. Almost any part of the eye can give important clues to the diagnosis of systemic diseases. Signs of a systemic disease may be evident on the outer surface of the eye (eyelids, conjunctiva and cornea), middle of the eye and at the back of the eye (retina)."[4] Since 500 B.C., some researchers have believed that the physical condition of the fingernails and toenails can indicate various systemic diseases. Careful examination of the fingernails and toenails may provide clues to underlying systemic diseases[citation needed], since some diseases have been found to cause disruptions in the nail growth process. The nail plate is the hard keratin cover of the nail. The nail plate is generated by the nail matrix located just under the cuticle. As the nail grows, the area closest to becoming exposed to the outside world (distal) produces the deeper layers of the nail plate, while the part of the nail matrix deeper inside the finger (proximal) makes the superficial layers. Any disruption in this growth process can lead to an alteration in the shape and texture. For example, pitting looks like depressions in the hard part of the nail. Pitting is to be associated with psoriasis, affecting 10% - 50% of patients with that disorder. [5] Pitting also may be caused by a variety of systemic diseases, including reactive arthritis and other connective tissue disorders, sarcoidosis, pemphigus, alopecia areata, and incontinentia pigmenti.[6] Because pitting is caused by defective layering of the superficial nail plate by the proximal nail matrix, any localized dermatitis (e.g., atopic dermatitis or chemical dermatitis) that disrupts orderly growth in that area also can cause pitting.[7] ## See also[edit] * Disease * Disseminated disease * Fred Siguier * List of systemic diseases with ocular manifestations * Localized disease * Marfan syndrome * Systemic autoimmune diseases * Systemic inflammation * Oral manifestations of systemic disease ## References[edit] 1. ^ Dorland's Illustrated Medical Dictionary,28th edition (Harcourt Brace & Company). Page 489,1653 2. ^ Lebwohl B, Ludvigsson JF, Green PH (Oct 2015). "Celiac disease and non-celiac gluten sensitivity". BMJ (Review). 351: 4347. doi:10.1136/bmj.h4347. PMC 4596973. PMID 26438584. 3. ^ "Your Eyes Could Be the Windows to Your Health". American Academy of Ophthalmology. Retrieved 4 October 2020. 4. ^ "The Eye in Systemic Disease" (University of Illinois at Chicago: 2008), Available at: http://www.uic.edu/com/eye/LearningAboutVision/EyeFacts/SystemicDisease.shtml, Accessed 20 August 2009. 5. ^ Mayeaux EJ Jr. Nail disorders. Prim Care 2000;27: 333-51. 6. ^ Daniel CR 3d, Sams WM Jr, Scher RK. Nails in systemic disease. Dermatol Clin 1985;3:465-83. 7. ^ Eds. ROBERT S. FAWCETT, M.D., M.S., SEAN LINFORD, M.D., and DANIEL L. STULBERG, M.D., Nail Abnormalities: Clues to Systemic Disease (American Family Physician, March 15, 2004), Available at http://www.aafp.org/afp/20040315/1417.html, Accessed 20 August 2009. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Systemic disease	c0442893	25,058	wikipedia	https://en.wikipedia.org/wiki/Systemic_disease	2021-01-18T18:45:34	{"umls": ["C0442893"], "orphanet": ["182222"], "wikidata": ["Q1414805"]}
A number sign (#) is used with this entry because spinal muscular atrophy type I (SMA1) is caused by mutation or deletion in the telomeric copy of the SMN gene, known as SMN1 (600354), on chromosome 5q13. Changes in expression of the centromeric copy of SMN, SMN2 (601627), are known to modify the phenotype. Description Spinal muscular atrophy refers to a group of autosomal recessive neuromuscular disorders characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy (summary by Wirth, 2000). Four types of SMA are recognized depending on the age of onset, the maximum muscular activity achieved, and survivorship: type I, severe infantile acute SMA, or Werdnig-Hoffman disease; type II (253550), or infantile chronic SMA; type III (253400), juvenile SMA, or Wohlfart-Kugelberg-Welander disease; and type IV (271150), or adult-onset SMA. All types are caused by recessive mutations in the SMN1 gene. Lunn and Wang (2008) provided a detailed review of clinical features, molecular pathogenesis, and therapeutic strategies for SMA. Clinical Features Many groups observed the occurrence of different SMA subtypes within the same family, suggesting different manifestations of a single disease entity. Ghetti et al. (1971) reported that in many families 'malignant' Werdnig-Hoffmann disease coexisted with the Werdnig-Hoffmann disease with a prolonged course, the Wohlfart-Kugelberg-Welander disease with infantile onset, and the Wohlfart-Kugelberg-Welander disease with juvenile onset. Pearn et al. (1973) suggested that both the age of onset and the age of death were important in delineating this disorder and that therefore it should be called the infantile acute form of Werdnig and Hoffmann. Feingold et al. (1977) referred to 'acute' and 'chronic' forms of infantile spinal muscular atrophy. Zerres and Grimm (1983) presented a pedigree in which 2 males died at the age of 13 and 19 months, respectively, of the Werdnig-Hoffmann type of spinal muscular atrophy; a son and daughter of a great-aunt of theirs died at the age of 6 and 3.4 years, respectively, of Werdnig-Hoffmann disease, and a 59-year-old son of a great-uncle of theirs suffered from SMA of the Kugelberg-Welander type, with onset at age 12 years. Thomas and Dubowitz (1994) found a correlation between age of onset and age of death in 2 cohorts of patients with spinal muscular atrophy, consisting of 36 and 70 patients, respectively. In one cohort, the shortest survival was 5 hours, and the longest was 19 months. In the other cohort, the mean age of onset was 1.6 months and the mean age of death was 9.6 months. The data further suggested that patients with onset before 2 months of age have a poor prognosis, with earlier death than those with slightly later onset who still fulfill the diagnostic criteria for type I. Lumaka et al. (2009) reported a boy from central Africa with classic type 1 SMA confirmed by genetic analysis. He presented at birth with axial hypotonia and poor spontaneous movements. By age 5.5 months, he had extreme hypotonia, was unable to hold his head up, and showed psychomotor delay. He had joint laxity, severe proximal muscle weakness, umbilical hernia, atrial septal defect, and recurrent pulmonary infections resulting in death by age 10 months. EMG studies showed evidence for an alpha-motor neuron defect. An older brother who died at 10 months was reportedly similarly affected. Lumaka et al. (2009) noted that this was the first documented report of SMA type 1 in central Africa. ### Pathologic Findings Muscle biopsies of infantile spinal muscular atrophy demonstrate large numbers of round atrophic fibers and clumps of hypertrophic fibers that are type 1 by the ATPase reaction. Soubrouillard et al. (1995) performed immunohistochemical analyses of biopsied skeletal muscle from 23 cases of infantile SMA to determine the expression of developmentally regulated cytoskeletal components, including desmin (125660), NCAM (116930), vimentin (193060), and embryonic and fetal forms of the myosin heavy chain. Strong NCAM and developmental myosin heavy chain expression was present in atrophic fibers. Other Features By analysis of a questionnaire-based retrospective study of 65 patients with SMA type 1, Rudnik-Schoneborn et al. (2008) concluded that congenital heart defects may result from severe SMN deficiency. Among these patients, 4 (6%) had 1 copy of SMN2, 56 (86%) had 2 copies, and 5 (8%) had 3 copies. Three (75%) of the 4 patients with a single SMN2 copy had congenital SMA with atrial or ventricular septal defects. Six of the 56 patients with 2 copies of SMN2 showed minor cardiac anomalies that resolved spontaneously, including a patent foramen ovale (PFO) in 4 infants, associated with a hypertrophic septum in 1, a patent ductus arteriosus (PDA) in 1 patient, and a PDA combined with a PFO in another patient. A small apical ventricular septal defect along with PDA was seen in 1 patient with classic SMA I who died at 11 months. She was the child of consanguineous parents who had lost 4 other children due to alleged sudden infant death syndrome. No cardiac malformation was documented in the 5 patients with 3 SMN2 copies. In a literature review, Rudnik-Schoneborn et al. (2008) noted that most reported SMA patients with heart defects had a severe disease course, prenatal or congenital onset, congenital contractures, respiratory distress from birth, and a very short life span, most likely associated with only 1 SMN2 copy. Ebert et al. (2009) reported the generation of induced pluripotent stem cells from skin fibroblast samples taken from a child with spinal muscular atrophy type 1. These cells expanded robustly in culture, maintained the disease genotype, and generated motor neurons that showed selective deficits compared to those derived from the child's unaffected mother. Ebert et al. (2009) stated that this was the first study to show that human induced pluripotent stem cells can be used to model the specific pathology seen in a genetically inherited disease. Ebert et al. (2009) suggested that since animal models for SMA1 are nonviable, the generation of these pluripotent stem cells would allow more detailed studies of the pathophysiology of SMA1 in the motor neuron. Inheritance Brandt (1949) reported a large study of familial infantile progressive muscular atrophy involving 112 cases in 70 families. Segregation analysis yielded results consistent with autosomal recessive inheritance. Almost 6% of the parents were consanguineous, a value 8 times that in controls. Marquardt et al. (1962), among others, described the disorder in twins. Hogenhuis et al. (1967) reported studies of a Chinese family in which 4 of 8 sibs succumbed to Werdnig-Hoffmann disease. Diagnosis See 600354 for details on the molecular diagnosis of SMA. ### Prenatal Diagnosis Daniels et al. (1992) and Melki et al. (1992) demonstrated the feasibility of prenatal diagnosis of SMA by the linkage principle. Wirth et al. (1995) presented their experience with 109 prenatal diagnoses performed in 91 families at risk of SMA by use of polymorphic microsatellites in the region 5q11.2-q13.3. Of the 109 prenatal diagnoses performed, 29 fetuses were diagnosed to be at more than 99% risk of developing the disease, while in 7 additional pregnancies no exact prediction could be made due to a recombination event in 1 parental haplotype. Pathogenesis Oprea et al. (2008) discovered that unaffected SMN1-deleted females exhibit significantly higher expression of plastin-3 (PLS3; 300131) than their SMA-affected counterparts. The authors demonstrated that PLS3 is important for axonogenesis through increasing the F-actin level. Overexpression of PLS3 rescued the axon length and outgrowth defects associated with SMN downregulation in motor neurons of SMA mouse embryos and in zebrafish. Oprea et al. (2008) concluded that defects in axonogenesis are the major cause of SMA, thereby opening new therapeutic options for SMA and similar neuromuscular diseases. Wen et al. (2010) described a potential link between stathmin (STMN1; 151442) and microtubule defects in SMA. Stathmin was identified by screening Smn-knockdown NSC34 cells through proteomics analysis. Stathmin was aberrantly upregulated in vitro and in vivo, leading to a decreased level of polymerized tubulin, which was correlated with disease severity. Reduced microtubule densities and beta-3-tubulin (TUBB3; 602661) levels in distal axons of affected SMA-like mice and an impaired microtubule network in Smn-deficient cells were observed, suggesting an involvement of stathmin in those microtubule defects. Furthermore, knockdown of stathmin restored the microtubule network defects of Smn-deficient cells, promoted axon outgrowth, and reduced the defect in mitochondria transport in SMA-like motor neurons. The authors concluded that aberrant stathmin levels may play a detrimental role in SMA. Kye et al. (2014) found that expression of microRNA-183 (MIR183; 611608), but not its primary transcript, was increased in Smn-knockdown rat primary neurons, concomitant with impaired axonal growth, impaired local translation of Mtor (601231) in neurites, and reduced Mtor pathway-dependent neurite protein synthesis. Mir183 was also elevated in SMA model mice and in SMA patient-derived fibroblasts. Codepletion of Mir183 and Smn in rat neurons rescued the axonal phenotype and increased Mtor expression in neurites. Kye et al. (2014) identified an Mir183-binding site in the 3-prime UTR of the Mtor transcript, and Mir183 bound directly to this site and inhibited Mtor translation. Inhibition of Mir183 in vivo partly alleviated the disease phenotype in SMA model mice. Kye et al. (2014) concluded that axonal MIR183 and the MTOR pathway contribute to SMA pathology. Clinical Management Chang et al. (2001) reported results suggesting that sodium butyrate may be helpful in the treatment of SMA. They found that this agent increased the amount of exon 7-containing SMN protein in lymphoid cell lines from SMA patients by changing the alternative splicing pattern of exon 7 in the SMN2 gene. Oral administration of sodium butyrate to intercrosses of heterozygous pregnant knockout-transgenic SMA-like mice decreased the birth rate of severe types of SMA-like mice, and SMA symptoms were ameliorated for all 3 types of SMA-like mice. Brichta et al. (2003) showed that in fibroblast cultures derived from SMA patients treated with therapeutic doses of valproic acid (VPA), the level of full-length SMN2 mRNA/protein increased 2- to 4-fold. This upregulation of SMN was most likely attributable to increased levels of HTRA2-beta-1 (see 606441) as well as to SMN gene transcription activation. VPA was also able to increase SMN protein levels through transcription activation in organotypic hippocampal rat brain slices. Additionally, valproic acid increased the expression of other serine-arginine (SR) family proteins, which may have important implications for other disorders affected by alternative splicing. In a study of valproic acid (VPA) treatment in 10 SMA carriers and 20 patients with SMA1, SMA2, or SMA3, Brichta et al. (2006) found that VPA increased peripheral blood full-length SMN mRNA and protein levels in 7 carriers, increased full-length SMN2 mRNA in 7 patients, and left full-length SMN2 mRNA levels unchanged or decreased in 13 patients. The effect on protein levels in carriers was more pronounced than on mRNA levels, and the variability in augmentation among carriers and patients suggested to the authors that valproic acid interferes with transcription of genes encoding translation factors or regulates translation or SMN protein stability. In fibroblast cultures from patients with SMA I, SMA II, or SMA III, Andreassi et al. (2004) found a significant increase in SMN2 gene expression (increase in SMN2 transcripts of 50 to 160% in SMA1, and of 80 to 400% in SMA2 and SMA3) and a more moderate increase in SMN protein expression in response to treatment with 4-phenylbutyrate (PBA). PBA treatment also resulted in an increase in the number of SMN-containing nuclear structures (GEMS). The authors suggested a potential use for PBA in treatment of various types of SMA. Grzeschik et al. (2005) reported that cultured lymphocytes from patients with SMA showed increased production of the full-length SMN mRNA and protein in response to treatment with hydroxyurea. The findings suggested that hydroxyurea promoted inclusion of exon 7 during SMN2 transcription. In a review of questionnaire-based data on 143 SMA patients, Oskoui et al. (2007) found that patients born from 1995 to 2006 had a 70% reduction in the risk of death compared to patients born from 1980 to 1994. However, when controlling for demographic and clinical care variables, the association was no longer significant. Treatment with ventilation for more than 16 hours per day, use of a mechanical insufflation-exsufflation device, and gastrostomy tube feedings showed a significant effect in reducing the risk of death. An amino acid diet had no significant effect on survival. Oskoui et al. (2007) concluded that the increased use of specific proactive management tools has been successful in enhancing survival of patients with SMA. Angelozzi et al. (2008) found that salbutamol increased full-length SMN2 mRNA transcript levels in fibroblasts derived from patients with SMA I, II, and III. The maximum increase (over 200%) was observed after 30 to 60 minutes. This rapid rise correlated with decreased levels of SMN2 with deletion of exon 7. Salbutamol treatment also resulted in increased SMN protein levels and nuclear gems. Yuo et al. (2008) found that treatment of SMA lymphoid cell lines with an Na+/H+ exchange inhibitor resulted in increased expression of SMN2 mRNA with exon 7 and increased SMN protein production in SMA cells. The underlying mechanism appeared to be upregulation of the splicing factor SRp20 (603364) in the nucleus. The findings were consistent with an effect of cellular pH on SMN splicing. Ebert et al. (2009) reported the generation of induced pluripotent stem cells from skin fibroblast samples taken from a child with spinal muscular atrophy type 1. These cells expanded robustly in culture, maintained the disease genotype, and generated motor neurons that showed selective deficits compared to those derived from the child's unaffected mother. Ebert et al. (2009) stated that this was the first study to show that human induced pluripotent stem cells can be used to model the specific pathology seen in a genetically inherited disease. Ebert et al. (2009) suggested that since animal models for SMA1 are nonviable, the generation of these pluripotent stem cells would allow more detailed studies of the pathophysiology of SMA1 in the motor neuron. Through chemical screening and optimization, Naryshkin et al. (2014) identified orally available small molecules that shift the balance of SMN2 splicing toward the production of full-length SMN2 mRNA with high selectivity. Administration of these compounds to delta-7 mice, a model of severe SMA, led to an increase in SMN protein levels, improvement of motor function, and protection of the neuromuscular circuit. These compounds also extended the life span of the mice. Mapping By homozygosity testing of 4 consanguineous families with SMA type I, Gilliam et al. (1990) linked the disorder to chromosome 5q11.2-q13.3, the same region to which the more chronic forms SMA II and SMA III had been mapped. Melki et al. (1990) independently demonstrated that SMA type I, like types II and III, was linked to markers at chromosome 5q12-q14. By in situ hybridization of 2 markers closely flanking the SMA I gene, Mattei et al. (1991) refined the assignment to 5q12-q13.3. Daniels et al. (1992) used in situ hybridization to refine the mapping of SMA I to 5q12.2-q13 near marker D5S6. Brzustowicz et al. (1992) identified 2 flanking loci, MAP1B (157129) and D5S6, which are separated by an interval of approximately 2 cM. Wirth et al. (1993) narrowed the assignment to a region of about 4 cM and defined a new proximal genetic border by the locus D5S125. The closest marker on the distal side of SMA was found to be MAP1B, which has its 5-prime end directed toward the centromere. Lien et al. (1991) used a polyclonal antiserum directed against the C-terminal domain of dystrophin (300377) to isolate a cDNA encoding an antigenically cross-reactive protein. Physical mapping of this gene placed it at 5q13 in close proximity to the SMA locus. A genetic linkage analysis of SMA families using a dinucleotide repeat polymorphism related to the dystrophin-like gene showed tight linkage to SMA mutations. The brain-specific expression of the gene likewise suggested possible association with SMA. By a combination of genetic and physical mapping, Melki et al. (1994) constructed a yeast artificial chromosome (YAC) contig of the 5q13 region spanning the SMN disease locus and showing the presence of low copy repeats. Analysis of allele segregation at the closest genetic loci in 201 SMA families demonstrated inherited and de novo deletions in 9 unrelated SMA patients. Moreover, deletions were strongly suggested in at least 18% of SMA type I patients by the observation of marked deficiency of heterozygosity for the loci studied. The results indicated that deletion events were statistically associated with the severe form of spinal muscular atrophy. Thompson et al. (1995) identified several coding sequences unique to the SMA region. A genomic fragment detected by 1 cDNA was homozygously deleted in 17 of 29 (58%) type I SMA patients. Only 2 of 235 unaffected controls showed the deletion, and both were carriers of the disease. These data suggested that deletion of at least part of this novel gene is directly related to the phenotype of SMA. Molecular Genetics Biros and Forrest (1999), Wirth (2000), and Ogino and Wilson (2004) provided reviews of the complex molecular basis of SMA. SMN1 and SMN2 lie within the telomeric and centromeric halves, respectively, of a large inverted repeat on chromosome 5q. The coding sequence of SMN2 differs from that of SMN1 by a single nucleotide in exon 7 (840C-T), which results in decreased transcription and deficiency of the normal stable SMN protein. Approximately 94% of individuals with SMA lack both copies of SMN1 exon 7, resulting in substantial loss of the protein. Loss of exon 7 can result from deletion or the 840C-T change, in which SMN1 is essentially converted to SMN2 (gene conversion) (Lorson et al., 1999). Loss of SMN1 can also occur by other mechanisms, such as large deletions or point mutations. Most of the SMN protein is derived from the SMN1 gene; however, the SMN2 gene can contribute a small amount of SMN protein, thus modifying the genotype. For a detailed discussion of the molecular genetics of SMA, see 600354. Lefebvre et al. (1995) identified the SMN gene, which they termed 'survival motor neuron,' within the SMA candidate region on chromosome 5q13, and demonstrated deletion or disruption of the gene in 226 of 229 patients with SMA. In a separate publication accompanying that by Lefebvre et al. (1995), Roy et al. (1995) identified a different gene on chromosome 5q13.1, neuronal apoptosis inhibitory protein (NAIP; 600355). They found that the first 2 coding exons of this gene were deleted in approximately 67% of type I SMA chromosomes compared with 2% of non-SMA chromosomes, and reverse transcriptase-PCR analysis revealed internally deleted and mutated forms of the NAIP transcript in type I SMA individuals and not in unaffected individuals. Roy et al. (1995) suggested that mutations in the NAIP locus resulted in a failure of a normally occurring inhibition of motor neuron apoptosis that occurs during development, thus contributing to the SMA phenotype. In a discussion of these seemingly discordant findings, Lewin (1995) suggested that a mutation in either of the 2 genes could result in SMA or that a mutation in both genes was necessary for the disease. Gilliam (1995) discussed the evidence that either the NAIP gene or the SMN gene, or perhaps both, are involved in the causation of SMA. Matthijs et al. (1996) identified homozygous deletion of exon 7 of the SMN1 gene in 34 of 38 patients with SMA. Of these 34 patients, the deletion was associated with homozygous deletion of exon 8 in 31 patients and with heterozygous deletion of exon 8 in 2 patients; both copies of exon 8 were present in 1 patient. In 1 family, a normal father of the proband had only 1 copy of the SMN gene and lacked both copies of the SMN2 gene, showing that a reduction of the total number of SMN genes to a single SMN copy is compatible with normal life. In another family, a de novo deletion of a paternal SMN2 gene was found in a normal sister of a girl with SMA I. Matthijs et al. (1996) suggested that 'this region of chromosome 5q shows some special characteristics which should lead to caution' in the molecular diagnosis of SMA I. Deletions of the SMN gene were not found in 4 of the patients with SMA I. Hahnen et al. (1996) reported molecular analysis of 42 SMA patients who carried homozygous deletions of exon 7 but not of exon 8 in the SMN1 gene. Additional homozygous deletions of exon 8 in the SMN2 gene were found in 2 of the patients. By a simple PCR test, Hahnen et al. (1996) demonstrated the existence of hybrid SMN genes (i.e., genes composed of both the centromeric SMN2 and the telomeric SMN1). They reported a high frequency of hybrid SMN genes in SMA patients with Czech or Polish background. Hahnen et al. (1996) identified a single haplotype for half of the hybrid genes analyzed, suggesting that in these cases the SMA chromosomes shared a common origin. Alias et al. (2009) found homozygous absence of SMN1 exons 7 and 8 in 671 (90%) of 745 Spanish SMA patients. Thirty-seven patients (5%) had homozygous absence of exon 7 but not exon 8, due to the presence of hybrid genes. The majority of the remaining 5% of patients had smaller deletions or point mutations. However, only 1 mutant allele was identified in 7 (0.9%) patients. Data stratification by SMA type showed that females had a significantly higher frequency of type I SMA compared to males. ### Modifying Factors Stratigopoulos et al. (2010) evaluated blood levels of PLS3 (300131) mRNA transcripts in 88 patients with SMA, including 29 males under age 11 years, 12 males over age 11, 29 prepubertal girls, and 18 postpubertal girls in an attempt to examine whether PLS3 was a modifier of the phenotype. PLS3 expression was decreased in the older patients of both sexes. However, expression correlated with phenotype only in postpubertal girls: expression was greatest in those with SMA type III, intermediate in those with SMA type II, and lowest in those with SMA type I, and correlated with residual motor function as well as SMN2 copy number. Stratigopoulos et al. (2010) concluded that the PLS3 gene may be an age- and/or puberty-specific and sex-specific modifier of SMA. Genotype/Phenotype Correlations For a detailed discussion of genotype/phenotype correlations in spinal muscular atrophy, see 600354. Burlet et al. (1996) found large-scale deletions involving both the SMN gene and its upstream (C212-C272) and downstream (NAIP) flanking markers in 43% of 106 unrelated SMA patients. However, they noted that smaller rearrangements can still result in disease, since 27% of patients with severe disease lacked only the SMN gene. They also pointed out that deletion of the SMN gene may produce mild disease and referred to an article by Cobben et al. (l995) in which deletions of the SMN gene were found in unaffected sibs of patients with SMA. Burlet et al. (1996) suggested that other genetic mechanisms might be involved in the variable clinical expression of the disease. Using pulsed field gel electrophoresis to map deletions in the SMN gene, Campbell et al. (1997) found that mutations in SMA types II and III, previously classed as deletions, were in fact due to gene-conversion events in which the telomeric SMN1 was replaced by its centromeric counterpart, SMN2. This resulted in a greater number of SMN2 copies in type II and type III patients compared with type I patients and enabled a genotype/phenotype correlation to be made. Campbell et al. (1997) also demonstrated individual DNA-content variations of several hundred kilobases, even in a relatively isolated population from Finland. This explained why no consensus map of this region of 5q had been produced. They suggested that this DNA variation may be due to a 'midisatellite' array, which would promote the observed high deletion and gene conversion rate. Burghes (1997) discussed the significance of the findings of Campbell et al. (1997) and presented a model (Figure 3) of alleles present in the normal population and in severe and mild forms of SMA. Campbell et al. (1997), Burghes (1997) raised the question of whether the centromeric SMN2 gene might be activated to compensate for the deficiency of SMN1 as a therapeutic strategy in SMA. Samilchuk et al. (1996) carried out deletion analysis of the SMN and NAIP genes in 11 cases of type I SMA and 4 cases of type II SMA. The patients were of Kuwaiti origin. They also analyzed samples from 41 healthy relatives of these patients and 44 control individuals of Arabic origin. They found homozygous deletions of exons 7 and 8 of the SMN gene in all SMA patients studied. Exon 5 of the NAIP gene was homozygously absent in all type I SMA patients, but was retained in the type II patients. Among relatives, they identified 1 mother was had homozygous deletion of NAIP. All of the control individuals had normal SMN and NAIP. Samilchuk et al. (1996) concluded that the incidence of NAIP deletion is much higher in the clinically more severe cases (type I SMA) than in the milder forms, and all of the type II SMA patients in their study had at least one copy of the intact NAIP gene. Somerville et al. (1997) presented a compilation of genotypes for the SMN1 and NAIP genes from their own laboratory and those of others as reported in the literature. Bayesian analyses were used to generate probabilities for SMA when deletions were present or absent in SMN1. They found that when the SMN1 exon 7 was deleted, the probability of SMA could reach greater than 98% in some populations, and when SMN1 was present, the probability of SMA was approximately 17 times less than the prior population risk. Deletion of NAIP exon 5, as well as SMN1 exon 7, was associated with a 5-fold increased risk of type I SMA. Case studies were used to illustrate differing disease risks for pre- and postnatal testing, depending on the presence of information about clinical status or molecular results. These analyses demonstrated that deletion screening of candidate genes can be a powerful tool in the diagnosis of SMA. Novelli et al. (1997) investigated the effects of gender on the association between NAIP gene deletion and disease severity in SMA. NAIP deletions were screened in 197 SMA patients lacking SMN; the results obtained were correlated with disease severity in male and female samples separately. No significant relationship between deletion size and clinical phenotype was observed among male patients, whereas in females the absence of NAIP was strongly associated with a severe phenotype (p less than 0.0001). SMA I was found in 75.6% of females and only 52.5% of males lacking NAIP. These results provided a possible molecular explanation for the sex-dependent phenotypic variation observed in SMA patients. Using comparative genomics to screen for modifying factors in SMA among sequences evolutionarily conserved between mouse and human, Scharf et al. (1998) identified a novel transcript, H4F5 (603011), which lay closer to SMN1 than any previously identified gene in the region. They found that a multicopy microsatellite marker that was deleted in more than 90% of type I SMA chromosomes was embedded in an intron of the SMN1 gene, indicating that H4F5 may also be deleted in type I SMA, and thus was a candidate phenotypic modifier for SMA. In comparison with the high rate of H4F5 deletions in type I SMA, Scharf et al. (1998) found that the deletion frequency in type II SMA chromosomes was between that of type I and control chromosomes, whereas the frequency in type III chromosomes was only slightly higher than in controls. Jedrzejowska et al. (2008) reported 3 unrelated families with asymptomatic carriers of a biallelic deletion of the SMN1 gene. In the first family, the biallelic deletion was found in 3 sibs: 2 affected brothers with SMA3 and a 25-year-old asymptomatic sister. All of them had 4 copies of the SMN2 gene. In the second family, 4 sibs were affected, 3 with SMA2 and 1 with SMA3, and each had 3 copies of SMN2. The clinically asymptomatic 47-year-old father had the biallelic deletion and 4 copies of SMN2. In the third family, the biallelic SMN1 deletion was found in a girl affected with SMA1 and in her healthy 53-year-old father who had 5 copies of SMN2. The findings again confirmed that an increased number of SMN2 copies in healthy carriers of the biallelic SMN1 deletion is an important SMA phenotype modifier, but also suggested that other factors play a role in disease modification. Rudnik-Schoneborn et al. (2009) reviewed the clinical features of 66 German patients with SMA type 1 caused by homozygous deletion of the SMN1 gene. Reduced fetal movements were recorded in 33% of pregnancies. Sixteen (24%) patients showed onset of weakness in the first week of life; the overall mean age at death was 9 months. Four (6.1%) patients with 1 SMN2 gene copy had severe SMA type '0' with joint contractures and respiratory distress from birth. All died within a few months of age. Among the 57 (86.3%) patients with 2 SMN2 copies, the mean age at onset was 1.3 months, and the mean age at disease endpoint (death or need for permanent ventilation) was 7.8 months. Among the 5 (7.6%) of patients with 3 SMN2 copies, the mean age at onset was 3.4 months and the mean age at endpoint was 28.9 months (range, 10 to 55 months). Rudnik-Schoneborn et al. (2009) noted that much of the observed clinical variability in SMA type 1 likely depends on the number of SMN2 copies, and suggested that the SMN2 copy number should be considered in clinical trials. Population Genetics Czeizel and Hamula (1989) and Czeizel (1991) estimated the prevalence of Werdnig-Hoffmann disease in Hungary to be 1 per 10,000 live births. The occurrence in sibs was 32%, a figure considered consistent with autosomal recessive inheritance complicated by greater ascertainment of families with more than 1 affected child. From an epidemiologic study of acute and chronic childhood SMA in Poland, Spiegler et al. (1990) cited a frequency of 1.026 cases per 10,000, a gene frequency of 0.01428, and a carrier frequency of 1 in 35. Spiegler et al. (1990) reviewed various other reports on the frequency of SMA. For an 8-year period (1980-1987) in the State of North Dakota, Burd et al. (1991) found an incidence of 1 in 6,720 births (14 in 94,092). In an Italian population, Mostacciuolo et al. (1992) found an overall prevalence at birth for SMA types I, II, and III to be 7.8 in 100,000 live births. Type I alone accounted for 4.1 in 100,000 live births. Assuming that the 3 types are clinical manifestations of allelic mutations, the locus mutation rate would be about 70 x 10(-6) and the frequency of heterozygotes about 1 in 57. Wilmshurst et al. (2002) performed DNA studies in 30 unrelated and racially diverse patients with SMA residing in the Western Cape of South Africa. Four had SMA type I, 16 had type II, and 10 had type III. All patients were found to be homozygous for the loss of either exon 7 or exons 7 and 8 of the SMN1 gene. Thus, all patients from the Western Cape, which included 12 black South Africans, were no different genetically or phenotypically from the internationally recognized form of typical SMA. Zaldivar et al. (2005) found that the incidence of SMA type I in Cuba was 3.53 per 100,000 live births. When the population was classified according to self-reported ethnicity, the incidence was 8 per 100,000 for whites, 0.89 per 100,000 for blacks, and 0.96 per 100,000 for those of mixed ethnicity. Zaldivar et al. (2005) concluded that SMA I may occur less frequently in those of African ancestry. In a detailed review, Lunn and Wang (2008) stated that the incidence of SMA was 1 in 10,000 livebirths and that the carrier frequency was 1 in 50. In a reply, Wilson and Ogino (2008) stated that carrier testing had revealed a carried frequency of 1 in 38, which extrapolates to an incidence of 1 in 6,000 livebirths under Hardy-Weinberg equilibrium. Wilson and Ogino (2008) postulated that the numerical differences could be due to embryonic lethality or clinically atypical SMA. Hendrickson et al. (2009) genotyped more than 1,000 specimens from various ethnic groups using a quantitative real-time PCR assay specific for the 840C-T change in exon 7, which results in loss of SMN1. The observed 1-copy SMN1 carrier rate was 1 in 37 (2.7%) among Caucasians, 1 in 46 (2.2%) among Ashkenazi Jews, 1 in 56 (1.8%) 56 among Asians, 1 in 91 (1.1%) among African Americans, and 1 in 125 (0.8%) among Hispanics. In all groups except African Americans the 2-copy genotype was the most common. However, African American specimens had an unusually high frequency of alleles with multiple copies of SMN1 (27% compared to 3.3-8.1%). The authors noted that alleles with increased numbers of SMN1 copies increase the relative risk of being a carrier due to the inability of many methods to detect the rare SMN1 genotype consisting of 1 allele with zero copies and the other allele with 2 or more copies. Using denaturing high-performance liquid chromatography (DHPLC) as a screening tool to determine SMN copy number, Sheng-Yuan et al. (2010) found a heterozygous deletion of SMN1 exon 7 in 41 (2.39%) of 1,712 cord blood samples from Chinese infants, indicating a carrier state. Thirteen different genotypic groups characterized by SMN1:SMN2 copy number ratio were identified overall. Carrier genotypes were similar among 25 core families with the disorder, with the '1+0' SMN1 genotype accounting for 90.9% of carriers, although 2 of 44 parents had the rare '2+0' genotype. Sheng-Yuan et al. (2010) developed an assay based on reverse dot blot for rapid genotyping of exon 7 deletional SMA. Sheng-Yuan et al. (2010) concluded that the carrier rate of SMA in China is 1 in 42 and that approximately 2,306 newborns are affected each year. Chong et al. (2011) identified a shared haplotype encompassing the SMN1/SMN2 genes in a Hutterite patient from South Dakota and 3 Hutterite patients from Montana. An 8-generation pedigree connected these 4 individuals to their most recent common ancestors, who were a couple born in the 1790s. All 4 patients carried zero copies of SMN1 and 4 copies of SMN2, indicating that the haplotype carrying the deletion of SMN1 also carries 2 copies of SMN2. The carrier frequency for this haplotype was 12.9% in South Dakota Hutterites. The phenotypic expression of this phenotype was relatively mild, and 1 asymptomatic homozygous adult was identified. Chong et al. (2011) identified a 26-SNP haplotype that could be used for screening in this population. Among 23,127 ethnically diverse individuals screened for SMA1 carrier status, Lazarin et al. (2013) identified 405 carriers (1.8%), for an estimated carrier frequency of approximately 1 in 57. Fifteen 'carrier couples' were identified. History Becker (1964) suggested an allelic model for the clinically distinct subtypes of SMA: 3 or more normal alleles (a, a', a'') in addition to the pathologic gene a(+). The genotype a'a(+) was thought to lead to Kugelberg-Welander phenotype and the a''a(+) genotype to the Werdnig-Hoffmann phenotype. Bouwsma and Leschot (1986) extended the allele hypothesis of Becker. They presented clinical and genetic findings in 18 patients from 7 pedigrees showing an unusual genetic pattern not consistent with simple autosomal recessive inheritance. In 6 of the 7 pedigrees, different types of SMA were present. However, Muller et al. (1992) presented evidence rejecting the Becker hypothesis. In a sample of 4 sibships in which both SMA type II and SMA type III occurred, the segregation of linked markers indicated that the same allele was involved. The finding suggested that other factors, genetic or environmental, must determine disease severity in SMA. Kleyn et al. (1991) excluded both the HEXB locus (606873) and the GM2-activator protein locus (GM2A; 613109), both of which are located on chromosome 5, as the site of the mutation in SMA. Recombination between HEXB and SMA eliminated this enzyme as a candidate site. Furthermore, the gene encoding the activator protein was found to map distal to the SMA I locus (Heng et al., 1993). Animal Model ### Exclusion of the Wobbler Mouse and a Canine Model Kaupmann et al. (1992) mapped the 'wobbler' locus (wr) (see 614633) to proximal mouse chromosome 11. The wobbler mouse (genotype wr/wr) shows motoneuron disease and gonadal dysfunction. Kaupmann et al. (1992) stated that the wobbler was an unlikely model for human SMA because it shows also a striking spermiogenesis defect which has not been reported for male SMA patients who have reached adolescence. Des Portes et al. (1994) also mapped the mouse 'wobbler' mutation to mouse chromosome 11, about 1 cM from the glutamine synthetase gene (138290); several crossovers excluded glutamine synthetase from being a candidate gene for the wobbler mutation. The murine equivalent of the human 5q region is mainly situated on chromosomes 13 and 11, and the closest published marker for human spinal muscular atrophy, D5S39, was mapped to mouse chromosome 13. Thus, it seemed unlikely that the wobbler mutation and the common human spinal muscular atrophies were genetically identical, despite their similar phenotype. Blazej et al. (1998) concluded that autosomal dominant canine spinal muscular atrophy, which has pathologic and clinical features similar to various forms of human motor neuron disease, was molecularly distinct from human spinal muscular atrophy. They studied the canine SMN gene in affected and unaffected dogs and found no germline mutations in the SMN gene in affected dogs. Analysis of a panel of canine/rodent hybrid cell lines revealed that the SMN gene did not map to the same chromosome in the dog as did the canine spinal muscular atrophy. ### Other Animal Models Hsieh-Li et al. (2000) produced mouse lines deficient for mouse Smn and transgenic mouse lines that expressed human SMN2 (601627). Smn -/- mice died during the periimplantation stage. In contrast, transgenic mice harboring SMN2 in the Smn -/- background showed pathologic changes in the spinal cord and skeletal muscles similar to those of SMA patients. The severity of the pathologic changes in these mice correlated with the amount of SMN protein that contained the region encoded by exon 7. The results demonstrated that SMN2 can partially compensate for lack of SMN1. The variable phenotypes of Smn -/- SMN2 mice reflected those seen in SMA patients, thus providing a mouse model for that disease. Frugier et al. (2000) used the Cre/loxP recombination system and a neuron-specific promoter to generate transgenic mice with selective expression in neural tissue of an SMN construct missing exon 7. Unlike mice missing SMN exon 7 in all tissues (an embryonic lethal phenotype), those with a neuron-specific defect displayed a severe motor deficit with tremors. The mutated SMN protein lacked the normal C terminus and was dramatically reduced in motor neuron nuclei. Histologic analysis revealed a lack of GEMS (gemini of coiled bodies, which are normal nuclear structures) and the presence of large aggregates of coilin, a coiled body-specific protein (600272). The authors concluded that the lack of nuclear targeting of SMN is the biochemical defect in SMA, which leads to muscle denervation of neurogenic origin. Studying Brown-Swiss cattle, Medugorac et al. (2003) mapped the bovine spinal muscular atrophy locus to chromosome 24. Before performing a genomewide linkage analysis, they investigated 2 candidate chromosome segments: the proximal part of bovine chromosome 20 and the complete bovine chromosome 29. These regions are orthologous to human chromosome segments responsible for SMA1 and SMA with respiratory distress (SMARD1; 604320), respectively. No abnormalities were found in these regions. The linkage region on chromosome 24 contains the homolog of the BCL2 gene (151430) on human chromosome 18q. Medugorac et al. (2003) suggested that the gene encoding the apoptosis-inhibiting protein BCL2 is a promising candidate for bovine SMA and that the disorder in Brown-Swiss cattle offers an attractive animal model for a better understanding of human SMA and for a probable antiapoptotic synergy of SMN-BCL2 aggregates in mammals. Chan et al. (2003) isolated a Drosophila smn mutant with point mutations in the smn gene similar to those found in SMA patients. Zygotic smn mutant animals showed abnormal motor behavior; smn gene activity was required in both neurons and muscle to alleviate this phenotype. Excitatory postsynaptic currents were reduced while synaptic motor neuron boutons were disorganized in mutants, indicating defects at the neuromuscular junction. Clustering of a neurotransmitter receptor subunit in the muscle at the neuromuscular junction was also severely reduced. In a mouse model of SMA, Kariya et al. (2008) demonstrated that the earliest structural defects of the disorder appeared in the distal muscles and involved the neuromuscular synapse even before the appearance of overt symptoms. Insufficient SMN protein arrested the postnatal development of the neuromuscular junction (NMJ), impairing the maturation of postsynaptic acetylcholine receptor (AChR) clusters. Presynaptic defects at the distal ends of alpha-motor neurons included poor terminal arborization, intermediate filament aggregates, and misplaced synaptic vesicles. These defects were reflected in functional deficits at the NMJ characterized by intermittent neurotransmission failures. Kariya et al. (2008) suggested that SMA might best be described as a NMJ synaptopathy. In severe SMA mice (Smn -/-;SMN2 +/+) Gavrilina et al. (2008) found that transgenic embryonic expression of full-length SMN under the prion (176640) promoter in brain and spinal cord neurons rescued the phenotype. Mice homozygous for the transgene survived for an average of 210 days, compared to 4.6 days in control SMA mice, and lumbar motor neuron root counts in the transgenic mice were normal. High levels of SMN in neurons were observed at embryonic day 15. In contrast, transgenic expression of SMN solely in skeletal muscle using the human skeletal actin promoter resulted in no improvement of the SMA phenotype or extension of survival in SMA mice. However, 1 transgenic strain with high SMN expression in muscle and low SMN expression in brain showed increased survival to 160 days, indicating that even mild neuronal SMN expression can affect the phenotype. Gavrilina et al. (2008) concluded that expression of full-length SMN in neurons can correct the severe SMA phenotype in mice, whereas high SMN levels in mature skeletal muscle alone has no impact. Murray et al. (2010) investigated the presymptomatic development of neuromuscular connectivity in differentially vulnerable motor neuron populations in Smn -/-;SMN2 +/+ mice. Reduced Smn levels had no detectable effect on morphologic correlates of presymptomatic development in either vulnerable or stable motor units, indicating that abnormal presymptomatic developmental processes were unlikely to be a prerequisite for subsequent pathologic changes to occur in vivo. Microarray analyses of spinal cord from 2 different severe SMA mouse models demonstrated that only minimal changes in gene expression were present in presymptomatic mice. In contrast, microarray analysis of late-symptomatic spinal cord revealed widespread changes in gene expression, implicating extracellular matrix integrity, growth factor signaling, and myelination pathways in SMA pathogenesis. Murray et al. (2010) suggested that reduced Smn levels induce SMA pathology by instigating rapidly progressive neurodegenerative pathways in lower motor neurons around the time of disease onset, rather than by modulating presymptomatic neurodevelopmental pathways. Wishart et al. (2010) showed that reduced levels of Smn led to impaired perinatal brain development in a mouse model of severe SMA. Regionally selective changes in brain morphology were apparent in areas normally associated with higher Smn levels in the healthy postnatal brain, including the hippocampus, and were associated with decreased cell density, reduced cell proliferation, and impaired hippocampal neurogenesis. A comparative proteomics analysis of the hippocampus from SMA and wildtype littermate mice revealed widespread modifications in expression levels of proteins regulating cellular proliferation, migration, and development when Smn levels were reduced. Wishart et al. (2010) proposed roles for SMN protein in brain development and maintenance. ### Therapeutic Strategies In SMA-like mouse embryonic fibroblasts and human SMN2-transfected motor neuron cells, Ting et al. (2007) found that sodium vanadate, trichostatin A, and aclarubicin effectively enhanced SMN2 expression by inducing Stat5 (601511) activation. This resulted in enhanced SMN2 promoter activity with an increase in both full-length and deletion exon 7 SMN transcripts in human cells with SMN2. Knockdown of Stat5 expression disrupted the effects of sodium vanadate on SMN2 activation, but did not influence SMN2 splicing, suggesting that Stat5 signaling is involved in SMN2 transcriptional regulation. Constitutive expression of the activated Stat5 mutant Stat5A16 profoundly increased the number of nuclear gems in SMA patient lymphocytes and reduced SMA-like motor neuron axon outgrowth defects. Narver et al. (2008) found that in a transgenic mouse model of SMA (Smn +/-, SMN2 +/+, SMN-delta-7) early treatment with the HDAC (601241) inhibitor, trichostatin A (TSA), plus nutritional support extended median survival by 170%. Treated mice continued to gain weight, maintained stable motor function, and retained intact neuromuscular junctions long after TSA was discontinued. In many cases, ultimate decline of mice appeared to result from vascular necrosis, raising the possibility that vascular dysfunction is part of the clinical spectrum of severe SMA. Narver et al. (2008) concluded that early SMA disease detection and treatment initiation combined with aggressive ancillary care may be integral to the optimization of HDAC inhibitor treatment in human patients. Meyer et al. (2009) created an optimal exon 7 inclusion strategy based on a bifunctional U7 snRNA (RNU7-1; 617876) construct that targets the 3-prime part of exon 7 and carries an ESE sequence that can attract stimulatory splice factors. This construct induced nearly complete exon 7 inclusion of an SMN2-reporter in HeLa cells and of endogenous SMN2 in SMA type I patient fibroblasts. Introduction of the U7-ESE-B construct in a severe mouse model of SMA resulted in a clear suppression of disease-associated symptoms, ranging from normal life span with pronounced SMA symptoms to full weight development, muscular function, and ability of female mice to carry to term and feed a normal-sized litter. Exon 7 inclusion in total spinal RNA increased from 26% to 52%, and SMN protein levels increased, albeit only to levels one-fifth of that seen wildtype mice. Workman et al. (2009) showed that SMN(A111G), an allele capable of snRNP assembly (A111G; 600354.0015), can rescue mice that lacked Smn and contained either 1 or 2 copies of SMN2 (SMA mice). The correction of SMA in these animals was directly correlated with snRNP assembly activity in spinal cord, as was correction of snRNA levels. These data support snRNP assembly as being the critical function affected in SMA and suggests that the levels of snRNPs are critical to motor neurons. Furthermore, SMN(A111G) could not rescue Smn-null mice without SMN2, suggesting that both SMN(A111G) and SMN from SMN2 may undergo intragenic complementation in vivo to function in heteromeric complexes that have greater function than either allele alone. The oligomer composed of limiting full-length SMN and SMN(A111G) had substantial snRNP assembly activity. The SMN(A2G) (A2G; 600354.0002) and SMN(A111G) alleles in vivo did not complement each other, leading to the possibility that these mutations could affect the same function. Mattis et al. (2009) examined the potential therapeutic capabilities of a novel aminoglycoside, TC007. In an intermediate SMA mouse model (Smn -/-; SMN2 +/+; SMN-delta-7), when delivered directly to the central nervous system, TC007 induced SMN in both the brain and spinal cord, significantly increased life span (approximately 30%), and increased ventral horn cell number, consistent with its ability to increase SMN levels in induced pluripotent stem cell-derived human SMA motor neuron cultures. Butchbach et al. (2010) tested a series of C5-quinazoline derivatives for their ability to increase SMN expression in vivo. Oral administration of 3 compounds (D152344, D153249, and D156844) to neonatal SMN-delta-7 mice resulted in a dose-dependent increase in Smn promoter activity in the central nervous system. Oral administration of D156844 significantly increased the mean life span of SMN-delta-7 SMA mice by approximately 20-30% when given prior to motor neuron loss. Bowerman et al. (2010) showed that Smn depletion led to increased activation of RhoA (165390), a major regulator of actin dynamics, in the spinal cord of an intermediate SMA mouse model. Treating these mice with Y-27632, which inhibits ROCK (601702), a direct downstream effector of RhoA, dramatically improved their survival. This life span rescue was independent of Smn expression and was accompanied by an improvement in the maturation of the neuromuscular junctions and an increase in muscle fiber size in the SMA mice. Bowerman et al. (2010) proposed a role for disruption of actin cytoskeletal dynamics to SMA pathogenesis and suggested that RhoA effectors may be viable targets for therapeutic intervention in the disease. Ackermann et al. (2013) found that ubiquitous overexpression of human PLS3 (300131) in mice with a mild SMA phenotype improved motor ability and neuromuscular junction function and moderately increased survival compared with control SMA mice. Expression of PLS3 did not improve the morphology of heart, lung, or intestine, and it did not improve motor ability or survival in mice with a severe SMA phenotype. The authors noted that these findings were consistent with observations in humans showing that PLS3 provides full protection against SMA only in SMN1-deleted individuals with 3 to 4 SMN2 copies, but not in those with 2 SMN2 copies. In mildly affected SMA mice, PLS3 delayed axon pruning until postnatal day 8, which counteracted the poor synaptic activity observed in control SMA mice. F-actin content was increased in presynapses, leading to improved neuromuscular connectivity, restored active zone content of synaptic vesicles, improved organization of the ready releasable vesicle pool, increased endplate and muscle fiber size, and improved neurotransmission. INHERITANCE \- Autosomal recessive CARDIOVASCULAR Heart \- Congenital cardiac malformations have been rarely reported in severe cases \- Ventricular septal defect \- Atrial septal defect RESPIRATORY \- Respiratory failure NEUROLOGIC Central Nervous System \- Muscle weakness, symmetric, proximal (lower limbs more affected than upper limbs) due to motor neuronopathy \- Muscle atrophy \- Affected children are unable to sit without support \- Facial muscle sparing \- Tongue fasciculations/fibrillations \- Normal motor conduction studies (initially) \- EMG shows neurogenic abnormalities \- Areflexia \- Loss of lower alpha-motor neurons in the anterior horn of the spinal cord and lower brainstem PRENATAL MANIFESTATIONS Movement \- Decreased fetal movement MISCELLANEOUS \- Death secondary to respiratory infection or failure before age 2 years \- Onset birth to 6 months \- Incidence 1 in 6,000 to 1 in 8,000 live births \- Approximately 45% of SMA1 patients also are missing both homologs of neuronal apoptosis inhibitory protein (NAIP, 600355 ), which may play a role in modifying disease severity \- Exon 7 of SMN1 is absent in 95.6% of SMA1 patients MOLECULAR BASIS \- Caused by mutation in the survival of motor neuron 1 gene (SMN1, 600354.0001 ) ▲ 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	SPINAL MUSCULAR ATROPHY, TYPE I	c0043116	25,059	omim	https://www.omim.org/entry/253300	2019-09-22T16:24:52	{"doid": ["13137"], "mesh": ["D014897"], "omim": ["253300"], "icd-9": ["335.0"], "icd-10": ["G12.0"], "orphanet": ["70", "83330"], "synonyms": ["Alternative titles", "SMA I", "SMA, INFANTILE ACUTE FORM", "WERDNIG-HOFFMANN DISEASE", "MUSCULAR ATROPHY, INFANTILE", "SMA"], "genereviews": ["NBK1352"]}
## Clinical Features Cantu et al. (1991) described 2 unrelated patients, a 21-year-old male and an 11-year-old female, with a form of osteochondrodysplasia that was later called spondyloepiphyseal dysplasia-brachydactyly and distinctive speech (SED-BDS), Fantasy Island syndrome, or Tattoo dysplasia (Cantu, 1995; Lachman, 2007). Features included dwarfism, peculiar facies with blepharophimosis, upward slanted eyes, abundant eyebrows and eyelashes, harsh voice, and short hands and feet. Radiographically, the patients had brachymetacarpalia, brachymetatarsia, and brachyphalangia of all fingers and toes, shortened and broadened long bones with normal morphology, small pelvis, and shape anomalies of the vertebral bodies. The parents of both patients were nonconsanguineous. Garcia-Cruz et al. (2007) described an affected mother-son pair and an additional patient with features similar to those of the patients reported by Cantu et al. (1991). The proband of the first family was an 18-year-old male who was the second pregnancy of nonconsanguineous parents. He had disproportionate short stature (-3 SD), blepharophimosis, abundant eyebrows and curly eyelashes, upslanted palbebral fissures, broad and depressed nasal bridge, short neck, short thorax with pectus excavatum, abundant axillary, pubic, and body hair, rhizomesoacromelic shortness in all extremities, short hands and feet, and a coarse voice. Radiographs revealed cuboid-shaped vertebral bodies and lack of lumbar lordosis, short and broad tubular bones, brachymetacarpalia and brachymetatarsia, and brachydactyly. His 40-year-mother, described as moderately affected, had short stature (-3.5 SD) and similar facial characteristics. Garcia-Cruz et al. (2007) proposed that SED-BDS is inherited in an autosomal dominant manner since both sexes were affected and parental consanguinity was absent. However, X-linked dominant inheritance could not be excluded. History Historically, the first described patient with this skeletal dysplasia is Herve Villechaize, the actor well known as Tatoo in the U.S. television series 'Fantasy Island' (Lachman, 2007). INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature, disproportionate short limb \- Normal birth length Other \- Growth retardation, progressive HEAD & NECK Face \- Coarse facies \- Round face \- Midface hypoplasia \- Long philtrum Ears \- Small pinnae Eyes \- Blepharophimosis \- Upslanting palpebral fissures \- Curly eyebrows \- Curly eyelashes Nose \- Broad nasal bridge \- Depressed nasal bridge \- Upturned nose Mouth \- Large mouth \- Thick lower lip Neck \- Wide neck \- Short neck RESPIRATORY Lung \- Restrictive lung disease CHEST External Features \- Small thorax Ribs Sternum Clavicles & Scapulae \- Thickened clavicles \- Pectus excavatum SKELETAL \- Spondyloepiphyseal dysplasia \- Mild joint contractures \- Small epiphyses \- Generalized epiphyseal ossification delay Spine \- Lack of lumbar lordosis \- Mild platyspondyly \- Anterior scalloping vertebral bodies \- Cuboid-shaped vertebral bodies Pelvis \- Hypoplastic iliac wings Limbs \- Rhizo-meso-acromelic limb shortening \- Short long bones \- Limited pronation \- Limited supination \- Cubitus valgus Hands \- Short hands \- Brachydactyly \- Short, tapered phalanges \- Single interphalangeal crease of fifth finger \- Short, tapered metacarpals \- Brachymetacarpals \- Small carpals Feet \- Short feet \- Brachydactyly \- Brachymetatarsals SKIN, NAILS, & HAIR Hair \- Abundant thick, curly scalp hair \- Abundant and curly eyelashes \- Abundant and curly eyebrows \- Increased hair on arms and legs \- Low-set nuchal hair VOICE \- High-pitched, coarse voice ▲ 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	SPONDYLOEPIPHYSEAL DYSPLASIA-BRACHYDACTYLY AND DISTINCTIVE SPEECH	c2673649	25,060	omim	https://www.omim.org/entry/611717	2019-09-22T16:02:55	{"mesh": ["C567128"], "omim": ["611717"], "orphanet": ["163654"], "synonyms": ["Alternative titles", "SED-BDS", "FANTASY ISLAND SYNDROME", "TATOO DYSPLASIA"]}
A rare head and neck tumor characterized by a firm infiltrative neoplasm with squamous differentiation, most commonly arising at the vermilion border of the lower lip. Patients present with a usually asymptomatic lesion of variable appearance, such as ulceration, a focus of whitish thickening, a dry atrophic area, or an area of persistent chapping and localized flaking and crusting. Carcinomas of the lower lip tend to progress slowly (as opposed to those of the upper lip). Invasion of adjacent structures, including perineural spread, is typical, with a variable rate of metastasis, depending on the location. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Squamous cell carcinoma of the lip	c1168401	25,061	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=502366	2021-01-23T16:57:23	{"mesh": ["D000077195"], "omim": ["275355"]}
Schofer et al. (1990) described 2 brothers with nephrogenic diabetes insipidus, intracerebral calcifications, defective psychomotor development, dwarfism, and peculiar facial appearance. The disorder had some resemblance to Cockayne syndrome (216400), from which, however, the authors thought it to be distinct. Another sib, a twin of one of the brothers, had the same condition and died at the age of 7 years. The oldest surviving brother was 147 cm tall at the age of 25 years. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	DIABETES INSIPIDUS, NEPHROGENIC, WITH MENTAL RETARDATION AND INTRACEREBRAL CALCIFICATION	c2931070	25,062	omim	https://www.omim.org/entry/221995	2019-09-22T16:28:44	{"mesh": ["C535949"], "omim": ["221995"], "orphanet": ["3145"]}
Genetic condition that predisposes a person to cancer Familial adenomatous polyposis is a cancer syndrome in which there are hundreds to thousands of benign adenomas in the colon. A cancer syndrome, or family cancer syndrome, is a genetic disorder in which inherited genetic mutations in one or more genes predispose the affected individuals to the development of cancers and may also cause the early onset of these cancers. Cancer syndromes often show not only a high lifetime risk of developing cancer, but also the development of multiple independent primary tumors.[1] Many of these syndromes are caused by mutations in tumor suppressor genes, genes that are involved in protecting the cell from turning cancerous. Other genes that may be affected are DNA repair genes, oncogenes and genes involved in the production of blood vessels (angiogenesis).[2] Common examples of inherited cancer syndromes are hereditary breast-ovarian cancer syndrome and hereditary non-polyposis colon cancer (Lynch syndrome).[3][4] ## Contents * 1 Background * 2 Genetics of cancer * 3 Examples * 3.1 Fanconi anemia * 3.2 Familial adenomatous polyposis * 3.3 Hereditary breast and ovarian cancer * 3.4 Hereditary non-polyposis colon cancer * 3.5 Hereditary paraganglioma-pheochromocytoma syndrome * 3.6 Li-Fraumeni syndrome * 3.7 MUTYH-associated polyposis * 3.8 Nevoid basal cell carcinoma syndrome * 3.9 Von Hippel–Lindau disease * 3.10 Xeroderma pigmentosum * 4 DNA repair defects and increased cancer risk * 5 Genetic screening * 6 Preventive actions * 7 Prevalence of genetic mutations in different ethnic groups * 8 References ## Background[edit] Hereditary cancer syndromes underlie 5 to 10% of all cancers and there are over 50 identifiable hereditary forms of cancer.[5] Scientific understanding of cancer susceptibility syndromes is actively expanding: additional syndromes are being found,[6] the underlying biology is becoming clearer, and commercialization of diagnostic genetics methodology is improving clinical access.[citation needed] Given the prevalence of breast and colon cancer, the most widely recognized syndromes include hereditary breast-ovarian cancer syndrome and hereditary non-polyposis colon cancer (Lynch syndrome).[6] Some rare cancers are strongly associated with hereditary cancer predisposition syndromes. Genetic testing should be considered with adrenocortical carcinoma; carcinoid tumors; diffuse gastric cancer; fallopian tube/primary peritoneal cancer; leiomyosarcoma; medullary thyroid cancer; paraganglioma/pheochromocytoma; renal cell carcinoma of chromophobe, hybrid oncocytic, or oncocytoma histology; sebaceous carcinoma; and sex cord tumors with annular tubules.[6] Primary care physicians can identify people who are at risk of heridatary cancer syndrome.[7] ## Genetics of cancer[edit] Example pedigree chart of autosomal dominant inheritance. Many cancer syndromes are inherited in this manner. Less commonly, cancer syndromes are inherited in an autosomal recessive manner. In this example pedigree chart the only person that will have an increased risk of cancer is the homozygous recessive male in the second generation; although there are many carriers of the gene. Two copies of every gene are present in all cells of the body and each one is called an allele. Most cancer syndromes are transmitted in a mendelian autosomal dominant manner. In these cases, only one faulty allele has to be present for an individual to have a predisposition to cancer. Individuals with one normal allele and one faulty allele are known as heterozygous. A heterozygous individual and a person with two normal alleles (homozygous) will have a 50% chance of producing an affected child.[8] The mutation in the inherited gene is known as a germline mutation and a further mutation in the normal allele results in the development of cancer. This is known as Knudson's two-hit hypothesis, where the first hit of the gene is the inherited mutation and the second hit occurs later in life.[2] As only one allele needs to be mutated (as compared to both in so-called "sporadic cancers"), the individual has a higher chance of developing the cancer than the general population.[citation needed] Less often, syndromes may be transmitted as an autosomal recessive trait. Both alleles of a gene must be mutated in autosomal recessive disorders for an individual to have a predisposition to cancer. A person with two recessive alleles is known as homozygous recessive. Both parents must have at least one faulty allele in order for a child to be homozygous recessive. If both parents have one mutant allele and one normal allele (heterozygous) then they have a 25% chance of producing a homozygous recessive child (has predisposition), 50% chance of producing a heterozygous child (carrier of the faulty gene) and 25% chance of produced a child with two normal alleles.[8] Examples of autosomal dominant cancer syndromes are autoimmune lymphoproliferative syndrome (Canale-Smith syndrome), Beckwith–Wiedemann syndrome (although 85% of cases are sporadic),[citation needed] Birt–Hogg–Dubé syndrome, Carney syndrome, familial chordoma, Cowden syndrome, dysplastic nevus syndrome with familial melanoma, familial adenomatous polyposis, hereditary breast–ovarian cancer syndrome, hereditary diffuse gastric cancer (HDGC), Hereditary nonpolyposis colorectal cancer (Lynch syndrome), Howel–Evans syndrome of esophageal cancer with tylosis, juvenile polyposis syndrome, Li–Fraumeni syndrome, multiple endocrine neoplasia type 1/2, multiple osteochondromatosis, neurofibromatosis type 1/2, nevoid basal-cell carcinoma syndrome (Gorlin syndrome), Peutz–Jeghers syndrome, familial prostate cancer, hereditary leiomyomatosis renal cell cancer (LRCC), hereditary papillary renal cell cancer, hereditary paraganglioma-pheochromocytoma syndrome, retinoblastoma, tuberous sclerosis, von Hippel–Lindau disease and Wilm's tumor.[9] Examples of autosomal recessive cancer syndromes are ataxia–telangiectasia, Bloom syndrome, Fanconi anemia, MUTYH-associated polyposis, Rothmund–Thomson syndrome, Werner syndrome and Xeroderma pigmentosum.[9] ## Examples[edit] Although cancer syndromes exhibit an increased risk of cancer, the risk varies. For some of these diseases, cancer is not their primary feature. The discussion here focuses on their association with an increased risk of cancer. This list is far from exhaustive. ### Fanconi anemia[edit] Fanconi anemia is a disorder with a wide clinical spectrum, including: early onset and increased risk of cancer; bone marrow failure; and congenital abnormalities. The most prominent manifestations of this disorder are those related to hematopoeisis (production of blood by the bone marrow); these include aplastic anemia, myelodysplastic syndrome and acute myeloid leukemia. Hepatic tumors and squamous cell carcinomas of the esophagus, oropharynx and uvula are solid tumors commonly linked to FA. Congenital abnormalities include: skeletal anomalies (especially those affecting the hands), cafe au lait spots and hypopigmentation. To date, the genes known to cause FA are: FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ, FANCL, FANCM, FANCN, FANCO, FANCP and BRCA2 (previously known as FANCD1). Inheritance of this syndrome is primarily autosomal recessive, but FANCB can be inherited from the maternal or paternal x-chromosome (x-linked recessive inheritance). The FA pathway is involved in DNA repair when the two strands of DNA are incorrectly joined together (interstrand crosslinks). Many pathways are coordinated by the FA pathway for this including nucleotide excision repair, translesion synthesis and homologous recombination.[10][11][12][13][14] ### Familial adenomatous polyposis[edit] Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome that greatly increases the risk of colorectal cancer. Around 1 in 8000 people will have this disease and it has approximately 100% penetrance. An individual with this disease will have hundreds to thousands of benign adenomas throughout their colon, which will in most cases progress to cancer. Other tumors increased in frequency include; osteomas, adrenal adenomas and carcinomas, thyroid tumors and desmoid tumors. The cause of this disorder is a mutated APC gene, which is involved in β-catenin regulation. Faulty APC causes β-catenin to accumulate in cells and activate transcription factors involved in cell proliferation, migration, differentiation and apoptosis (programmed cell death).[15][16][17] ### Hereditary breast and ovarian cancer[edit] Hereditary breast-ovarian cancer syndrome is an autosomal dominant genetic disorder caused by genetic mutations of the BRCA1 and BRCA2 genes. In women this disorder primarily increases the risk of breast and ovarian cancer, but also increases the risk of fallopian tube carcinoma and papillary serous carcinoma of the peritoneum. In men the risk of prostate cancer is increased. Other cancers that are inconsistently linked to this syndrome are pancreatic cancer, male breast cancer, colorectal cancer and cancers of the uterus and cervix. Genetic mutations account for approximately 7% and 14% of breast and ovarian cancer, respectively, and BRCA1 and BRCA2 account for 80% of these cases. BRCA1 and BRCA2 are both tumor suppressor genes implicated in maintaining and repairing DNA, which in turn leads to genome instability. Mutations in these genes allow further damage to DNA, which can lead to cancer.[18][19] ### Hereditary non-polyposis colon cancer[edit] Hereditary non-polyposis colon cancer, also known as Lynch syndrome, is an autosomal dominant cancer syndrome that increases the risk of colorectal cancer. It is caused by genetic mutations in DNA mismatch repair (MMR) genes, notably MLH1, MSH2, MSH6 and PMS2. In addition to colorectal cancer many other cancers are increased in frequency. These include; endometrial cancer, stomach cancer, ovarian cancer, cancers of the small bowel and pancreatic cancer. Hereditary non-polyposis colon cancer is also associated with an early onset of colorectal cancer. MMR genes are involved in repairing DNA when the bases on each strand of DNA do not match. Defective MMR genes allow continuous insertion and deletion mutations in regions of DNA known as microsatellites. These short repetitive sequences of DNA become unstable, leading to a state of microsatellite instability (MSI). Mutated microsatellites are often found in genes involved in tumor initiation and progression, and MSI can enhance the survival of cells, leading to cancer.[4][20][21][22] Although the majority of Fanconi anemia cases are inherited in an autosomal recessive manner, those caused by FANCB are inherited through x-linked recessive inheritance. This example pedigree chart shows how inheritance of X-linked Fanconi anemia might occur through several generations. ### Hereditary paraganglioma-pheochromocytoma syndrome[edit] Most cases of familial paraganglioma are caused by mutations in the succinate dehydrogenase (succinate:ubiquinone oxidoreductase) subunit genes (SDHD, SDHAF2, SDHC, SDHB). PGL-1 is associated with SDHD mutation, and most PGL-1 individuals with paraganglioma have affected fathers rather than affected mothers. PGL1 and PGL2 are autosomal dominant with imprinting. PGL-4 is associated with SDHB mutation and is associated with a higher risk of pheochromocytoma, as well as renal cell cancer and non-medullary thyroid cancer.[23] ### Li-Fraumeni syndrome[edit] Li-Fraumeni syndrome is an autosomal dominant syndrome primarily caused by mutations in the TP53 gene, which greatly increases the risk of many cancers and is also highly associated with early onset of these cancers. Cancers linked to this disorder include; soft tissue sarcomas (often found in childhood), osteosarcoma, breast cancer, brain cancer, leukaemia and adrenocortical carcinoma. Individuals with Li-Fraumeni syndrome often have multiple independent primary cancers. The reason for the large clinical spectrum of this disorder may be due to other gene mutations that modify the disease. The protein produced by the TP53 gene, p53, is involved in cell cycle arrest, DNA repair and apoptosis. Defective p53 may not be able to properly perform these processes, which may be the reason for tumor formation. Because only 60-80% of individuals with the disorder have detectable mutations in TP53, other mutations in the p53 pathway may be involved in Li-Fraumeni syndrome.[24][25][26][27] ### MUTYH-associated polyposis[edit] MUTYH-associated polyposis shares most of its clinical features with FAP; the difference is that it is an autosomal recessive disorder caused by mutations in the MUTYH DNA repair gene. Tumors with increased risk in this disorder are colorectal cancer, gastric adenomas and duodenal adenomas.[15][28] Micrograph showing keratocystic odontogenic tumour, a common finding in nevoid basal cell carcinoma syndrome. H&E stain. ### Nevoid basal cell carcinoma syndrome[edit] Nevoid basal cell carcinoma syndrome, also known as Gorlin syndrome, is an autosomal dominant cancer syndrome in which the risk of basal cell carcinoma is very high. The disease is characterized by basal cell nevi, jaw keratocysts and skeletal abnormalities. Estimates of nevoid basal cell carcinoma syndrome prevalence varies, but is approximately 1 in 60000. The presence of basal cell carcinoma is much higher in white than black individuals; 80% and 38%, respectively. Odontogenic keratocysts are found in approximately 75% of individuals with the disease and often occur early in life. The most common skeletal abnormalities occur in the head and face, but other areas are often affected such as the rib cage. The causative genetic mutation of this disease occurs in the PTCH gene, and the product of PTCH is a tumor suppressor involved in cell signaling. Although the exact role of this protein in nevoid basal cell carcinoma syndrome is not known, it is involved in the hedgehog signaling pathway, known to control cell growth and development.[29][30] ### Von Hippel–Lindau disease[edit] Von Hippel–Lindau disease is a rare, autosomal dominant genetic condition that predisposes individuals to benign and malignant tumors. The most common tumors in Von Hippel–Lindau disease are central nervous system and retinal hemangioblastomas, clear cell renal carcinomas, pheochromocytomas, pancreatic neuroendocrine tumours, pancreatic cysts, endolymphatic sac tumors and epididymal papillary cystadenomas.[31][32] Von Hippel–Lindau disease results from a mutation in the von Hippel–Lindau tumor suppressor gene on chromosome 3p25.3.[33] ### Xeroderma pigmentosum[edit] Xeroderma pigmentosum is an autosomal recessive disorder characterized by sensitivity to ultra-violet (UV) light, massively increased risk of sunburn and increased risk of skin cancers. The risk of skin cancer is more than 10000 times that of normal individuals and includes many types of skin cancer, including melanoma and non-melanoma skin cancers. Also, sun exposed areas of the tongue, lips and eyes have an increased risk of becoming cancerous. Xeroderma pigmentosum may be associated with other internal cancers and benign tumors.[citation needed] In addition to cancer, some genetic mutations that cause xeroderma pigmentosum are associated with neurodegeneration. Xeroderma pigmentosum may be caused by genetic mutations in 8 genes, which produce the following enzymes: XPA, XPB, XPC, XPD, XPE, XPF, XPG and Pol η. XPA-XPF are nucleotide excision repair enzymes that repair UV light-damaged DNA and faulty proteins will allow the buildup of mutations caused by UV light. Pol η is a polymerase, which is an enzyme involved in DNA replication. There are many polymerases, but pol η is the enzyme that replicates UV light-damaged DNA. Mutations in this gene will produce a faulty pol η enzyme that cannot replicate DNA with UV light damage. Individuals with mutations of this gene have a subset of XP; XP-variant disease.[34][35] ## DNA repair defects and increased cancer risk[edit] Many cancer syndromes are due to an inherited impairment in DNA repair capability.[citation needed] When an inherited mutation is present in a DNA repair gene, the repair gene will either not be expressed or expressed in an altered form. Then the repair function will likely be deficient, and, as a consequence, DNA damages will tend to accumulate. Such DNA damages can cause errors during DNA synthesis leading to mutations, some of which may give rise to cancer. Germ-line DNA repair mutations that increase the risk of cancer are listed in the Table. Inherited DNA repair gene mutations that increase cancer risk DNA repair gene Protein Repair pathways affected* Cancers with increased risk ataxia telangiectasia mutated ATM Different mutations in ATM reduce HRR, SSA or NHEJ [36] leukemia, lymphoma, breast [36][37] Bloom syndrome BLM (helicase) HRR [38] leukemia, lymphoma, colon, breast, skin, lung, auditory canal, tongue, esophagus, stomach, tonsil, larynx, uterus [39] breast cancer 1 & 2 BRCA1 BRCA2 HRR of double strand breaks and daughter strand gaps[40] breast, ovarian [41] Fanconi anemia genes FANCA,B,C,D1,D2,E,F,G,I,J,L,M,N,O,P FANCA etc. HRR and TLS [42] leukemia, liver tumors, solid tumors many areas [43] Hereditary nonpolyposis colorectal cancer genes MSH2 MSH6 MLH1 PMS2 MSH2 MSH6 MLH1 PMS2 MMR [44] colorectal, endometrial, ovariain, gastrointestinal tract (stomach and small intestine, pancreas, biliary tract), urinary tract, brain (glioblastomas), and skin (keratoacanthomas and sebaceous adenomas) [45] Li-Fraumeni syndrome gene TP53 P53 Direct role in HRR, BER, NER and acts in DNA damage response[46] for those pathways and for NHEJ and MMR [47] sarcomas, breast cancers, brain tumors, and adrenocortical carcinomas [48] MRE11A MRE11 HRR and NHEJ [49] breast [50] MUTYH MUTYH glycosylase BER of A paired with 8-oxo-dG [51] colorectal, duodenal, ovarian, bladder and skin cancers [52] Nijmegen breakage syndrome NBS (NBN) NHEJ [53] lymphoid cancers [53] NTHL1 NTHL1 BER for Tg, FapyG, 5-hC, 5-hU in dsDNA[54] Colon cancer, endometrial cancer, duodenal cancer, basal-cell carcinoma[55] RECQL4 RECQ4 Helicase likely active in HRR [56] basal cell carcinoma, squamous cell carcinoma, intraepidermal carcinoma [57] Werner syndrome gene WRN Werner syndrome ATP-dependent helicase HRR, NHEJ, long patch BER [58] soft tissue sarcoma, colorectal, skin, thyroid, pancreas [59] Xeroderma pigmentosum genes XPA, XPB, XPD, XPF, XPG XPA XPB XPD XPF XPG Transcription coupled NER repairs the transcribed strands of transcriptionally active genes [60] skin cancer (melanoma and non-melanoma) [60] Xeroderma pigmentosum genes XPC, XPE (DDB2) XPC, XPE Global genomic NER, repairs damage in both transcribed and untranscribed DNA [61][62] skin cancer (melanoma and non-melanoma) [61][62] XPV (also called polymerase H) DNA polymerase eta (Pol η) Translesion synthesis (TLS) [63] skin cancers (basal cell, squamous cell, melanoma) [63] * The acronyms for DNA repair pathways are HRR homologous recombinational repair, SSA sub-pathway of HRR, NHEJ non-homologous end joining, BER base excision repair, TLS translesion synthesis, NER nucleotide excision repair, MMR mismatch repair. ## Genetic screening[edit] Genetic testing can be used to identify mutated genes or chromosomes that are passed through generations. People who test positive for having a genetic mutation are not necessarily condemned to develop the cancer linked with the mutation, however they possess an increased risk of developing cancer in comparison to the general population. It is advised that people get a genetic test if their family medical history includes: Multiple family members with cancer, someone in their family that got cancer at a particularly young age or by being part of a certain ethnic group.[64] An example of a direct to consumer genetic testing kit. This kit comes from the company 'MyGene'. The process of genetic screening is a simple, non-invasive procedure. However, before genes are tested for mutations the patient usually must go to a health care provider and go through a one-on-one consultation, where they discuss both the personal and family history of cancer. The medical professional can then assess the likelihood of the patient having the mutation and can guide them through the process that is genetic screening.[65] It is important that this consultation takes place because it ensures that the person gives informed consent to engage in genetic testing, is aware and understands the steps, benefits and limitations of the procedure and is more knowledgeable of the consequences of hearing test results.[66] The test can be done by using body fluids or cells of the patient, this includes; blood (which is the most common), saliva, amniotic fluid and even cells from the interior of the mouth gotten from a buccal swab. This material is then sent to a specialized genetics lab where technicians will examine it, the test results are sent back to the health provider who requested the analysis and results are discussed with the patient.[64] Direct to consumer testing can be obtained without a medical professional but is not recommended as the consumer loses the opportunity to discuss their decision with an educated professional.[67] According to the National Library of Medicine in the U.S. genetic testing in America costs in the price range of $100-$2000 depending on the type and intricacy of test.[68] ## Preventive actions[edit] Genetic testing is important as if a test comes out positive they are more aware of their own personal health and the health of immediate family members.[69] With the help and advice from a medical professional they can take steps to reduce their elevated risk of cancer development through: * Regular exercise * A healthy, balanced diet * Maintaining a healthy weight * Not smoking * Staying safe under the sun’s harmful rays [70] There are other forms of preventive actions, an example for Hereditary Breast and Ovarian Cancer would be to go through surgery: A hysterectomy is the removal of all or some of the uterus, whereas a mastectomy is removing a breast (double mastectomy meaning that both breasts are removed), this can often add years onto their life expectancy.[71] Another preventive measure is regular cancer screening and check-ups. If a person has Lynch’s syndrome then they should have a regular colonoscopy to examine if there is any change in the cells lining the intestinal wall, regular check-ups have been proven to add an average of 7 years onto the life expectancy of a person suffering from Lynch’s syndrome as early detection means the correct preventive actions and surgery can be taken quicker.[72] Regular breast screening is also recommended for women diagnosed with BRCA mutations, as well as that, recent studies show that men with increased risks of developing prostate cancer due to BRCA mutations can decrease their risk by taking aspirin.[73] Aspirin is hugely beneficial in lowering cancer prevalence; however, it must be taken regularly over at least a five-year period to have any effect.[74] ## Prevalence of genetic mutations in different ethnic groups[edit] Often genetic mutations are more common in certain ethnic groups, this is because a race can track their ancestors back to one geographic location, the mutated genes are then passed from ancestors down through generations which is why some ethnicities are more susceptible to mutations, thus increasing their chances of developing cancer [61]. As mentioned above, this can be useful as it can help health professionals assess a patient’s risk of having a mutation before they undergo testing.[65] Werner's Syndrome has a prevalence of 1 in 200,000 live births in the U.S., but it affects individuals in Japan in 1 in 20,000-40,000 cases.[75] 1 in 40 Ashkenazi Jews have a BRCA mutation, this is a huge contrast from the general population in the United States where 1 in 400 people are affected. Ashkenazi Jews are at high risk of developing hereditary breast and ovarian cancer and it is recommend that they undergo both genetic testing to see if they have a mutation and regular screening for cancer.[76] ## References[edit] 1. ^ Allgayer, Heike; Redher, Helga; Fulda, Simone (2009). Hereditary Tumors: From Genes to Clinical Consequences. Weinheim: Wiley-VCH. ISBN 9783527320288. 2. ^ a b Hodgson S (January 2008). "Mechanisms of inherited cancer susceptibility". J Zhejiang Univ Sci B. 9 (1): 1–4. doi:10.1631/jzus.B073001. PMC 2170461. PMID 18196605. 3. ^ Clark AS, Domchek SM (April 2011). "Clinical management of hereditary breast cancer syndromes". J Mammary Gland Biol Neoplasia. 16 (1): 17–25. doi:10.1007/s10911-011-9200-x. PMID 21360002. 4. ^ a b Lynch HT, Lynch PM, Lanspa SJ, Snyder CL, Lynch JF, Boland CR (July 2009). "Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications". Clin. Genet. 76 (1): 1–18. doi:10.1111/j.1399-0004.2009.01230.x. PMC 2846640. PMID 19659756. 5. ^ "Genetics". National Cancer Institute. 2015-04-22. Retrieved 2018-02-20. 6. ^ a b c Banks, KC; Moline, JJ; Marvin, ML; Newlin, AC; Vogel, KJ (March 2013). "10 rare tumors that warrant a genetics referral". Familial Cancer. 12 (1): 1–18. doi:10.1007/s10689-012-9584-9. PMID 23377869. 7. ^ Korde, Larissa A.; Gadalla, Shahinaz M. (2017-05-02). "Cancer Risk Assessment for the Primary Care Physician". Primary Care. 36 (3): 471–488. doi:10.1016/j.pop.2009.04.006. PMC 2713871. PMID 19616151. 8. ^ a b Anderson, Cindy Lou; Carie A Braun (2007). Pathophysiology: functional alterations in human health. Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 978-0-7817-6250-2. 9. ^ a b Lindor NM, Greene MH (July 1998). "The concise handbook of family cancer syndromes. Mayo Familial Cancer Program". Journal of the National Cancer Institute. 90 (14): 1039–71. doi:10.1093/jnci/90.14.1039. PMID 9672254. 10. ^ Moldovan GL, D'Andrea AD (2009). "How the fanconi anemia pathway guards the genome". Annu. Rev. Genet. 43: 223–49. doi:10.1146/annurev-genet-102108-134222. PMC 2830711. PMID 19686080. 11. ^ Tischkowitz MD, Hodgson SV (January 2003). "Fanconi anaemia". Journal of Medical Genetics. 40 (1): 1–10. doi:10.1136/jmg.40.1.1. PMC 1735271. PMID 12525534. 12. ^ Kee Y, D'Andrea AD (November 2012). "Molecular pathogenesis and clinical management of Fanconi anemia". Journal of Clinical Investigation. 122 (11): 3799–806. doi:10.1172/JCI58321. PMC 3484428. PMID 23114602. 13. ^ Kottemann MC, Smogorzewska A (January 2013). "Fanconi anaemia and the repair of Watson and Crick DNA crosslinks". Nature. 493 (7432): 356–63. Bibcode:2013Natur.493..356K. doi:10.1038/nature11863. PMC 3700363. PMID 23325218. 14. ^ Su X, Huang J (September 2011). "The Fanconi anemia pathway and DNA interstrand cross-link repair". Protein Cell. 2 (9): 704–11. doi:10.1007/s13238-011-1098-y. PMC 4875268. PMID 21948210. 15. ^ a b Half E, Bercovich D, Rozen P (2009). "Familial adenomatous polyposis". Orphanet J Rare Dis. 4: 22. doi:10.1186/1750-1172-4-22. PMC 2772987. PMID 19822006. 16. ^ Galiatsatos P, Foulkes WD (February 2006). "Familial adenomatous polyposis". American Journal of Gastroenterology. 101 (2): 385–98. PMID 16454848. 17. ^ Macrae F, du Sart D, Nasioulas S (2009). "Familial adenomatous polyposis". Best Pract Res Clin Gastroenterol. 23 (2): 197–207. doi:10.1016/j.bpg.2009.02.010. PMID 19414146. 18. ^ Petrucelli N, Daly MB, Feldman GL (May 2010). "Hereditary breast and ovarian cancer due to mutations in BRCA1 and BRCA2". Genet. Med. 12 (5): 245–59. doi:10.1097/GIM.0b013e3181d38f2f. PMID 20216074. 19. ^ Smith EC (2012). "An overview of hereditary breast and ovarian cancer syndrome". J Midwifery Womens Health. 57 (6): 577–84. doi:10.1111/j.1542-2011.2012.00199.x. PMID 23050669. 20. ^ Drescher KM, Sharma P, Lynch HT (2010). "Current hypotheses on how microsatellite instability leads to enhanced survival of Lynch Syndrome patients". Clin. Dev. Immunol. 2010: 1–13. doi:10.1155/2010/170432. PMC 2901607. PMID 20631828. 21. ^ Kunkel TA, Erie DA (2005). "DNA mismatch repair". Annu. Rev. Biochem. 74: 681–710. doi:10.1146/annurev.biochem.74.082803.133243. PMID 15952900. 22. ^ Kastrinos F, Syngal S (2011). "Inherited colorectal cancer syndromes". Cancer Journal. 17 (6): 405–15. doi:10.1097/PPO.0b013e318237e408. PMC 3240819. PMID 22157284. 23. ^ Neumann HP, Pawlu C, Peczkowska M, Bausch B, McWhinney SR, Muresan M, Buchta M, Franke G, Klisch J, Bley TA, Hoegerle S, Boedeker CC, Opocher G, Schipper J, Januszewicz A, Eng C (2004). "Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations". JAMA. 292 (8): 943–51. doi:10.1001/jama.292.8.943. PMID 15328326. 24. ^ Malkin D (April 2011). "Li-fraumeni syndrome". Genes Cancer. 2 (4): 475–84. doi:10.1177/1947601911413466. PMC 3135649. PMID 21779515. 25. ^ Bakry, D (2013). P53 in the Clinic: TP53 Germline Mutations: Genetics of Li–Fraumeni Syndrome. New York: Springer. pp. 167–188. ISBN 978-1-4614-3676-8. 26. ^ Birch JM (July 1994). "Familial cancer syndromes and clusters". British Medical Bulletin. 50 (3): 624–39. doi:10.1093/oxfordjournals.bmb.a072913. PMID 7987644. 27. ^ Quesnel S, Malkin D (August 1997). "Genetic predisposition to cancer and familial cancer syndromes". Pediatr. Clin. North Am. 44 (4): 791–808. doi:10.1016/s0031-3955(05)70530-7. PMID 9286285. 28. ^ Sampson JR, Jones N (2009). "MUTYH-associated polyposis". Best Pract Res Clin Gastroenterol. 23 (2): 209–18. doi:10.1016/j.bpg.2009.03.006. PMID 19414147. 29. ^ Manfredi M, Vescovi P, Bonanini M, Porter S (March 2004). "Nevoid basal cell carcinoma syndrome: a review of the literature". International Journal of Oral and Maxillofacial Surgery. 33 (2): 117–24. doi:10.1054/ijom.2003.0435. PMID 15050066. 30. ^ Lo Muzio L (2008). "Nevoid basal cell carcinoma syndrome (Gorlin syndrome)". Orphanet Journal of Rare Diseases. 3: 32. doi:10.1186/1750-1172-3-32. PMC 2607262. PMID 19032739. 31. ^ Richard, S; Gardie, B; Couvé, S; Gad, S (May 30, 2012). "Von Hippel-Lindau: How a rare disease illuminates cancer biology". Seminars in Cancer Biology. 23 (1): 26–37. doi:10.1016/j.semcancer.2012.05.005. PMID 22659535. 32. ^ Henry, Todd; Campell, James; Hawley, Arthur (1969). Todd-Sanford clinical diagnosis by laboratory methods, edited by Israel Davidsohn [and] John Bernard Henry (14th ed.). Philadelphia: Saunders. p. 555. ISBN 978-0-7216-2921-6. 33. ^ Wong WT, n E, Agró Coleman HR, et al. (February 2007). "Genotype–phenotype correlation in von Hippel–Lindau disease with retinal angiomatosis". Archives of Ophthalmology. 125 (2): 239–45. doi:10.1001/archopht.125.2.239. PMC 3019103. PMID 17296901. Archived from the original on 2008-12-12. Retrieved 2008-10-22. 34. ^ Lehmann AR, McGibbon D, Stefanini M (2011). "Xeroderma pigmentosum". Orphanet Journal of Rare Diseases. 6: 70. doi:10.1186/1750-1172-6-70. PMC 3221642. PMID 22044607. 35. ^ Niedernhofer LJ, Bohr VA, Sander M, Kraemer KH (2011). "Xeroderma pigmentosum and other diseases of human premature aging and DNA repair: molecules to patients". Mech. Ageing Dev. 132 (6–7): 340–7. doi:10.1016/j.mad.2011.06.004. PMC 3474983. PMID 21708183. 36. ^ a b Keimling M, Volcic M, Csernok A, Wieland B, Dörk T, Wiesmüller L (2011). "Functional characterization connects individual patient mutations in ataxia telangiectasia mutated (ATM) with dysfunction of specific DNA double-strand break-repair signaling pathways". FASEB Journal. 25 (11): 3849–60. doi:10.1096/fj.11-185546. PMID 21778326. 37. ^ Thompson LH, Schild D (2002). "Recombinational DNA repair and human disease". Mutat. Res. 509 (1–2): 49–78. doi:10.1016/s0027-5107(02)00224-5. PMID 12427531. 38. ^ Nimonkar AV, Ozsoy AZ, Genschel J, Modrich P, Kowalczykowski SC (2008). "Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair". Proc. Natl. Acad. Sci. U.S.A. 105 (44): 16906–11. Bibcode:2008PNAS..10516906N. doi:10.1073/pnas.0809380105. PMC 2579351. PMID 18971343. 39. ^ German J (1969). "Bloom's syndrome. I. Genetical and clinical observations in the first twenty-seven patients". American Journal of Human Genetics. 21 (2): 196–227. PMC 1706430. PMID 5770175. 40. ^ Nagaraju G, Scully R (2007). "Minding the gap: the underground functions of BRCA1 and BRCA2 at stalled replication forks". DNA Repair (Amst.). 6 (7): 1018–31. doi:10.1016/j.dnarep.2007.02.020. PMC 2989184. PMID 17379580. 41. ^ Lancaster JM, Powell CB, Chen LM, Richardson DL (2015). "Society of Gynecologic Oncology statement on risk assessment for inherited gynecologic cancer predispositions". Gynecol. Oncol. 136 (1): 3–7. doi:10.1016/j.ygyno.2014.09.009. PMID 25238946. 42. ^ Thompson LH, Hinz JM (2009). "Cellular and molecular consequences of defective Fanconi anemia proteins in replication-coupled DNA repair: mechanistic insights". Mutat. Res. 668 (1–2): 54–72. doi:10.1016/j.mrfmmm.2009.02.003. PMC 2714807. PMID 19622404. 43. ^ Alter BP (2003). "Cancer in Fanconi anemia, 1927-2001". Cancer. 97 (2): 425–40. doi:10.1002/cncr.11046. PMID 12518367. 44. ^ Meyer LA, Broaddus RR, Lu KH (2009). "Endometrial cancer and Lynch syndrome: clinical and pathologic considerations". Cancer Control. 16 (1): 14–22. doi:10.1177/107327480901600103. PMC 3693757. PMID 19078925. 45. ^ Carethers JM, Stoffel EM (2015). "Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of hereditary colon cancer". World Journal of Gastroenterology. 21 (31): 9253–61. doi:10.3748/wjg.v21.i31.9253. PMC 4541378. PMID 26309352. 46. ^ Kastan MB (2008). "DNA damage responses: mechanisms and roles in human disease: 2007 G.H.A. Clowes Memorial Award Lecture". Mol. Cancer Res. 6 (4): 517–24. doi:10.1158/1541-7786.MCR-08-0020. PMID 18403632. 47. ^ Viktorsson K, De Petris L, Lewensohn R (2005). "The role of p53 in treatment responses of lung cancer". Biochem. Biophys. Res. Commun. 331 (3): 868–80. doi:10.1016/j.bbrc.2005.03.192. PMID 15865943. 48. ^ Testa JR, Malkin D, Schiffman JD (2013). "Connecting molecular pathways to hereditary cancer risk syndromes". American Society of Clinical Oncology Educational Book. 33: 81–90. doi:10.1200/EdBook_AM.2013.33.81. PMC 5889618. PMID 23714463. 49. ^ Rapp A, Greulich KO (2004). "After double-strand break induction by UV-A, homologous recombination and nonhomologous end joining cooperate at the same DSB if both systems are available". Journal of Cell Science. 117 (Pt 21): 4935–45. doi:10.1242/jcs.01355. PMID 15367581. 50. ^ Bartkova J, Tommiska J, Oplustilova L, Aaltonen K, Tamminen A, Heikkinen T, Mistrik M, Aittomäki K, Blomqvist C, Heikkilä P, Lukas J, Nevanlinna H, Bartek J (2008). "Aberrations of the MRE11-RAD50-NBS1 DNA damage sensor complex in human breast cancer: MRE11 as a candidate familial cancer-predisposing gene". Mol Oncol. 2 (4): 296–316. doi:10.1016/j.molonc.2008.09.007. PMC 5527773. PMID 19383352. 51. ^ Markkanen E, Dorn J, Hübscher U (2013). "MUTYH DNA glycosylase: the rationale for removing undamaged bases from the DNA". Front Genet. 4: 18. doi:10.3389/fgene.2013.00018. PMC 3584444. PMID 23450852. 52. ^ Patel SG, Ahnen DJ (2012). "Familial colon cancer syndromes: an update of a rapidly evolving field". Curr Gastroenterol Rep. 14 (5): 428–38. doi:10.1007/s11894-012-0280-6. PMC 3448005. PMID 22864806. 53. ^ a b Chrzanowska KH, Gregorek H, Dembowska-Bagińska B, Kalina MA, Digweed M (2012). "Nijmegen breakage syndrome (NBS)". Orphanet Journal of Rare Diseases. 7: 13. doi:10.1186/1750-1172-7-13. PMC 3314554. PMID 22373003. 54. ^ Krokan HE, Bjørås M (2013). "Base excision repair". Cold Spring Harb Perspect Biol. 5 (4): a012583. doi:10.1101/cshperspect.a012583. PMC 3683898. PMID 23545420. 55. ^ Kuiper RP, Hoogerbrugge N (2015). "NTHL1 defines novel cancer syndrome". Oncotarget. 6 (33): 34069–70. doi:10.18632/oncotarget.5864. PMC 4741436. PMID 26431160. 56. ^ Singh DK, Ahn B, Bohr VA (2009). "Roles of RECQ helicases in recombination based DNA repair, genomic stability and aging". Biogerontology. 10 (3): 235–52. doi:10.1007/s10522-008-9205-z. PMC 2713741. PMID 19083132. 57. ^ Anbari KK, Ierardi-Curto LA, Silber JS, Asada N, Spinner N, Zackai EH, Belasco J, Morrissette JD, Dormans JP (2000). "Two primary osteosarcomas in a patient with Rothmund-Thomson syndrome". Clin. Orthop. Relat. Res. 378 (378): 213–23. doi:10.1097/00003086-200009000-00032. PMID 10986997. 58. ^ Bohr VA (2005). "Deficient DNA repair in the human progeroid disorder, Werner syndrome". Mutat. Res. 577 (1–2): 252–9. doi:10.1016/j.mrfmmm.2005.03.021. PMID 15916783. 59. ^ Monnat RJ (2010). "Human RECQ helicases: roles in DNA metabolism, mutagenesis and cancer biology". Semin. Cancer Biol. 20 (5): 329–39. doi:10.1016/j.semcancer.2010.10.002. PMC 3040982. PMID 20934517. 60. ^ a b Menck CF, Munford V (2014). "DNA repair diseases: What do they tell us about cancer and aging?". Genet. Mol. Biol. 37 (1 Suppl): 220–33. doi:10.1590/s1415-47572014000200008. PMC 3983582. PMID 24764756. 61. ^ a b Lehmann AR, McGibbon D, Stefanini M (2011). "Xeroderma pigmentosum". Orphanet Journal of Rare Diseases. 6: 70. doi:10.1186/1750-1172-6-70. PMC 3221642. PMID 22044607. 62. ^ a b Oh KS, Imoto K, Emmert S, Tamura D, DiGiovanna JJ, Kraemer KH (2011). "Nucleotide excision repair proteins rapidly accumulate but fail to persist in human XP-E (DDB2 mutant) cells". Photochem. Photobiol. 87 (3): 729–33. doi:10.1111/j.1751-1097.2011.00909.x. PMC 3082610. PMID 21388382. 63. ^ a b Opletalova K, Bourillon A, Yang W, Pouvelle C, Armier J, Despras E, Ludovic M, Mateus C, Robert C, Kannouche P, Soufir N, Sarasin A (2014). "Correlation of phenotype/genotype in a cohort of 23 xeroderma pigmentosum-variant patients reveals 12 new disease-causing POLH mutations". Hum. Mutat. 35 (1): 117–28. doi:10.1002/humu.22462. PMID 24130121. 64. ^ a b "Genetic Testing for Hereditary Cancer Syndromes". National Cancer Institute. 2013-04-22. Retrieved 2018-02-19. 65. ^ a b Foulkes, William D.; Knoppers, Bartha Maria; Turnbull, Clare (January 2016). "Population genetic testing for cancer susceptibility: founder mutations to genomes". Nature Reviews. Clinical Oncology. 13 (1): 41–54. doi:10.1038/nrclinonc.2015.173. ISSN 1759-4782. PMID 26483301. 66. ^ Reference, Genetics Home. "What is genetic testing?". Genetics Home Reference. Retrieved 2018-02-20. 67. ^ Myers, Melanie F.; Bernhardt, Barbara A. (June 2012). "Direct-to-consumer genetic testing: introduction to the special issue". Journal of Genetic Counseling. 21 (3): 357–360. doi:10.1007/s10897-012-9500-3. ISSN 1573-3599. PMID 22441809. 68. ^ Reference, Genetics Home. "What is the cost of genetic testing, and how long does it take to get the results?". Genetics Home Reference. Retrieved 2018-02-20. 69. ^ Robson, Mark E.; Bradbury, Angela R.; Arun, Banu; Domchek, Susan M.; Ford, James M.; Hampel, Heather L.; Lipkin, Stephen M.; Syngal, Sapna; Wollins, Dana S. (2015-11-01). "American Society of Clinical Oncology Policy Statement Update: Genetic and Genomic Testing for Cancer Susceptibility". Journal of Clinical Oncology. 33 (31): 3660–3667. doi:10.1200/JCO.2015.63.0996. ISSN 1527-7755. PMID 26324357. 70. ^ "Genetic testing for cancer risk". Cancer Research UK. 2015-06-02. Retrieved 2018-02-20. 71. ^ Schrag, D.; Kuntz, K. M.; Garber, J. E.; Weeks, J. C. (1997-05-15). "Decision analysis--effects of prophylactic mastectomy and oophorectomy on life expectancy among women with BRCA1 or BRCA2 mutations". The New England Journal of Medicine. 336 (20): 1465–1471. doi:10.1056/NEJM199705153362022. ISSN 0028-4793. PMID 9148160. 72. ^ Newton, K.; Green, K.; Lalloo, F.; Evans, D. G.; Hill, J. (January 2015). "Colonoscopy screening compliance and outcomes in patients with Lynch syndrome". Colorectal Disease. 17 (1): 38–46. doi:10.1111/codi.12778. ISSN 1463-1318. PMID 25213040. 73. ^ Cossack, Matthew; Ghaffary, Cameron; Watson, Patrice; Snyder, Carrie; Lynch, Henry (April 2014). "Aspirin use is associated with lower prostate cancer risk in male carriers of BRCA mutations". Journal of Genetic Counseling. 23 (2): 187–191. doi:10.1007/s10897-013-9629-8. ISSN 1573-3599. PMID 23881471. 74. ^ Thorat, Mangesh A.; Cuzick, Jack (December 2013). "Role of aspirin in cancer prevention". Current Oncology Reports. 15 (6): 533–540. doi:10.1007/s11912-013-0351-3. ISSN 1534-6269. PMID 24114189. 75. ^ Reference, Genetics Home. "Werner syndrome". Genetics Home Reference. Retrieved 2018-02-20. 76. ^ "Genetic risk, race and ethnicity \| Cancer Fighters Thrive Magazine". CancerCenter.com. Archived from the original on 2018-02-21. Retrieved 2018-02-20. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Cancer syndrome	c0027672	25,063	wikipedia	https://en.wikipedia.org/wiki/Cancer_syndrome	2021-01-18T18:59:30	{"mesh": ["D009386"], "umls": ["C0027672"], "orphanet": ["140162"], "wikidata": ["Q1348398"]}
A number sign (#) is used with this entry because of evidence that familial arrhythmogenic right ventricular dysplasia-5 (ARVD5) is caused by heterozygous mutation in the TMEM43 gene (612048) on chromosome 3p25. For a general phenotypic description and a discussion of genetic heterogeneity of this disorder, see ARVD1 (107970). Clinical Features Hodgkinson et al. (2013) reported the phenotype and natural history of 258 affected and 154 unaffected members of 15 Newfoundland families with arrhythmogenic right ventricular dysplasia (ARVD) that were previously studied by Merner et al. (2008) and found to carry an S358L mutation in the TMEM43 gene (612048.0001; see MOLECULAR GENETICS). Affected males were hospitalized 4 times more often than affected females and died younger; the temporal sequence from symptom onset to death was prolonged in affected females by 1 to 2 decades. The most prevalent electrocardiographic (ECG) manifestation was poor R-wave progression (PRWP), with affected males twice as likely to develop PRWP as affected females. Left ventricular enlargement occurred in 43% of affected individuals, with 11% fulfilling the criteria for dilated cardiomyopathy (CMD; see 115200). Ventricular ectopy on Holter monitor was common and occurred early; this was the most diagnostically useful clinical test, but no symptom or test could rule out the diagnosis. Hodgkinson et al. (2013) concluded that this ARVD subtype is a sex-influenced lethal arrhythmogenic cardiomyopathy, with a unique ECG finding, left ventricular dilation, heart failure, and early death. Mapping By linkage analysis in a large North American family, Ahmad et al. (1998) identified a novel locus for arrhythmogenic right ventricular dysplasia on 3p23. A peak 2-point lod score of 6.91 was obtained with marker D3S3613 at a recombination fraction of 0.0. Haplotype analysis identified a shared region of 9.3 cM between markers D3S3610 and D3S3659. Merner et al. (2008) performed fine mapping and compared haplotypes at chromosome 3p25 across clinically affected individuals from 15 unrelated Newfoundland families with autosomal dominant arrhythmogenic right ventricular dysplasia and narrowed the disease region to a 2.36-Mb interval containing 20 annotated genes. Molecular Genetics In 15 unrelated families from Newfoundland segregating autosomal dominant ARVD mapping to chromosome 3p25, Merner et al. (2008) performed bidirectional resequencing of 20 physical candidate ARVD5 genes and identified 1 rare variant, S358L in the TMEM43 gene (612048.0001), that was present in all 83 clinically affected individuals tested. The mutation was not found in 47 spouses or in 161 controls, and 35 (57%) of 61 'unaffected' individuals who carried the mutation were found to have clinical signs of ARVD on subsequent testing. Median age to develop an ARVD5-associated phenotype was 32 years for males and 44 years for females; penetrance was 100% in males and females by ages 63 and 76 years, respectively. Survival was significantly reduced in affected individuals, with a median survival of 41 and 71 years in affected males and females, respectively (relative risk, 6.8 times greater in affected males vs females). Christensen et al. (2011) analyzed the TMEM43 gene in 55 Danish probands who fulfilled the criteria for ARVD and 10 patients with only some features of ARVD, and identified 1 woman with the S358L variant, which was also detected in her affected mother and not found in 650 ethnically matched controls. The proband, who fulfilled criteria for ARVD, was negative for mutation in 6 known ARVD-associated genes and did not show any large genomic rearrangements. Immunostaining of patient myocardium for TMEM43 and plakoglobin (173325) showed reduced signals for both compared to controls, suggesting that TMEM43-associated ARVD shares a final common pathway with desmosome-associated ARVD. Baskin et al. (2013) analyzed DNA samples from 195 unrelated individuals with suspected ARVD for mutations in 4 ARVD-associated desmosomal genes as well as the TMEM43 gene. Twenty-eight patients had disease-causing mutations in DSP (125647), PKP2 (602861), DSC2 (125645), or DSG2 (125671). Six patients carried the S358L 'Newfoundland' mutation in TMEM43, including a 43-year-old New Zealand man who was not of Newfoundland descent. In the New Zealand patient, the mutation arose de novo and on a haplotype distinct from that of the Newfoundland patients. In addition, 5 different rare missense variants in the TMEM43 gene were identified (see, e.g., 612048.0004) in 5 patients, 2 of whom also carried a variant in PKP2 and DSP, respectively. INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Palpitations \- Presyncope or syncope \- Chest pain (more common in male patients) \- Heart failure (more common in male patients) \- Poor R-wave progression on electrocardiogram \- Premature ventricular contractions \- Couplets \- Bigeminy \- Ventricular tachycardia, nonsustained \- QRS greater than 110 ms \- Septal Q waves \- Left ventricular enlargement \- Dyskinesia, global or focal \- Right ventricular dilation (more common in male patients) \- Fractional shortening less than 25% (more common in male patients) \- Biventricular dilation (in some patients) \- Severe right ventricular atrophy with fibrofatty replacement (in some patients) MISCELLANEOUS \- Sudden cardiac death frequent in affected families \- Male patients have more severe disease than female patients MOLECULAR BASIS \- Caused by mutation in the transmembrane protein-43 gene (TMEM43, 612048.0001 ) ▲ 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	ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 5	c1862511	25,064	omim	https://www.omim.org/entry/604400	2019-09-22T16:11:59	{"doid": ["0110074"], "mesh": ["C566254"], "omim": ["107970", "604400"], "orphanet": ["217656"], "synonyms": ["Familial isolated ARVD", "ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY 5", "Familial isolated ARVC", "Alternative titles", "Familial isolated arrhythmogenic ventricular dysplasia", "Familial isolated arrhythmogenic ventricular cardiomyopathy", "Familial isolated arrhythmogenic right ventricular cardiomyopathy"], "genereviews": ["NBK1131"]}
Congenital microgastria is a rare malformation where the embryological development of the stomach is interrupted, leading to an abnormally small foregut in newborns and characterized by extreme feeding intolerance and malnutrition along with growth retardation and death if untreated. It is usually associated with multiple congenital anomalies. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Congenital microgastria	c0266150	25,065	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=199293	2021-01-23T17:03:31	{"umls": ["C0266150"], "icd-10": ["Q40.2"]}
Swyer-James syndrome is a rare condition in which the lung (or portion of the lung) does not grow normally and is slightly smaller than the opposite lung, usually following bronchiolitis in childhood. It is typically diagnosed after a chest X-ray or CT scan which shows unilateral pulmonary hyperlucency (one lung appearing less dense) and diminished pulmonary arteries. Affected individuals may not have any symptoms, or more commonly, they may have recurrent pulmonary infections and common respiratory symptoms. The cause of the condition is not completely understood. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Swyer-James syndrome	c0264395	25,066	gard	https://rarediseases.info.nih.gov/diseases/8324/swyer-james-syndrome	2021-01-18T17:57:27	{"mesh": ["D019568"], "umls": ["C0264395"], "synonyms": ["Swyer-James-MacLeod syndrome"]}
Primarily associated with bivalve molluscs (such as mussels, clams, oysters and scallops Shellfish poisoning SpecialtyToxicology Shellfish poisoning includes four syndromes that share some common features and are primarily associated with bivalve molluscs (such as mussels, clams, oysters and scallops.)[1] As filter feeders, these shellfish may accumulate toxins produced by microscopic algae, such as cyanobacteria, diatoms and dinoflagellates. ## Contents * 1 Syndromes * 2 See also * 3 References * 4 External links ## Syndromes[edit] The syndromes are: * Amnesic shellfish poisoning (ASP) * Diarrheal shellfish poisoning (DSP) * Neurotoxic shellfish poisoning (NSP) * Paralytic shellfish poisoning (PSP) ## See also[edit] * Cyanotoxin * Gonyaulax ## References[edit] 1. ^ Silver, Mary Wilcox (2006), "Protecting Ourselves from Shellfish Poisoning", American Scientist, 94 (4): 316–325, doi:10.1511/2006.60.316 ## External links[edit] Classification D * ICD-10: T61.2 * ICD-9-CM: 988.0 * MeSH: D057096 * DiseasesDB: 32220 * SNOMED CT: 426487006 External resources * eMedicine: emerg/528 * Human Illness Associated with Harmful Algae * 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 * t * e Consumer food safety Adulterants, food contaminants * 3-MCPD * Aldicarb * Antibiotic use in livestock * Cyanide * Formaldehyde * HGH controversies * Lead poisoning * Melamine * Mercury in fish * Sudan I Flavorings * Monosodium glutamate (MSG) * Salt * Sugar * High-fructose corn syrup Intestinal parasites and parasitic disease * Amoebiasis * Anisakiasis * Cryptosporidiosis * Cyclosporiasis * Diphyllobothriasis * Enterobiasis * Fasciolopsiasis * Fasciolosis * Giardiasis * Gnathostomiasis * Paragonimiasis * Toxoplasmosis * Trichinosis * Trichuriasis Microorganisms * Botulism * Campylobacter jejuni * Clostridium perfringens * Cronobacter * Enterovirus * Escherichia coli O104:H4 * Escherichia coli O157:H7 * Hepatitis A * Hepatitis E * Listeria * Norovirus * Rotavirus * Salmonella * Vibrio cholerae Pesticides * Chlorpyrifos * DDT * Lindane * Malathion * Methamidophos Preservatives * Benzoic acid * Ethylenediaminetetraacetic acid (EDTA) * Sodium benzoate Sugar substitutes * Acesulfame potassium * Aspartame * Saccharin * Sodium cyclamate * Sorbitol * Sucralose Toxins, poisons, environment pollution * Aflatoxin * Arsenic contamination of groundwater * Benzene in soft drinks * Bisphenol A * Dieldrin * Diethylstilbestrol * Dioxin * Mycotoxins * Nonylphenol * Shellfish poisoning Food contamination incidents * Devon colic * Swill milk scandal * Esing Bakery incident * 1858 Bradford sweets poisoning * 1900 English beer poisoning * Morinaga Milk arsenic poisoning incident * Minamata disease * 1971 Iraq poison grain disaster * Toxic oil syndrome * 1985 diethylene glycol wine scandal * UK mad cow disease outbreak * 1993 Jack in the Box E. coli outbreak * 1996 Odwalla E. coli outbreak * 2006 North American E. coli outbreaks * ICA meat repackaging controversy * 2008 Canada listeriosis outbreak * 2008 Chinese milk scandal * 2008 Irish pork crisis * 2008 United States salmonellosis outbreak * 2011 Germany E. coli outbreak * 2011 United States listeriosis outbreak * 2013 Bihar school meal poisoning * 2013 horse meat scandal * 2015 Mozambique beer poisoning * 2017 Brazil weak meat scandal * 2017–18 South African listeriosis outbreak * 2018 Australian rockmelon listeriosis outbreak * 2018 Australian strawberry contamination * Food safety incidents in China * Food safety incidents in Taiwan * Food safety in Australia * Foodborne illness * outbreaks * death toll * United States Regulation, standards, watchdogs * Acceptable daily intake * E number * Food labeling regulations * Food libel laws * International Food Safety Network * ISO 22000 * Nutrition facts label * Organic certification * The Non-GMO Project * Quality Assurance International * Food Standards Agency Institutions * Institute for Food Safety and Health * European Food Safety Authority * International Food Safety Network * Spanish Agency for Food Safety and Nutrition * Food Information and Control Agency (Spain) * Centre for Food Safety (Hong Kong) * Ministry of Food and Drug Safety (South Korea) * v * t * e Seafood Fish * Anchovy * Barramundi * Billfish * Carp * Catfish * Cod * Eel * Flatfish * Flounder * Herring * Mackerel * Salmon * Sardine * Shark * Sturgeon * Swordfish * Tilapia * Trout * Tuna * Whitebait Shellfish * Abalone * Cockles * Conch * Crab meat * Crayfish * Geoduck * Krill * Lobster * Mussels * Oysters * Scallops * Shrimp * Sea urchins * Crustaceans * Molluscs Other seafood * Edible seaweed * Jellyfish * Marine mammals * Octopus * Sea cucumber * Squid * Whale meat * Sea vegetables * Algae * List of seafoods * more... Processed seafood * Caviar * Dried fish * Hutki Shira * Canned fish * Cod liver oil * Cured fish * Fermented fish * Fish fillet * Fish head * Fish oil * Fish sauce * Fish paste * Fish steak * Fish stock * Lutefisk * Salted fish * Salted squid * Shark liver oil * Shrimp paste * Smoked fish * Stockfish * Surimi * Roe * more... Seafood dishes * List of seafood dishes * List of crab dishes * List of fish dishes * List of raw fish dishes * List of tuna dishes * Bisque * Chowder * Fish and chips * Fish pie * Fish soup * Fried fish * Seafood boil * Shark fin soup * Sushi * more... Health hazards * Ciguatera * Fish diseases and parasites * Mercury in fish * Metagonimiasis * Scombroid food poisoning * Shellfish poisoning Advisory services * Seafood mislabelling * Sustainable seafood * Sustainable seafood advisory lists and certification Animal welfare * Declawing of crabs * Eyestalk ablation * Eating live seafood * Live fish trade * Pain in fish * Pain in crustaceans * Shark finning Related topics * Fish preservation * Fish processing * Gathering seafood by hand * History of seafood * History of sushi * List of seafood companies * Pescetarianism * Raw bar * Salmon cannery * Seafood restaurant * Food portal * Category: Seafood Authority control * NDL: 01085140 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Shellfish poisoning	c1960100	25,067	wikipedia	https://en.wikipedia.org/wiki/Shellfish_poisoning	2021-01-18T18:54:45	{"mesh": ["D057096"], "icd-9": ["988.0"], "icd-10": ["T61.2"], "wikidata": ["Q384821"]}
A rare intestinal disease characterized by impaired absorption of starch and short polymers of glucose due to primary small intestinal glucoamylase deficiency. Patients present in infancy or early childhood with chronic diarrhea, abdominal distention, and bloating. Levels of pancreatic amylase are typically normal, and histopathological analysis shows normal morphology of the intestinal mucosa. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Chronic diarrhea due to glucoamylase deficiency	c4275068	25,068	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=103907	2021-01-23T18:13:38	{"icd-10": ["E74.3"], "synonyms": ["Maltase-glucoamylase deficiency"]}
Rosenberg et al. (1989) described a family in which 14 persons in 5 generations suffered from severe dementia and parkinsonism. In 2 autopsied members of the family, neuropathologic correlations consisted of extracellular hyaline eosinophilic, congophilic amyloid plaques in the cerebral cortex, basal ganglia, thalamus, and substantia nigra, in descending order of frequency, as well as atrophy and gliosis of the basal ganglia and substantia nigra. The extracellular plaque did not stain with antibody raised against the prion protein or with 2 separate anti-amyloid A4 antibodies. Although no instance of male-to-male transmission was identified in the family, the inheritance was thought to be autosomal dominant. Both Alzheimer disease and Gerstmann-Straussler syndrome could be excluded by the properties of the amyloid. Neuro \- Severe dementia \- Parkinsonism Lab \- Extracellular hyaline eosinophilic, congophilic amyloid plaques in the cerebral cortex, basal ganglia, thalamus, and substantia nigra \- atrophy and gliosis of the basal ganglia and substantia nigra Inheritance \- Autosomal dominant ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	DEMENTIA/PARKINSONISM WITH NON-ALZHEIMER AMYLOID PLAQUES	c1852223	25,069	omim	https://www.omim.org/entry/125320	2019-09-22T16:42:32	{"mesh": ["C565115"], "omim": ["125320"]}
Goldmann-Favre syndrome, also known as the severe form of enhanced S-cone syndrome, is a inherited eye disease that affects the light-sensitive part of the eye (retina). Within the retina are "red," "blue," and "green" cones which allow us to see colors properly; and rods which allows us to see in dim light. People with Goldmann-Favre syndrome are born with an overabundance of blue cones, a reduced number of red and green cones, and few, if any, functional rods. As a result they experience an increased sensitivity to blue light, varying degrees of red and green cone vision, night blindness occurring from early life, vision loss, and retinal degeneration. Goldmann-Favre syndrome can be caused by mutations in the NR2E3 gene and is inherited in an autosomal recessive fashion.Treatment may include laser photocoagulation and medication, such as acetazolamide, dorzolamide and cyclosporin A. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Goldmann-Favre syndrome	c0339541	25,070	gard	https://rarediseases.info.nih.gov/diseases/10781/goldmann-favre-syndrome	2021-01-18T18:00:14	{"mesh": ["C564835"], "omim": ["268100"], "orphanet": ["53540"], "synonyms": ["Enhanced S-cone syndrome", "Retinoschisis with early hemeralopia", "Favre hyaloideoretinal degeneration"]}
Microcephalic osteodysplastic primordial dwarfism type II (MOPDII) is a condition characterized by short stature (dwarfism) with other skeletal abnormalities (osteodysplasia) and an unusually small head size (microcephaly). The growth problems in MOPDII are primordial, meaning they begin before birth, with affected individuals showing slow prenatal growth (intrauterine growth retardation). After birth, affected individuals continue to grow at a very slow rate. The final adult height of people with this condition ranges from 20 inches to 40 inches. Other skeletal abnormalities in MOPDII include abnormal development of the hip joints (hip dysplasia), thinning of the bones in the arms and legs, an abnormal side-to-side curvature of the spine (scoliosis), and shortened wrist bones. In people with MOPDII head growth slows over time; affected individuals have an adult brain size comparable to that of a 3-month-old infant. However, intellectual development is typically normal. People with this condition have a high-pitched, nasal voice and some have a narrowing of the voicebox (subglottic stenosis). Facial features characteristic of MOPDII include a prominent nose, full cheeks, a long midface, and a small jaw. Other signs and symptoms seen in some people with MOPDII include small teeth (microdontia) and farsightedness. Over time, affected individuals may develop areas of abnormally light or dark skin coloring (pigmentation). Many individuals with MOPDII have blood vessel abnormalities. For example, some affected individuals develop a bulge in one of the blood vessels at the center of the brain (intracranial aneurysm). These aneurysms are dangerous because they can burst, causing bleeding within the brain. Some affected individuals have Moyamoya disease, in which arteries at the base of the brain are narrowed, leading to restricted blood flow. These vascular abnormalities are often treatable, though they increase the risk of stroke and reduce the life expectancy of affected individuals. ## Frequency MOPDII appears to be a rare condition, although its prevalence is unknown. ## Causes Mutations in the PCNT gene cause MOPDII. The PCNT gene provides instructions for making a protein called pericentrin. Within cells, this protein is located in structures called centrosomes. Centrosomes play a role in cell division and the assembly of microtubules. Microtubules are fibers that help cells maintain their shape, assist in the process of cell division, and are essential for the transport of materials within cells. Pericentrin acts as an anchoring protein, securing other proteins to the centrosome. Through its interactions with these proteins, pericentrin plays a role in regulation of the cell cycle, which is the cell's way of replicating itself in an organized, step-by-step fashion. PCNT gene mutations lead to the production of a nonfunctional pericentrin protein that cannot anchor other proteins to the centrosome. As a result, centrosomes cannot properly assemble microtubules, leading to disruption of the cell cycle and cell division. Impaired cell division causes a reduction in cell production, while disruption of the cell cycle can lead to cell death. This overall reduction in the number of cells leads to short bones, microcephaly, and the other signs and symptoms of MOPDII. ### Learn more about the gene associated with Microcephalic osteodysplastic primordial dwarfism type II * PCNT ## 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	Microcephalic osteodysplastic primordial dwarfism type II	c0432246	25,071	medlineplus	https://medlineplus.gov/genetics/condition/microcephalic-osteodysplastic-primordial-dwarfism-type-ii/	2021-01-27T08:25:04	{"gard": ["9844"], "mesh": ["C565898"], "omim": ["210720"], "synonyms": []}
## Summary ### Clinical characteristics. MBD5 haploinsufficiency is a neurodevelopmental disorder characterized by developmental delay / intellectual disability, severe speech impairment, seizures, sleep disturbances, and abnormal behaviors. Most children lack speech entirely or have single words, short phrases, or short sentences. Seizures are present in about 80%; onset is usually around age two years. Sleep disturbances, present in about 80%, can result in excessive daytime drowsiness. Abnormal behaviors can include autistic-like behaviors (80%) and self-injury and aggression (60%). ### Diagnosis/testing. Most commonly the diagnosis of MBD5 haploinsufficiency is established in a proband by detection of one of the following alterations on molecular genetic testing: * Deletion of 2q23.1 that encompasses all or part of MBD5 (~90% of affected individuals) * Intragenic deletion involving one or more exons of MBD5 (~5%) * A heterozygous pathogenic sequence variant in MBD5 (~5%) Rarely, an apparently balanced complex chromosome rearrangement of the 2q23.1 region involving MBD5 is causative. ### Management. Treatment of manifestations: A multidisciplinary approach that typically includes specialists in clinical genetics, neurology, child development, behavioral therapy, nutrition/feeding, speech and language therapy, and occupational and physical therapy is recommended. Infants benefit from enrollment in an early-intervention program, and school-age children benefit from an individualized educational program. Speech therapy (including nonverbal methods of communication) should be introduced early. Seizures, behavior problems, and sleep disturbances are treated in a routine manner. Surveillance: Periodic neurodevelopmental and behavioral evaluations to assist in the management of cognitive and behavioral problems. ### Genetic counseling. MBD5 haploinsufficiency is inherited in an autosomal dominant manner. Typically, deletion of 2q23.1 is de novo; in some instances, an MBD5 pathogenic deletion or MBD5 sequence variant is inherited from a parent who is mildly affected. Rarely, parent-to-child transmission of an unbalanced derivative chromosome involving the 2q23.1 region occurs. Once the genetic alteration resulting in MBD5 haploinsufficiency has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible. ## Diagnosis ### Suggestive Findings MBD5 haploinsufficiency, a neurodevelopmental disorder, should be suspected in individuals with the following findings [Talkowski et al 2011, Hodge et al 2014, Mullegama & Elsea 2016]. Neurologic * Intellectual disability (ID), usually moderate to severe * Motor delays * Severe speech impairment * Seizures * Sleep disturbance * Hypotonia * Feeding difficulties, often related to hypotonia Behavior * Short attention span * Autistic-like behaviors that include gaze avoidance, inattention, and repetitive behaviors * Self-injury and/or aggressive behaviors ### Establishing the Diagnosis The diagnosis of MBD5 haploinsufficiency is established in a proband with one of the following (see Table 1): * Deletion of 2q23.1 that encompasses all or part of MBD5 (~90% of affected individuals) * Intragenic deletion involving one or more exons of MBD5 (~5%) * A heterozygous pathogenic sequence variant in MBD5 (~5%) * Rarely, an apparently balanced complex chromosome rearrangement of the 2q23.1 region involving MBD5 Molecular genetic testing approaches can include a combination of genomic testing (chromosomal microarray analysis [CMA] or more comprehensive genomic testing) and gene-targeted testing (multigene panel or single-gene testing). Gene-targeted testing requires the clinician to hypothesize which gene(s) are likely involved, whereas genomic testing may not. Because many inherited disorders share the phenotypic findings of ID, seizures, and behavior problems, most children with MBD5 haploinsufficiency are diagnosed by the following recommended testing (CMA and/or a multigene panel) or testing to be considered (comprehensive genomic testing sequencing). #### Recommended First-Tier Testing Chromosomal microarray analysis (CMA) should be the first genetic test as about 90% of MBD5 haploinsufficiency is caused by large, nonrecurrent deletions, which cannot be detected by sequence analysis of MBD5. Note: The phenotype of significantly larger or smaller deletions within this region may be clinically distinct from MBD5 haploinsufficiency (see Genetically Related Disorders). #### Options for Second-Tier Testing A multigene panel that includes MBD5 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 or genome sequencing may be considered if the phenotype alone is insufficient to support gene-targeted testing. For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. Note: Single-gene testing (sequence analysis of MBD5 followed by gene-targeted deletion/duplication analysis* (if no pathogenic variant is found) may be considered in individuals with features that are highly suggestive of MBD5 haploinsufficiency. However, because many of these features overlap with those of many other genetic disorders with ID, seizures, and behavior issues, a multigene panel or exome sequencing is typically used in lieu of single-gene testing. Gene-targeted deletion/duplication analysis should include evaluation of exon 1, which is noncoding, since deletions that include only exon 1 result in MBD5 haploinsufficiency. ### Table 1. Molecular Genetic Testing Used in MBD5 Haploinsufficiency View in own window Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method MBD5CMA 3~90% Gene-targeted deletion/duplication analysis 4~5% Sequence analysis 5~5% 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\. CMA identifies deletion of 2q23.1 (de novo terminal and interstitial deletions). 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. 5\. 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. ## Clinical Characteristics ### Clinical Description MBD5 haploinsufficiency is a neurodevelopmental disorder that comprises developmental delay / intellectual disability (ID), severe speech impairment, seizures, sleep disturbances, and behavioral problems with autistic features [Jaillard et al 2009, van Bon et al 2010, Talkowski et al 2011, Noh & Graham 2012]. Developmental delays, evident in all children with MBD5 haploinsufficiency within the first year of life, include delays in gross motor and fine motor development, receptive and expressive language development, and acquisition of social skills. Children typically acquire new skills, without evidence of psychomotor regression. Motor delays with poor coordination and broad-based/ataxic gait are seen in more than 70% of individuals. The average age of walking is two to three years [van Bon et al 2010, Talkowski et al 2011, Hodge et al 2014]. Language development is severely impaired [van Bon et al 2010]. Most reported children lack speech entirely [Talkowski et al 2011] or have single words or short (2- to 3-word) phrases [Bonnet et al 2013] or (2- to 6-word) sentences [Hodge et al 2014]. Seizures occur in more than 80% of children [Talkowski et al 2011, Hodge et al 2014]. Onset of seizures is usually around age two years [Jaillard et al 2009, van Bon et al 2010, Williams et al 2010, Chung et al 2011, Talkowski et al 2011, Motobayashi et al 2012, Noh & Graham 2012, Bonnet et al 2013, Shichiji et al 2013, Hodge et al 2014]. Although seizure types have not been well characterized, typically only one seizure type is observed in an individual. Seizure types have included absence spells and generalized tonic-clonic, atonic, sleep-related, and startle-induced atonic seizures [Jaillard et al 2009, van Bon et al 2010, Williams et al 2010, Chung et al 2011, Talkowski et al 2011, Motobayashi et al 2012, Noh & Graham 2012, Bonnet et al 2013, Hodge et al 2014]. In the few instances in which EEG studies have been performed, patterns were nonspecific; however, a few individuals were reported to have focal spikes and spike-wave complexes [van Bon et al 2010, Talkowski et al 2011, Hodge et al 2014]. Sleep disturbances, present in about 80% of affected children, include frequent nighttime waking, apparent night terrors in the early part of sleep, and waking in the early hours of the morning [Jaillard et al 2009, van Bon et al 2010, Williams et al 2010, Chung et al 2011, Talkowski et al 2011, Noh & Graham 2012, Bonnet et al 2013, Hodge et al 2014, Mullegama et al 2014]. Many exhibit excessive daytime sleepiness [Mullegama et al 2015b]. Behavior problems (observed in MBD5 haploinsufficiency and other forms of syndromic autism) [Talkowski et al 2011, Hodge et al 2014] include the following: Short attention span and autistic-like behaviors (gaze avoidance, inattention, and repetitive behaviors) [Tan et al 2014] and stereotypic and repetitive behaviors (e.g., teeth grinding, chewing of the hands, and repetitive hand movements) are seen in more than 80% of affected individuals. * Self-injury and aggression are seen in more than 60% of individuals. * Other behaviors mentioned in approximately 9% of reported individuals include anxiety, hyperactivity, inappropriate happy demeanor, and social withdrawal. Other findings [Talkowski et al 2011, Hodge et al 2014] * Feeding difficulties and constipation, likely related to hypotonia, in more than 90% of infants * Mild dysmorphic features (seen in the majority of affected individuals) that may include broad forehead, thick / highly arched eyebrows, outer ear abnormalities (e.g., forward-facing large earlobes, protruding ears, cupped ears), short nose, depressed or wide nasal bridge, downturned corners of the mouth, everted vermilion of the lower lip, tented and thin vermilion of the upper lip * Skeletal abnormalities (observed in 65 individuals with MBD5 haploinsufficiency) including: small hands and feet (~75%), fifth finger clinodactyly (~70%), generalized brachydactyly (~41%), short fifth digit of the hands and feet (40%), and sandal gap (~33%) [Talkowski et al 2011] Other musculoskeletal abnormalities mentioned in at least two affected individuals each are hip dysplasia, joint laxity, and scoliosis. * Cardiovascular abnormalities (seen in ~10%) including atrial septal defect, ventricular septal defect, and pulmonary valve stenosis ### Genotype-Phenotype Correlations Current data show that MBD5 haploinsufficiency is due to decreased MBD5 dosage, which can result from large or small deletions involving MBD5 or pathogenic sequence variants in MBD5. Although no genotype-phenotype correlations distinguish individuals with pathogenic sequence variants from those with deletions, individuals with larger deletions involving multiple genes may exhibit a more severe phenotype. ### Penetrance Clinical features of MBD5 haploinsufficiency are apparent in all individuals with de novo inactivation of one MBD5 allele; however, both phenotypic heterogeneity and variable expressivity are observed. In some instances, probands have inherited the variant (small MBD5 deletion or duplication or missense variant) from a mildly affected parent in an autosomal dominant manner, suggesting that incomplete penetrance and/or variable expressivity may be associated with this condition [Talkowski et al 2011, Hodge et al 2014]. ### Nomenclature MBD5 haploinsufficiency was first recognized when overlapping deletions of 2q23.1 were identified in individuals with intellectual disability (ID) and "pseudo-Angelman" phenotypes using array comparative genomic hybridization (array-CGH) [Jaillard et al 2009]. This disorder was initially called 2q23.1 deletion syndrome; however, delineation of the smallest region of overlap among individuals with a 2q23.1 deletion confirmed that haploinsufficiency of MBD5 is responsible for the disorder. In addition, subsequent identification of heterozygous pathogenic sequence variants in MBD5 further supports the use of the term "MBD5 haploinsufficiency." OMIM uses an outdated term for MBD5 haploinsufficiency: "mental retardation, autosomal dominant 1"; MRD1 (OMIM 156200). ### Prevalence The prevalence of MBD5 haploinsufficiency is not known. Because many individuals with MBD5 haploinsufficiency may go undiagnosed, the prevalence may be greater than observed to date. Approximately 1% of 4,808 individuals (from 3 cohorts) ascertained for autism spectrum disorder were found to have MBD5 haploinsufficiency when assessed for CNVs involving MBD5 and for MBD5 sequence variants not present in controls [Talkowski et al 2011]. MBD5 haploinsufficiency has been identified worldwide and is present in all ethnic groups. ## Differential Diagnosis The differential diagnosis of MBD5 haploinsufficiency is broad due to the variable spectrum and presence of relatively common abnormal phenotypes that occur in affected individuals (e.g., developmental delay, learning problems, neuropsychiatric disorders). All manifestations of the MBD5 haploinsufficiency can also be seen in individuals with other genomic disorders. Significant similarity in phenotypic features is observed between MBD5 haploinsufficiency and other neurodevelopmental syndromes. Specific disorders to consider in the differential diagnosis of MBD5 haploinsufficiency include the following: * Smith-Magenis syndrome (SMS) * Angelman syndrome (AS) * Pitt-Hopkins syndrome * Rett syndrome * Fragile X syndrome * Kleefstra syndrome * Koolen-De Vries syndrome ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with MBD5 haploinsufficiency, the following evaluations are recommended: * Physical and neurologic examination * Developmental assessment including assessment by a physical therapist and/or occupational therapist * Speech evaluation including feeding evaluation and nutrition consultation as needed * Hearing assessment (as part of the routine evaluation of children with speech delay) * EEG if seizures are suspected * Cardiac evaluation * Sleep history * Behavioral assessment * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations A multidisciplinary approach to manage the features and specific issues identified is recommended. Specialists in the following fields are often involved: clinical genetics, neurology, child development, behavioral therapy, nutrition/feeding, speech and language therapy, and occupational and physical therapy. Neurologic * Infants benefit from enrollment in an early-intervention program. * School-age children benefit from an individualized educational program. * Speech therapy with early introduction of nonverbal methods of communication (e.g., sign language and computer-assisted technologies) is appropriate given the high risk for poor or absent speech. * Antiepileptic drugs (AEDs) such as valproate, clonazepam, zonisamide, and clobazam appear to be effective in reducing the incidence of seizures [Jaillard et al 2009, van Bon et al 2010, Williams et al 2010, Chung et al 2011, Talkowski et al 2011, Motobayashi et al 2012, Noh & Graham 2012, Bonnet et al 2013, Hodge et al 2014]. No information is available on response to specific AEDs. Behavior * Routine management of behavioral issues associated with severe intellectual disability and/or autism spectrum disorder is indicated. * Management of sleep disturbance through a combined approach of targeted sleep hygiene (to develop firm daily schedules) and use of daily medications such as melatonin, clonidine, and trazodone may be considered [Mullegama et al 2015b]. * Routine management is necessary for constipation (which can affect behavior). ### Surveillance Appropriate surveillance includes: * Periodic neurodevelopmental and behavioral evaluations to assist in the management of cognitive and behavioral problems; * Periodic reevaluations by a clinical geneticist to provide new recommendations and information regarding MBD5 haploinsufficiency. ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	MBD5 Haploinsufficiency	c4304532	25,072	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK390803/	2021-01-18T21:14:07	{"synonyms": ["2q23.1 Microdeletion Syndrome", "MBD5-Associated Neurodevelopmental Disorders (MAND)"]}
Carnitine-acylcarnitine translocase (CACT) deficiency is a condition that prevents the body from using certain fats for energy, particularly during periods without food (fasting). Signs and symptoms of this disorder usually begin soon after birth and may include breathing problems, seizures, and an irregular heartbeat (arrhythmia). Affected individuals typically have low blood sugar (hypoglycemia) and a low level of ketones, which are produced during the breakdown of fats and used for energy. Together these signs are called hypoketotic hypoglycemia. People with CACT deficiency also usually have excess ammonia in the blood (hyperammonemia), an enlarged liver (hepatomegaly), and a weakened heart muscle (cardiomyopathy). Many infants with CACT deficiency do not survive the newborn period. Some affected individuals have a less severe form of the condition and do not develop signs and symptoms until early childhood. These individuals are at risk for liver failure, nervous system damage, coma, and sudden death. ## Frequency CACT deficiency is very rare; at least 30 cases have been reported. ## Causes Mutations in the SLC25A20 gene cause CACT deficiency. This gene provides instructions for making a protein called carnitine-acylcarnitine translocase (CACT). This protein is essential for fatty acid oxidation, a multistep process that breaks down (metabolizes) fats and converts them into energy. Fatty acid oxidation takes place within mitochondria, which are the energy-producing centers in cells. A group of fats called long-chain fatty acids must be attached to a substance known as carnitine to enter mitochondria. Once these fatty acids are joined with carnitine, the CACT protein transports them into mitochondria. Fatty acids are a major source of energy for the heart and muscles. During periods of fasting, fatty acids are also an important energy source for the liver and other tissues. Although mutations in the SLC25A20 gene change the structure of the CACT protein in different ways, they all lead to a shortage (deficiency) of the transporter. Without enough functional CACT protein, long-chain fatty acids cannot be transported into mitochondria. As a result, these fatty acids are not converted to energy. Reduced energy production can lead to some of the features of CACT deficiency, such as hypoketotic hypoglycemia. Fatty acids and long-chain acylcarnitines (fatty acids still attached to carnitine) may also build up in cells and damage the liver, heart, and muscles. This abnormal buildup causes the other signs and symptoms of the disorder. ### Learn more about the gene associated with Carnitine-acylcarnitine translocase deficiency * SLC25A20 ## 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	Carnitine-acylcarnitine translocase deficiency	c0342791	25,073	medlineplus	https://medlineplus.gov/genetics/condition/carnitine-acylcarnitine-translocase-deficiency/	2021-01-27T08:25:24	{"gard": ["1123"], "mesh": ["C562812"], "omim": ["212138"], "synonyms": []}
This article's lead section may be too short to adequately summarize its key points. Please consider expanding the lead to provide an accessible overview of all important aspects of the article. (June 2019) Bone disease SpecialtyRheumatology Bone disease refers to the medical conditions which affect the bone. ## Contents * 1 Terminology * 2 Bone and cartilage disorders * 3 List * 3.1 A * 3.2 B * 3.3 C * 3.4 F * 3.5 G * 3.6 H * 3.7 K * 3.8 M * 3.9 N * 3.10 O * 3.11 P * 3.12 R * 3.13 S * 3.14 W * 4 See also * 5 References * 6 External links ## Terminology[edit] Further information: Osteopathy A bone disease is also called an "osteopathy", but because the term osteopathy is often used to refer to an alternative health-care philosophy, use of the term can cause some confusion. ## Bone and cartilage disorders[edit] Main article: Osteochondrodysplasia Osteochondrodysplasia is a general term for a disorder of the development of bone and cartilage. ## List[edit] ### A[edit] * Ambe * Avascular necrosis or Osteonecrosis * Arthritis ### B[edit] * Bone spur (Osteophytes) * Colon cancer[citation needed] ### C[edit] * Craniosynostosis * Coffin–Lowry syndrome ### F[edit] * Fibrodysplasia ossificans progressiva * Fibrous dysplasia * Fong disease (or Nail–patella syndrome) * Fracture ### G[edit] * Giant cell tumor of bone * Greenstick fracture * Gout ### H[edit] * Hypophosphatasia * Hereditary multiple exostoses ### K[edit] * Klippel–Feil syndrome ### M[edit] * Metabolic bone disease * Multiple myeloma ### N[edit] * Nail–patella syndrome ### O[edit] * Osteitis * Osteitis deformans (or Paget's disease of bone) * Osteitis fibrosa cystica (or Osteitis fibrosa, or Von Recklinghausen's disease of bone) * Osteitis pubis * Condensing osteitis (or Osteitis condensas) * Osteochondritis dissecans * Osteochondroma (bone tumor) * Osteogenesis imperfecta * Osteomalacia * Osteomyelitis * Osteopenia * Osteopetrosis * Osteoporosis ### P[edit] * Porotic hyperostosis * Primary hyperparathyroidism ### R[edit] * Renal osteodystrophy ### S[edit] * Salter–Harris fracture * Scoliosis ### W[edit] * Water on the knee ## See also[edit] * Osteoimmunology ## References[edit] ## External links[edit] Classification D * ICD-10: M80-M90 * ICD-9-CM: 730-733 * MeSH: D001847 * https://www.nlm.nih.gov/medlineplus/bonediseases.html * 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 This article about a disease of musculoskeletal and connective tissue is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Bone disease	c0005940	25,074	wikipedia	https://en.wikipedia.org/wiki/Bone_disease	2021-01-18T18:59:38	{"mesh": ["D001847"], "umls": ["C0005940"], "icd-9": ["730", "733"], "wikidata": ["Q4941552"]}
Idiopathic bilateral vestibulopathy is a rare otorhinolaryngologic disease characterized by dysfunction of both peripheral labyrinths or of the eighth cranial nerves, which presents with persistent unsteadiness of gait (particularly in darkness, during eye closure or under impaired visual conditions, or when standing/walking on uneven, soft or wobbly ground) and oscillopsia associated with head movements. The disease may be progressive, presenting no episodes of vertigo, or sequential, presenting recurrent episodes of vertigo. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Idiopathic bilateral vestibulopathy	c4545229	25,075	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=171684	2021-01-23T18:20:35	{"icd-10": ["H81.8"]}
Non-celiac gluten sensitivity Other namesGluten sensitivity SpecialtyGastroenterology, internal medicine, neurology[1] SymptomsIrritable bowel syndrome-like symptoms, fatigue, headache, fibromyalgia, atopic disorders, neurological diseases, psychiatric problems[2][3][4][5][6][7] Usual onsetAny age[8] Durationlifelong[9] CausesReaction to gluten, other proteins and FODMAPS from gluten-containing cereals[3][10] Diagnostic methodExclusion of celiac disease and wheat allergy, improvement with gluten withdrawal and worsening after gluten consumption[6][11][12] TreatmentGluten-free diet Frequency0.5%–13%[13] Non-celiac gluten sensitivity (NCGS) or gluten sensitivity[14] is defined as "a clinical entity induced by the ingestion of gluten leading to intestinal and/or extraintestinal symptoms that improve once the gluten-containing foodstuff is removed from the diet, and celiac disease and wheat allergy have been excluded".[15] NCGS is included in the spectrum of gluten-related disorders.[3][4] The definition and diagnostic criteria of non-celiac gluten sensitivity were debated and established by three consensus conferences.[4][14][15][16][17] The pathogenesis of NCGS is not yet well understood, but the activation of the innate immune system, the direct cytotoxic effects of gluten and probably other wheat components, are implicated.[3][18][19] There is evidence that not only gliadin (the main cytotoxic antigen of gluten), but also other proteins named ATIs which are present in gluten-containing cereals (wheat, rye, barley, and their derivatives) may have a role in the development of symptoms. ATIs are potent activators of the innate immune system.[3][20] FODMAPs, especially fructans, are present in small amounts in gluten-containing grains and have been identified as a possible cause of some gastrointestinal symptoms in NCGS patients.[3][10][21][20] As of 2019, reviews have concluded that although FODMAPs may play a role in NCGS, they explain only certain gastrointestinal symptoms, such as bloating, but not the extra-digestive symptoms that people with NCGS may develop, such as neurological disorders, fibromyalgia, psychological disturbances, and dermatitis.[20][9][3] For these reasons, NCGS is a controversial clinical condition[22] and some authors still question it.[23][24] It has been suggested that "non-celiac wheat sensitivity" is a more appropriate term, without forgetting that other gluten-containing cereals are implicated in the development of symptoms.[11][23] NCGS is the most common syndrome of gluten-related disorders[4][25] with prevalence rates between 0.5%–13% in the general population.[13] As no biomarker for diagnosing this condition is available, its diagnosis is made by exclusion of other gluten-related disorders, namely by excluding celiac disease and wheat allergy.[22] Many people have not been diagnosed following strict criteria and there is a "fad component" to the recent rise in popularity of the gluten-free diet, which leads to debate surrounding the evidence for this condition, its relationship to celiac disease and to irritable bowel syndrome.[3][5] People with non-celiac gluten sensitivity remain habitually in a "no man's land", without being recognized by the specialists and lacking the adequate medical care and treatment.[26] Most of these people have a long history of health complaints and unsuccessful consultations with numerous physicians, and this is the reason why many of them end up resorting to a gluten-free diet and a self-diagnosis of gluten sensitivity.[27] ## Contents * 1 Signs and symptoms * 1.1 Gastrointestinal * 1.2 Extraintestinal * 2 Causes * 2.1 Gluten * 2.2 Other proteins * 2.3 FODMAPs * 3 Diagnosis * 3.1 Differential diagnosis * 3.1.1 Celiac disease * 3.1.1.1 Serological markers * 3.1.1.2 Duodenal biopsies * 3.1.2 Wheat allergy * 3.2 Other tests * 3.3 People already on a gluten-free diet * 4 Treatment * 4.1 Persistent symptoms * 5 History * 6 Society and culture * 7 Research * 8 See also * 9 References ## Signs and symptoms[edit] Reported symptoms of NCGS are similar to those of celiac disease,[28][29] with most patients reporting both gastrointestinal and non-gastrointestinal symptoms.[27][30] In the "classical" presentation of NCGS, gastrointestinal symptoms are similar to those of irritable bowel syndrome, and are also not distinguishable from those of wheat allergy, but there is a different interval between exposure to wheat and onset of symptoms. Wheat allergy has a fast onset (from minutes to hours) after the consumption of food containing wheat and can be anaphylaxic.[30] ### Gastrointestinal[edit] Gastrointestinal symptoms may include any of the following: abdominal pain, bloating, bowel habit abnormalities (either diarrhea or constipation),[4][6] nausea, aerophagia, flatulence, gastroesophageal reflux disease, and aphthous stomatitis.[3][4][19] ### Extraintestinal[edit] NCGS can cause a wide range of extraintestinal symptoms, which can be the only manifestation of NCGS in absence of gastrointestinal symptoms.[3][4][6][5][7] These include any of the following: headache, migraine, "foggy mind", fatigue, fibromyalgia,[7][31] joint and muscle pain, leg or arm numbness, tingling of the extremities, dermatitis (eczema or skin rash), atopic disorders such as asthma, rhinitis, other allergies, depression, anxiety, iron-deficiency anemia, folate deficiency, or autoimmune diseases.[3][4][6][7] Play media A man with gluten ataxia: previous situation and evolution after three months of gluten-free diet NCGS is also linked to a wide spectrum of neurological and psychiatric disorders, including ataxia, schizophrenia, epilepsy, peripheral neuropathy, encephalopathy, vascular dementia, eating disorders, autism, attention deficit hyperactivity disorder (ADHD), hallucinations (so-called "gluten psychosis"), and various movement disorders (restless legs syndrome, chorea, parkinsonism, Tourette syndrome, palatal tremor, myoclonus, dystonia, opsoclonus myoclonus syndrome, paroxysms, dyskinesia, myorhythmia, myokymia).[1][32][2][3][4][5][6][7][33][34][35] Above 20% of people with NCGS have IgE-mediated allergy to one or more inhalants, foods, or metals, among which most common are mites, graminaceae, parietaria, cat or dog hair, shellfish, and nickel.[6] Approximately 35% of patients suffer other food intolerances, mainly lactose intolerance.[7] ## Causes[edit] The pathogenesis of NCGS is not yet well understood, but the activation of the innate immune system, the direct cytotoxic effects of gluten, and probably the cytotoxicity of other wheat molecules are implicated.[3][18][19] Besides gluten, other components in wheat, rye, barley, and their derivatives, including amylasetrypsin inhibitors (ATIs) and FODMAPs, may cause symptoms.[3] ### Gluten[edit] It was hypothesized that gluten, as occurs in celiac disease, is the cause of NCGS. In addition to its ability to elicit abnormal responses of the immune system, in vitro studies on cell cultures showed that gluten is cytotoxic and causes direct intestinal damage. Gluten and gliadin promote cell apoptosis (a form of programmed cell death) and reduce the synthesis of nucleic acids (DNA and RNA) and proteins, leading to a reduction in the viability of cells. Gluten alters cellular morphology and motility, cytoskeleton organization, oxidative balance and intercellular contact (tight junction proteins).[18][36] ### Other proteins[edit] Some people may have a reaction to other proteins (α-amylase/trypsin inhibitors [ATIs]) present in gluten-containing cereals that are able to inhibit amylase and trypsin.[3][37][20] They have been identified as the possible activator of the innate immune system in celiac disease and NCGS.[3][20] ATIs are part of the plant's natural defence against insects and may cause toll-like receptor 4 (TLR4)-mediated intestinal inflammation in humans.[20][38][39] These TLR4-stimulating activities of ATIs are limited to gluten-containing cereals (wheat, rye, barley, and derivatives) and may induce innate immunity in people with celiac disease or NCGS. ATIs resist proteolytic digestion.[3] ATIs are about 2%–4% of the total protein in modern wheat and are present in commercial gluten.[3] A 2017 study in mice demonstrated that ATIs exacerbate preexisting inflammation and may also worsen it at extraintestinal sites. This may explain why there is an increase of inflammation in people with preexisting diseases upon ingestion of ATI-containing grains.[20] Modern wheat cultivation, by breeding for high ATI content, may play a role in the onset and course of disorders such as celiac disease and gluten sensitivity.[40] However, it has been questioned whether there is sufficient empirical evidence to support this claim, because as of 2018 we lack studies that directly compare modern wheat versus ancient cultivars with low ATI content (such as einkorn wheat) in people with NCGS.[20][41] Wheat germ agglutinin is also considered to be a possible trigger of NCGS-like symptoms.[7] ### FODMAPs[edit] FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) that are present in gluten-containing grains (mainly fructans) have been identified as a possible cause of gastrointestinal symptoms in people with NCGS, in place of,[42] or in addition to, gluten.[10] The amount of fructans in gluten-containing cereals is relatively small and their role has been controversial. In rye they account for 3.6%–6.6% of dry matter, 0.7%–2.9% in wheat, and barley contains only trace amounts.[20] They are only minor sources of FODMAPs when eaten in the usual standard amounts in the daily diet.[3] Wheat and rye may comprise a major source of fructans when consumed in large amounts.[43] They may cause mild wheat intolerance at most, limited to certain gastrointestinal symptoms, such as bloating, but do not justify the NCGS extradigestive symptoms.[3] A 2018 review concluded that although fructan intolerance may play a role in NCGS, it only explains some gastrointestinal symptoms, but not the extradigestive symptoms that people with NCGS may develop, such as neurological disorders, fibromyalgia, psychological disturbances, and dermatitis. FODMAPs cause digestive symptoms when the person is hypersensitive to luminal distension.[20] A 2019 review concluded that wheat fructans can cause certain IBS-like symptoms, such as bloating, but are unlikely to cause immune activation or extra-digestive symptoms. Many people with NCGS report resolution of their symptoms after removing gluten-containing cereals while continue to eat fruits and vegetables with high FODMAPs content.[9] ## Diagnosis[edit] Absence of reliable biomarkers and the fact that some people do not have digestive symptoms make the recognition and diagnosis of non-celiac gluten sensitivity (NCGS) difficult.[37][1] Diagnosis is generally performed only by exclusion criteria.[13][22] NCGS diagnostic recommendations have been established by several consensus conferences. Exclusion of celiac disease and wheat allergy[6] is important because these two conditions also appear in people who experience symptoms similar to those of NCGS, which improve with a gluten withdrawal and worsen after gluten consumption.[6][11][12][33] The onset of NCGS symptoms may be delayed hours to a few days after gluten ingestion, whereas in celiac disease it can take days to weeks.[11] Wheat allergy has a fast onset (from minutes to hours) after the consumption of food containing wheat and can lead to anaphylaxis.[30] The presence of related extraintestinal manifestations has been suggested to be a feature of NCGS.[11] When symptoms are limited to gastrointestinal effects, there may be an overlap with wheat allergy, irritable bowel syndrome (IBS), and (less likely) intolerance to FODMAPs.[11] Proposed criteria for a diagnosis of NCGS suggest an improvement of gastrointestinal symptoms and extra-intestinal manifestations higher than 30% with a gluten-free diet (GFD), assessed through a rating scale, is needed to make a clinical diagnosis of NCGS.[33] To exclude a placebo effect, a double-blind placebo-controlled gluten challenge is a useful tool, although it is expensive and complicated for routine clinical use, and so is usually performed in research studies.[6][22] These suggestions were incorporated in the Salerno expert consensus on diagnostic criteria for NCGS. These recommend assessment of the response to a 6-week trial of a gluten-free diet using a defined rating scale (Step 1), followed by a double-blind, placebo-controlled challenge of gluten (or placebo) for a week of each (Step 2).[33] A variation of greater than 30% in the main symptoms when challenged by gluten or placebo is needed for a positive result. Further research on possible biomarkers was also identified.[33] ### Differential diagnosis[edit] Examinations evaluating celiac disease and wheat allergy must be performed before patients remove gluten from their diet.[6] It is critical to make a clear distinction between celiac disease and NCGS.[13] #### Celiac disease[edit] The main goal in diagnosing NCGS is to exclude celiac disease.[7][21] NCGS and celiac disease cannot be separated in diagnosis because many gastrointestinal and non-gastrointestinal symptoms are similar in both diseases,[21][27][28] and there are people with celiac disease having negative serology (absence of specific celiac disease antibodies in serum) or without villus atrophy.[13][44] There is no test capable of eliminating a diagnosis of a celiac disease,[45] but such a diagnosis is unlikely without confirming HLA-DQ2 and/or HLA-DQ8 haplotypes.[30] The prevalence of undiagnosed celiac disease increased 4-fold during the past half century[3] with most cases remaining unrecognized, undiagnosed and untreated, leaving celiac people with the risk of long-term complications.[37][46] Some people with NCGS may indeed have celiac disease.[13] A 2015 systematic review found that 20% of people with NCGS presenting with HLA-DQ2 and/or HLA-DQ8 haplotypes, negative serology, and normal histology or duodenal lymphocytosis had celiac disease.[13] The presence of autoimmune symptoms in people with NCGS suggests the possibility of undiagnosed celiac disease.[13] Autoimmune diseases typically associated with celiac disease are diabetes mellitus type 1, thyroiditis,[47] gluten ataxia, psoriasis, vitiligo, autoimmune hepatitis, dermatitis herpetiformis, primary sclerosing cholangitis, and others.[47] To evaluate the possible presence of celiac disease, specific serology and duodenal biopsies are required while the person is still on a diet that includes gluten.[3][37] ##### Serological markers[edit] Serological CD markers (IgA tissue transglutaminase [tTGA], IgA endomysial [EmA][6][37] and IgG deamidated gliadin peptide [DGP][6][13] antibodies) are always negative in those with NCGS;[6][12][21][37] in addition to specific IgA autoantibody levels, it is necessary to determine total IgA levels.[12][28] IgG tTGA antibodies should be checked in selective IgA deficiency, which can be associated with celiac disease and occurs in up to 1 in 40 celiac patients.[12] Nevertheless, the absence of serological markers does not certainly exclude celiac disease. In those with celiac disease before diagnosis (on a gluten-containing diet), celiac disease serological markers are not always present.[30] As the age of diagnosis increases, these antibody titers decrease, and may be low or even negative in older children and adults. The absence of celiac disease-specific antibodies is more common in patients without villous atrophy who only have duodenal lymphocytosis (Marsh 1 lesions) and who responds to a gluten-free diet with histological and symptomatic improvement.[13] ##### Duodenal biopsies[edit] According to the diagnostic criteria established by the consensus conferences (2011 and 2013), it is necessary to perform duodenal biopsies to exclude celiac disease in symptomatic people with negative specific celiac disease antibodies.[6] Due to the patchiness of the celiac disease lesions, four or more biopsies are taken from the second and third parts of the duodenum, and at least one from the duodenal bulb.[21][28] Even in the same biopsy fragments, different degrees of pathology may exist.[28] Duodenal biopsies in people with NCGS are always almost normal[7][12][21][28] – an essential parameter for diagnosis of NCGS,[28] although is generally accepted that a subgroup of people with NGCS may have an increased number of duodenal intraepithelial lymphocytes (IELs)[7][13][37] ( ≥25/100 enterocytes), which represent Marsh I lesions.[13] Nevertheless, Marsh I is considered compatible with celiac disease[21] and the most frequent cause of these findings, especially in people positive for HLA DQ2 and/or DQ8 haplotypes, is celiac disease,[7][13] with a prevalence of 16-43%.[13] In people with duodenal lymphocytosis – following guidelines from the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) – a high count of celiac disease cells (or CD/CD3 ratio) in immunohistochemical assessment of biopsies, or the presence of IgA anti-TG2[13][7] and/or anti-endomysial[7] intestinal deposits, might be specific markers for celiac disease.[7][13] Catassi and Fasano proposed in 2010 that in patients without celiac disease antibodies, either lymphocytic infiltration associated with IgA subepithelial deposits or a histological response to a gluten-free diet, could support a diagnosis of celiac disease.[13] #### Wheat allergy[edit] The clinical presentation may be sufficient in most cases to distinguish a wheat allergy from other entities.[28] It is excluded when there are normal levels of serum IgE antibodies to gluten proteins and wheat fractions, and no skin reaction to prick tests for wheat allergy.[6] Nevertheless, these tests are not always completely reliable.[11] If an allergic reaction can not be clearly identified, the diagnosis should be confirmed by food provocation tests, ideally performed in a double-blinded and placebo-controlled manner. Delayed allergic reactions may occur with these type of tests, which have to be negative over time, but there are no international consensus statements on diagnosing delayed wheat/food-related symptoms. Usually, reactions that appear between two hours and five days after the oral challenge are considered delayed.[21] Mucosal challenge followed by confocal endomicroscopy is a complementary diagnostic technique, but this technology is not yet generally available and remains experimental.[11] ### Other tests[edit] Evaluating the presence of antigliadin antibodies (AGA) can be a useful complementary diagnostic test. Up to 50% NCGS patients may have elevated AGA IgG antibodies, but rarely AGA IgA antibodies (only 7% of the cases).[6][7][37] In these patients, unlike in those with celiac disease, the IgG AGA became undetectable within 6 months of using a gluten-free diet.[6] ### People already on a gluten-free diet[edit] Many people remove gluten from the diet after a long history of health complaints and unsuccessful consultations with numerous physicians, who simply consider them to be suffering from irritable bowel syndrome, or even before seeking medical attention.[6][7][27][37] This fact can diminish the CD serological markers titers and may attenuate the inflammatory changes found in the duodenal biopsies.[7][37] In these cases, patients should be tested for the presence of HLA-DQ2/DQ8 genetic markers because a negative HLA-DQ2 and HLA-DQ8 result has a high negative predictive value for celiac disease.[6][7][37] If these markers are positive, it is advisable to undertake a gluten challenge under medical supervision, followed by serology and duodenal biopsies.[6][7][37] However, gluten challenge protocols have significant limitations, because a symptomatic relapse generally precedes the onset of a serological and histological relapse, and therefore becomes unacceptable for many patients.[6][7][21][37] Gluten challenge is also discouraged before the age of 5 years and during pubertal growth.[21] It remains unclear what daily intake of gluten is adequate and how long the gluten challenge should last.[37] Some protocols recommend eating a maximum of 10 g of gluten per day for 6 weeks. Nevertheless, recent studies have shown that a 2-week challenge of 3 g of gluten per day may induce histological and serological abnormalities in most adults with proven celiac disease.[7][37] This new proposed protocol has shown higher tolerability and compliance. It has been calculated that its application in secondary-care gastrointestinal practice would identify celiac disease in 7% of patients referred for suspected NCGS, while the remaining 93% would be confirmed as NCGS;[37] this is not yet universally adopted.[7] For people on a gluten-free diet who are unable to perform an oral gluten challenge, an alternative to identify possible celiac disease is an in vitro gliadin challenge of small bowel biopsies; this test is only available at selected specialized tertiary-care centers.[7] ## Treatment[edit] Main article: Gluten-free diet After exclusion of celiac disease and wheat allergy,[27] the subsequent step for diagnosis and treatment of NCGS is to start a strict gluten-free diet (GFD) to assess if symptoms improve or resolve completely. This may occur within days to weeks of starting a GFD, but improvement may also be due to a non-specific, placebo response.[48] The recovery of the nervous system is slow and sometimes incomplete.[35][49] Recommendations may resemble those for celiac disease, for the diet to be strict and maintained, with no transgression.[6] The degree of gluten cross contamination tolerated by people with NCGS is not clear but there is some evidence that they can present with symptoms even after consumption of small amounts.[6] Sporadic accidental contaminations with gluten can reactivate movement disorders.[35] A part of people with gluten-related neuropathy or ataxia appears not to be able to tolerate even the traces of gluten allowed in most foods labeled as "gluten-free".[49] Whereas celiac disease requires adherence to a strict lifelong gluten-free diet, it is not yet known whether NCGS is a permanent or a transient condition.[6][22] The results of a 2017 study suggest that NCGS may be a chronic disorder, as is the case with celiac disease.[9] A trial of gluten reintroduction to observe any reaction after 1–2 years of strict gluten-free diet might be performed.[6] A strict gluten-free diet is effective in most of the neurological disorders associated with NCGS, ameliorating or even resolving the symptoms. It should be started as soon as possible to improve the prognosis.[1] The death of neurons in the cerebellum in ataxia is the result of gluten exposure and is irreversible. Early treatment with a strict gluten-free diet can improve ataxia symptoms and prevent its progression.[32][50] When dementia has progressed to an advanced degree, the diet has no beneficial effect. Cortical myoclonus appears to be treatment-resistant on both gluten-free diet and immunosuppression.[1] ### Persistent symptoms[edit] Approximately one third of presumed NCGS patients continue to have symptoms, despite gluten withdrawal. Apart from a possible diagnostic error, there are multiple possible explanations.[6] One reason is poor compliance with gluten withdrawal, whether voluntary and/or involuntary.[6] There may be ingestion of gluten, in the form of cross contamination or food containing hidden sources.[10] In some cases, the amelioration of gastrointestinal symptoms with a gluten-free diet is only partial, and these patients could significantly improve with the addition of a low-FODMAP diet.[10] A subgroup may not improve when eating commercially available gluten-free products, as these can be rich in preservatives and additives such as sulfites, glutamates, nitrates and benzoates, which can also have a role in triggering functional gastrointestinal symptoms.[10] Furthermore, people with NCGS may often present with IgE-mediated allergies to one or more foods.[6] It has been estimated that around 35% suffer other food intolerances, mainly lactose intolerance.[7] ## History[edit] The subject of "food intolerance", including gluten sensitivity and elimination diets, was discussed in 1976.[51] Patients with symptoms including abdominal pain and diarrhea, which improved on gluten withdrawal, and who did not have celiac disease were initially described in 1976 and 1978 with the first series in 1980.[52][53][54] Debate regarding the existence of a specific condition has continued since then, but the three consensus conferences held since 2010 produced consistent definitions of NCGS and its diagnostic criteria.[4][14][16] ## Society and culture[edit] See also: Gluten-free diet NCGS has been a topic of popular interest.[55][56] Gluten has been named "the new diet villain".[57] The gluten-free diet has become popular in the United States and other countries.[3] Clinicians worldwide have been challenged by an increasing number of people who do not have celiac disease nor wheat allergy, with digestive or extra-digestive symptoms which improved after removing wheat / gluten from the diet. Many of these persons began a gluten-free diet on their own, without having been previously evaluated.[58][59] Another reason that contributed to this trend was the publication of several books that demonize gluten and point to it as a cause of type 2 diabetes, weight gain and obesity, and a broad list of conditions ranging from depression and anxiety to arthritis and autism.[60][61] The book that has had the most impact is Grain Brain: The Surprising Truth about Wheat, Carbs, and Sugar – Your Brain's Silent Killers, by the American neurologist David Perlmutter, published on September 2013.[60] Another book that has had great impact is Wheat Belly: Lose the Wheat, Lose the Weight, and Find Your Path Back to Health, by cardiologist William Davis.[61] The gluten-free diet has been advocated and followed by many celebrities to lose weight, such as Miley Cyrus and Gwyneth Paltrow, and some elite athletes to improve performance.[62][63] Estimates suggest that in 2014, 30% of people in the US and Australia were consuming gluten-free foods, with estimates that by 2016 approximately 100 million Americans would consume gluten-free products.[3][60][64] Data from a 2015 Nielsen survey of 30,000 adults in 60 countries around the world showed that 21% of people prefer to buy gluten-free foods, with interest highest among younger generations.[65] Another school of thought suggests that many people may be unnecessarily avoiding gluten when they do not need to.[24][66][67] Debate around NCGS as a genuine clinical condition can be heightened because often patients are self diagnosed, or a diagnosis is made by alternative health practitioners.[5] Many people who are making a gluten-free diet did not previously exclude celiac disease or, when they are fully evaluated, other alternative diagnoses can be found such as fructose intolerance or small intestinal bacterial overgrowth, or a better response to a low-FODMAP diet obtained.[7][6][59] ## Research[edit] There are many open questions on gluten sensitivity,[10] emphasized in one review that "it is still to be clarified whether this disorder is permanent or transient and whether it is linked to autoimmunity".[68] It has not yet been established whether innate or adaptive immune responses are involved in NCGS, nor whether the condition relates specifically to gluten or rather relates to other components of grains.[29][69] Studies indicate that AGA IgG is high in slightly more than half of NCGS patients[4] and that, unlike for celiac disease patients, the IgG AGA decreases strongly over 6 months of gluten-free diet; AGA IgA is usually low or absent in NCGS patients.[4][70] The need for developing biomarkers for NCGS is frequently emphasized;[4][27][71] for example, one review indicated: "There is a desperate need for reliable biomarkers ... that include clinical, biochemical and histopathological findings which support the diagnosis of NCGS."[29] Research has also attempted to discern, by double-blind placebo-controlled trials, between a "fad component" to the recent popularity of the gluten-free diet and an actual sensitivity to gluten or other components of wheat.[3][4][72] In a 2013 double-blind, placebo-controlled challenge (DBPC) by Biesiekierski et al. in a few people with IBS, the authors found no difference between gluten or placebo groups and the concept of NCGS as a syndrome was questioned. Nevertheless, this study had design errors and an incorrect selection of participants, and probably the reintroduction of both gluten and whey protein had a nocebo effect similar in all people, and this could have masked the true effect of gluten/wheat reintroduction.[7][37] In a 2015 double-blind placebo cross-over trial, small amounts of purified wheat gluten triggered gastrointestinal symptoms (such as abdominal bloating and pain) and extra-intestinal manifestations (such as foggy mind, depression and aphthous stomatitis) in self-reported NCGS. Nevertheless, it remains elusive whether these findings specifically implicate gluten or proteins present in gluten-containing cereals.[7] In a 2018 double-blind, crossover research study on 59 persons on a gluten-free diet with challenges of gluten, fructans or placebo, intestinal symptoms (specifically bloating) were borderline significantly higher after challenge with fructans, in comparison with gluten proteins (P = 0.049).[20][9] Although the differences between the three interventions was very small, the authors concluded that fructans (the specific type of FODMAP found in wheat) are more likely to be the cause of NCGS gastrointestinal symptoms, rather than gluten.[20] In addition, fructans used in the study were extracted from chicory root, so it remains to be seen whether the wheat fructans produce the same effect.[9] ## See also[edit] * Gluten-related disorders ## References[edit] 1. ^ a b c d e Zis P, Hadjivassiliou M (26 February 2019). "Treatment of Neurological Manifestations of Gluten Sensitivity and Coeliac Disease". Curr Treat Options Neurol (Review). 21 (3): 10. doi:10.1007/s11940-019-0552-7. PMID 30806821. S2CID 73466457. 2. ^ a b Catassi C (2015). "Gluten Sensitivity". Ann Nutr Metab (Review). 67 Suppl 2 (2): 16–26. doi:10.1159/000440990. PMID 26605537. 3. ^ 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 Fasano A, Sapone A, Zevallos V, Schuppan D (May 2015). "Nonceliac gluten sensitivity". Gastroenterology (Review). 148 (6): 1195–204. doi:10.1053/j.gastro.2014.12.049. PMID 25583468. "Cereals such as wheat and rye, when consumed in normal quantities, are only minor sources of FODMAPs in the daily diet. (...) Table 1. Sources of FODMAPs (...) Oligosaccharides (fructans and/or galactans). Cereals: wheat and rye when eaten in large amounts (eg, bread, pasta, couscous, crackers, biscuits)" 4. ^ a b c d e f g h i j k l m n Catassi C, Bai J, Bonaz B, Bouma G, Calabrò A, Carroccio A, Castillejo G, Ciacci C, Cristofori F, Dolinsek J, Francavilla R, Elli L, Green P, Holtmeier W, Koehler P, Koletzko S, Meinhold C, Sanders D, Schumann M, Schuppan D, Ullrich R, Vécsei A, Volta U, Zevallos V, Sapone A, Fasano A (2013). "Non-celiac gluten sensitivity: the new frontier of gluten related disorders". Nutrients (Review). 5 (10): 3839–3853. doi:10.3390/nu5103839. ISSN 2072-6643. PMC 3820047. PMID 24077239. "Gluten sensitivity (GS) was originally described in the 1980s [1] and a recently “re-discovered” syndrome entity, characterized by intestinal and extraintestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected with either celiac disease (CD) or wheat allergy (WA)." 5. ^ a b c d e Lebwohl B, Ludvigsson JF, Green PH (Oct 2015). "Celiac disease and non-celiac gluten sensitivity". BMJ (Review). 351: h4347. doi:10.1136/bmj.h4347. PMC 4596973. PMID 26438584. 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 Volta U, Caio G, De Giorgio R, Henriksen C, Skodje G, Lundin KE (Jun 2015). "Non-celiac gluten sensitivity: a work-in-progress entity in the spectrum of wheat-related disorders". Best Pract Res Clin Gastroenterol (Review). 29 (3): 477–91. doi:10.1016/j.bpg.2015.04.006. PMID 26060112. 7. ^ 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 Aziz I, Hadjivassiliou M, Sanders DS (Sep 2015). "The spectrum of noncoeliac gluten sensitivity". Nat Rev Gastroenterol Hepatol (Review). 12 (9): 516–26. doi:10.1038/nrgastro.2015.107. PMID 26122473. S2CID 2867448. 8. ^ Watkins RD, Zawahir S (2017). "Celiac Disease and Nonceliac Gluten Sensitivity". Pediatr Clin North Am (Review). 64 (3): 563–576. doi:10.1016/j.pcl.2017.01.013. PMID 28502438. 9. ^ a b c d e f Volta U, De Giorgio R, Caio G, Uhde M, Manfredini R, Alaedini A (2019). "Nonceliac Wheat Sensitivity: An Immune-Mediated Condition with Systemic Manifestations". Gastroenterol Clin North Am (Review). 48 (1): 165–182. doi:10.1016/j.gtc.2018.09.012. PMC 6364564. PMID 30711208. 10. ^ a b c d e f g Volta U, Caio G, Tovoli F, De Giorgio R (2013). "Non-celiac gluten sensitivity: questions still to be answered despite increasing awareness". Cellular and Molecular Immunology (Review). 10 (5): 383–392. doi:10.1038/cmi.2013.28. ISSN 1672-7681. PMC 4003198. PMID 23934026. 11. ^ a b c d e f g h Schuppan D, Pickert G, Ashfaq-Khan M, Zevallos V (Jun 2015). "Non-celiac wheat sensitivity: differential diagnosis, triggers and implications". Best Pract Res Clin Gastroenterol (Review). 29 (3): 469–76. doi:10.1016/j.bpg.2015.04.002. PMID 26060111. 12. ^ a b c d e f Green PH, Lebwohl B, Greywoode R (May 2015). "Celiac disease". J Allergy Clin Immunol. 135 (5): 1099–106. doi:10.1016/j.jaci.2015.01.044. PMID 25956012. 13. ^ a b c d e f g h i j k l m n o p q Molina-Infante J, Santolaria S, Sanders DS, Fernández-Bañares F (May 2015). "Systematic review: noncoeliac gluten sensitivity". Aliment Pharmacol Ther (Review). 41 (9): 807–20. doi:10.1111/apt.13155. PMID 25753138. 14. ^ a b c Ludvigsson JF, Leffler DA, Bai JC, Biagi F, Fasano A, Green PH, Hadjivassiliou M, Kaukinen K, Kelly CP, Leonard JN, Lundin KE, Murray JA, Sanders DS, Walker MM, Zingone F, Ciacci C (January 2013). "The Oslo definitions for coeliac disease and related terms". Gut (Consensus Development Conference. Research Support, N.I.H., Extramural. Research Support, Non-U.S. Gov't). 62 (1): 43–52. doi:10.1136/gutjnl-2011-301346. PMC 3440559. PMID 22345659. 15. ^ a b Fasano A, Sapone A, Zevallos V, Schuppan D (May 2015). "Nonceliac gluten sensitivity". Gastroenterology (Review). 148 (6): 1195–204. doi:10.1053/j.gastro.2014.12.049. PMID 25583468. "Since 2010, the definition of NCGS has been discussed at 3 consensus conferences, which led to 3 publications. Given the uncertainties about this clinical entity and the lack of diagnostic biomarkers, all 3 reports concluded that NCGS should be defined by the following exclusionary criteria: a clinical entity induced by the ingestion of gluten leading to intestinal and/or extraintestinal symptoms that resolve once the gluten-containing foodstuff is eliminated from the diet, and when celiac disease and wheat allergy have been ruled out." 16. ^ a b Sapone A, Bai JC, Ciacci C, Dolinsek J, Green PH, Hadjivassiliou M, Kaukinen K, Rostami K, Sanders DS, Schumann M, Ullrich R, Villalta D, Volta U, Catassi C, Fasano A (2012). "Spectrum of gluten-related disorders: consensus on new nomenclature and classification". BMC Medicine (Review). 10: 13. doi:10.1186/1741-7015-10-13. PMC 3292448. PMID 22313950. 17. ^ Volta U, Caio G, De Giorgio R, Henriksen C, Skodje G, Lundin KE (Jun 2015). "Non-celiac gluten sensitivity: a work-in-progress entity in the spectrum of wheat-related disorders". Best Pract Res Clin Gastroenterol (Review). 29 (3): 477–91. doi:10.1016/j.bpg.2015.04.006. PMID 26060112. "According to the diagnostic criteria established by two Consensus Conferences (London 2011 and Munich 2012), the current view to NCGS diagnosis is based on symptom / manifestation evaluation along with the exclusion of CD and WA [5,7]." 18. ^ a b c Elli L, Roncoroni L, Bardella MT (2015). "Non-celiac gluten sensitivity: Time for sifting the grain". World J Gastroenterol (Review). 21 (27): 8221–6. doi:10.3748/wjg.v21.i27.8221. PMC 4507091. PMID 26217073.CS1 maint: multiple names: authors list (link) 19. ^ a b c Leonard MM, Sapone A, Catassi C, Fasano A (2017). "Celiac Disease and Nonceliac Gluten Sensitivity: A Review". JAMA (Review). 318 (7): 647–656. doi:10.1001/jama.2017.9730. PMID 28810029. S2CID 205094729. "Previous studies have shown that gliadin can cause an immediate and transient increase in gut permeability. This permeating effect is secondary to the binding of specific undigestible gliadin fragments to the CXCR3 chemokine receptor with subsequent release of zonulin, a modulator of intercellular tight junctions. This process takes place in all individuals who ingest gluten." 20. ^ a b c d e f g h i j k l Verbeke, K (February 2018). "Nonceliac Gluten Sensitivity: What Is the Culprit?". Gastroenterology. 154 (3): 471–473. doi:10.1053/j.gastro.2018.01.013. PMID 29337156. 21. ^ a b c d e f g h i j Ontiveros N, Hardy MY, Cabrera-Chavez F (2015). "Assessing of Celiac Disease and Nonceliac Gluten Sensitivity". Gastroenterology Research and Practice (Review). 2015: 1–13. doi:10.1155/2015/723954. PMC 4429206. PMID 26064097. 22. ^ a b c d e Vriezinga SL, Schweizer JJ, Koning F, Mearin ML (Sep 2015). "Coeliac disease and gluten-related disorders in childhood". Nat Rev Gastroenterol Hepatol (Review). 12 (9): 527–36. doi:10.1038/nrgastro.2015.98. PMID 26100369. S2CID 2023530. "NCGS is a clinical condition in which intestinal and extraintestinal symptoms are triggered by gluten ingestion, in the absence of coeliac disease and wheat allergy. The symptoms usually occur soon after gluten ingestion, improve or disappear within hours or a few days after gluten withdrawal, and relapse following its reintroduction. ... Unlike coeliac disease and wheat allergy, NCGS is an unclear and controversial entity." 23. ^ a b Fasano A, Sapone A, Zevallos V, Schuppan D (May 2015). "Nonceliac gluten sensitivity". Gastroenterology (Review). 148 (6): 1195–204. doi:10.1053/j.gastro.2014.12.049. PMID 25583468. "One of the most controversial and highly debated discussions concerns the role of gluten in causing NCGS. Recent reports have indicated that gluten might not be the cause of NCGS, and some investigators still question whether NCGS as a real clinical entity. (...) Cereals such as wheat and rye, when consumed in normal quantities, are only minor sources of FODMAPs in the daily diet (Table 1). Therefore, gluten-containing grains are not likely to induce IBS exclusively via FODMAPs. In contrast, there is growing evidence that other proteins that are unique to gluten-containing cereals can elicit an innate immune response that leads to NCGS, raising a nomenclature issue. For this reason, wheat sensitivity, rather than gluten sensitivity, seems to be a more appropriate term, keeping in mind that other gluten-containing grains such as barley and rye also can trigger the symptoms." 24. ^ a b Makharia A, Catassi C, Makharia GK (2015). "The Overlap between Irritable Bowel Syndrome and Non-Celiac Gluten Sensitivity: A Clinical Dilemma". Nutrients. 7 (12): 10417–26. doi:10.3390/nu7125541. PMC 4690093. PMID 26690475. 25. ^ Czaja-Bulsa G (Apr 2015). "Non coeliac gluten sensitivity – A new disease with gluten intolerance". Clin Nutr (Review). 34 (2): 189–94. doi:10.1016/j.clnu.2014.08.012. PMID 25245857. "The new syndrome has been named non-celiac gluten sensitivity (NCGS) or gluten sensitivity (GS)." 26. ^ Verdu EF, Armstrong D, Murray JA (2009). "Between celiac disease and irritable bowel syndrome: the "no man's land" of gluten sensitivity". Am J Gastroenterol (Review). 104 (6): 1587–94. doi:10.1038/ajg.2009.188. PMC 3480312. PMID 19455131. 27. ^ a b c d e f Mansueto, Pasquale; Seidita, Aurelio; D'Alcamo, Alberto; Carroccio, Antonio (2014). "Non-Celiac Gluten Sensitivity: Literature Review" (PDF). Journal of the American College of Nutrition (Review). 33 (1): 39–54. doi:10.1080/07315724.2014.869996. hdl:10447/90208. ISSN 0731-5724. PMID 24533607. 28. ^ a b c d e f g h Tonutti E, Bizzaro N (2014). "Diagnosis and classification of celiac disease and gluten sensitivity". Autoimmun Rev (Review). 13 (4–5): 472–6. doi:10.1016/j.autrev.2014.01.043. PMID 24440147. 29. ^ a b c Nijeboer P, Bontkes HJ, Mulder CJ, Bouma G (December 2013). "Non-celiac gluten sensitivity. Is it in the gluten or the grain?". Journal of Gastrointestinal and Liver Diseases (Review). 22 (4): 435–40. PMID 24369326. 30. ^ a b c d e Fasano, A; Catassi, C (Dec 20, 2012). "Clinical practice. Celiac disease". The New England Journal of Medicine (Review). 367 (25): 2419–26. doi:10.1056/NEJMcp1113994. PMID 23252527. 31. ^ Rossi A, Di Lollo AC, Guzzo MP, Giacomelli C, Atzeni F, Bazzichi L, Di Franco M (2015). "Fibromyalgia and nutrition: what news?". Clin Exp Rheumatol (Review). 33 (1 Suppl 88): S117–25. PMID 25786053. 32. ^ a b Mitoma H, Adhikari K, Aeschlimann D, Chattopadhyay P, Hadjivassiliou M, Hampe CS, et al. (2016). "Consensus Paper: Neuroimmune Mechanisms of Cerebellar Ataxias". Cerebellum (Review). 15 (2): 213–32. doi:10.1007/s12311-015-0664-x. PMC 4591117. PMID 25823827. 33. ^ a b c d e Catassi, C; Elli, L; Bonaz, B; Bouma, G; Carroccio, A; Castillejo, G; Cellier, C; Cristofori, F; De Magistris, L; Dolinsek, J; Dieterich, W; Francavilla, R; Hadjivassiliou, M; Holtmeier, W; Körner, U; Leffler, D. A.; Lundin, K. E.; Mazzarella, G; Mulder, C. J.; Pellegrini, N; Rostami, K; Sanders, D; Skodje, G. I.; Schuppan, D; Ullrich, R; Volta, U; Williams, M; Zevallos, V. F.; Zopf, Y; Fasano, A (2015). "Diagnosis of Non-Celiac Gluten Sensitivity (NCGS): The Salerno Experts' Criteria". Nutrients. 7 (6): 4966–4977. doi:10.3390/nu7064966. PMC 4488826. PMID 26096570. 34. ^ Bressan, Paola; Kramer, Peter (2016). "Bread and Other Edible Agents of Mental Disease". Frontiers in Human Neuroscience. 10: 130. doi:10.3389/fnhum.2016.00130. ISSN 1662-5161. PMC 4809873. PMID 27065833. 35. ^ a b c Vinagre-Aragón A, Zis P, Grunewald RA, Hadjivassiliou M (2018). "Movement Disorders Related to Gluten Sensitivity: A Systematic Review". Nutrients (Systematic Review). 10 (8): 1034. doi:10.3390/nu10081034. PMC 6115931. PMID 30096784. 36. ^ Fasano A (Jan 2011). "Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer". Physiol. Rev. (Review). 91 (1): 151–75. CiteSeerX 10.1.1.653.3967. doi:10.1152/physrev.00003.2008. PMID 21248165. 37. ^ a b c d e f g h i j k l m n o p q Elli L, Branchi F, Tomba C, Villalta D, Norsa L, Ferretti F, Roncoroni L, Bardella MT (Jun 2015). "Diagnosis of gluten related disorders: Celiac disease, wheat allergy and non-celiac gluten sensitivity". World J Gastroenterol. 21 (23): 7110–9. doi:10.3748/wjg.v21.i23.7110. PMC 4476872. PMID 26109797. 38. ^ Barone, Maria; Troncone, Riccardo; Auricchio, Salvatore (2014). "Gliadin Peptides as Triggers of the Proliferative and Stress/Innate Immune Response of the Celiac Small Intestinal Mucosa". International Journal of Molecular Sciences (Review). 15 (11): 20518–20537. doi:10.3390/ijms151120518. ISSN 1422-0067. PMC 4264181. PMID 25387079. 39. ^ Junker, Y.; Zeissig, S.; Kim, S.-J.; Barisani, D.; Wieser, H.; Leffler, D. A.; Zevallos, V.; Libermann, T. A.; Dillon, S.; Freitag, T. L.; Kelly, C. P.; Schuppan, D. (2012). "Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4". Journal of Experimental Medicine. 209 (13): 2395–2408. doi:10.1084/jem.20102660. ISSN 0022-1007. PMC 3526354. PMID 23209313. 40. ^ Junker, Y.; Zeissig, S.; Kim, S.-J.; Barisani, D.; Wieser, H.; Leffler, D. A.; Zevallos, V.; Libermann, T. A.; Dillon, S.; Freitag, T. L.; Kelly, C. P.; Schuppan, D. (2012). "Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4". Journal of Experimental Medicine. 209 (13): 2395–2408. doi:10.1084/jem.20102660. ISSN 0022-1007. PMC 3526354. PMID 23209313. "more recent breeding of high yielding and highly pest-resistant wheat […] has led to a drastic increase of ATI content. […] Our finding of ATI as a potent stimulator of TLR4 in the intestine might not only be relevant to celiac disease, but is likely to have implications for patients with so-called gluten sensitivity and possibly for patients with irritable bowel syndrome, inflammatory bowel disease, and even nonintestinal inflammation." 41. ^ Kucek, Lisa Kissing; Veenstra, Lynn D.; Amnuaycheewa, Plaimein; Sorrells, Mark E. (2015). "A Grounded Guide to Gluten: How Modern Genotypes and Processing Impact Wheat Sensitivity". Comprehensive Reviews in Food Science and Food Safety. 14 (3): 285–302. doi:10.1111/1541-4337.12129. ISSN 1541-4337. 42. ^ Ontiveros N, Hardy MY, Cabrera-Chavez F (2015). "Assessing of Celiac Disease and Nonceliac Gluten Sensitivity". Gastroenterology Research and Practice (Review). 2015: 1–13. doi:10.1155/2015/723954. PMC 4429206. PMID 26064097. "The literature suggests that FODMAPs and not gluten per se are the triggers of gastrointestinal symptoms in patients that fit most of the proposed NCGS definitions" 43. ^ Gibson PR, Shepherd SJ (February 2010). "Evidence-based dietary management of functional gastrointestinal symptoms: The FODMAP approach". Journal of Gastroenterology and Hepatology. 25 (2): 252–8. doi:10.1111/j.1440-1746.2009.06149.x. PMID 20136989. "Wheat is a major source of fructans in the diet. (...) Table 1 Food sources of FODMAPs. (...) Oligosaccharides (fructans and/or galactans). Cereals: wheat & rye when eaten in large amounts (e.g. bread, pasta, couscous, crackers, biscuits)" 44. ^ Caio, Giacomo; Volta, Umberto; Sapone, Anna; Leffler, Daniel A.; De Giorgio, Roberto; Catassi, Carlo; Fasano, Alessio (2019-07-23). "Celiac disease: a comprehensive current review". BMC Medicine. 17 (1): 142. doi:10.1186/s12916-019-1380-z. ISSN 1741-7015. PMC 6647104. PMID 31331324. 45. ^ Rodrigo L, Garrote JA, Vivas S (Sep 6, 2008). "[Celiac disease] [Article in Spanish]". Med Clin (Barc). 131 (7): 264–70. doi:10.1016/S0025-7753(08)72247-4. PMID 18775218. 46. ^ Fasano A (Apr 2005). "Clinical presentation of celiac disease in the pediatric population". Gastroenterology. 128 (4 Suppl 1): S68–73. doi:10.1053/j.gastro.2005.02.015. PMID 15825129. 47. ^ a b Lundin KE, Wijmenga C (Sep 2015). "Coeliac disease and autoimmune disease-genetic overlap and screening". Nat Rev Gastroenterol Hepatol. 12 (9): 507–15. doi:10.1038/nrgastro.2015.136. PMID 26303674. S2CID 24533103. 48. ^ Genuis SJ, Lobo RA (2014). "Gluten Sensitivity Presenting as a Neuropsychiatric Disorder". Gastroenterology Research and Practice (Review). 2014: 1–6. doi:10.1155/2014/293206. ISSN 1687-6121. PMC 3944951. PMID 24693281. 49. ^ a b Hadjivassiliou M, Grünewald RA, Davies-Jones GA (2002). "Gluten sensitivity as a neurological illness". J Neurol Neurosurg Psychiatry (Review). 72 (5): 560–3. doi:10.1136/jnnp.72.5.560. PMC 1737870. PMID 11971034. 50. ^ Hadjivassiliou M, Sanders DD, Aeschlimann DP (2015). "Gluten-related disorders: gluten ataxia". Dig Dis (Review). 33 (2): 264–8. doi:10.1159/000369509. PMID 25925933. S2CID 207673823. 51. ^ Richard Mackarness (January, 1976), Not All in the Mind, Macmillan, ISBN 978-0330245920 52. ^ Cooper BT, Holmes GK, Ferguson R, Thompson RA, Cooke WT (1976). "Proceeding: Chronic diarrhoea and gluten sensitivity". Gut. 17 (5): 385–402. doi:10.1136/gut.17.5.385. PMID 1278762. "On clinical and biopsy evidence, these patients are sensitive to gluten; therefore making a definition of coeliac disease even more difficult" 53. ^ Ellis A, Linaker BD (1978). "Non-coeliac gluten sensitivity?". Lancet. 1 (8078): 1358–9. doi:10.1016/s0140-6736(78)92427-3. PMID 78118. 54. ^ Cooper BT, Holmes GK, Ferguson R, Thompson RA, Allan RN, Cooke WT (1980). "Gluten-sensitive diarrhea without evidence of celiac disease". Gastroenterology. 79 (5 Pt 1): 801–6. doi:10.1016/0016-5085(80)90432-1. PMID 7419003. 55. ^ Scott, Cameron. "Is non-celiac gluten sensitivity a real thing?". Healthline. Retrieved 9 April 2016. 56. ^ Reinagel, Monica. "Is non-celiac gluten sensitivity for real?". Scientific American. Retrieved 9 April 2016. 57. ^ Springen, Karen. "Are gluten-free diets healthier, or is it hype?". Newsweek. Retrieved 9 April 2016. 58. ^ Volta U, Caio G, Karunaratne TB, Alaedini A, De Giorgio R (2017). "Non-coeliac gluten/wheat sensitivity: advances in knowledge and relevant questions". Expert Rev Gastroenterol Hepatol (Review). 11 (1): 9–18. doi:10.1080/17474124.2017.1260003. PMID 27852116. S2CID 34881689. 59. ^ a b Lebwohl B, Ludvigsson JF, Green PH (Oct 2015). "Celiac disease and non-celiac gluten sensitivity". BMJ (Review). 5: 351:h4347. doi:10.1136/bmj.h4347. PMC 4596973. PMID 26438584. 60. ^ a b c Nash DT, Slutzky AR (2014). "Gluten sensitivity: new epidemic or new myth?". Proc (Bayl Univ Med Cent). 27 (4): 377–8. doi:10.1080/08998280.2014.11929164. PMC 4255872. PMID 25484517. 61. ^ a b Shewry PR, Hey SJ (2016). "Do we need to worry about eating wheat?". Nutr Bull. 41 (1): 6–13. doi:10.1111/nbu.12186. PMC 4760426. PMID 26941586. 62. ^ Jones AL (2017). "The Gluten-Free Diet: Fad or Necessity?". Diabetes Spectr. 30 (2): 118–123. doi:10.2337/ds16-0022. PMC 5439366. PMID 28588378. 63. ^ "Is gluten-free a lifestyle or a diet craze?". USA Today. 5 March 2013. Retrieved 4 April 2018. 64. ^ "An increasing number of Australians are choosing a gluten-free diet". Herald Sun. 18 November 2014. Retrieved 4 April 2018. 65. ^ Reilly NR (2016). "The Gluten-Free Diet: Recognizing Fact, Fiction, and Fad". J Pediatr. 175: 206–10. doi:10.1016/j.jpeds.2016.04.014. PMID 27185419. 66. ^ Zaraska, Marta. "For many, gluten isn't the villain it gets cracked up to be". Washington Post. Retrieved 9 April 2016. 67. ^ "Fad or fact -- gluten-free?". Core health. Retrieved 9 April 2016. 68. ^ Volta U, De Giorgio R (2012). "New understanding of gluten sensitivity". Nature Reviews Gastroenterology & Hepatology (Review). 9 (5): 295–299. doi:10.1038/nrgastro.2012.15. ISSN 1759-5045. PMID 22371218. S2CID 205487297. 69. ^ Biesiekierski JR, Muir JG, Gibson PR (2013). "Is gluten a cause of gastrointestinal symptoms in people without celiac disease?". Current Allergy and Asthma Reports (Review). 13 (6): 631–8. doi:10.1007/s11882-013-0386-4. PMID 24026574. S2CID 41014087. 70. ^ Caio G, Volta U, Tovoli F, De Giorgio R (2014). "Effect of gluten free diet on immune response to gliadin in patients with non-celiac gluten sensitivity". BMC Gastroenterology (Research Support, Non-U.S. Gov't). 14 (1): 26. doi:10.1186/1471-230X-14-26. ISSN 1471-230X. PMC 3926852. PMID 24524388. 71. ^ Branchi F, Aziz I, Conte D, Sanders DS (2015). "Noncoeliac gluten sensitivity: a diagnostic dilemma". Current Opinion in Clinical Nutrition and Metabolic Care (Review). 18 (5): 508–14. doi:10.1097/MCO.0000000000000207. PMID 26147528. S2CID 22402914. 72. ^ Di Sabatino A, Volta U, Salvatore C, Biancheri P, Caio G, De Giorgio R, Di Stefano M, Corazza GR (2015). "Small Amounts of Gluten in Subjects with Suspected Nonceliac Gluten Sensitivity: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Trial". Clinical Gastroenterology and Hepatology. 13 (9): 1604–12. doi:10.1016/j.cgh.2015.01.029. PMID 25701700. * v * t * e Gluten sensitivity Conditions general * Wheat allergy * Oat sensitivity nervous system * GS idiopathic neuropathies digestive system * Coeliac disease * GSE associated conditions integumentary system * Dermatitis herpetiformis Antibodies * Anti-gliadin antibodies * Anti-transglutaminase antibodies HLA-DQ * HLA-DQ2 * HLA-DQ8 Other * Gluten immunochemistry * Gluten-free diet * Gluten challenge test * List of people diagnosed with coeliac disease [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Non-celiac gluten sensitivity	c2711053	25,076	wikipedia	https://en.wikipedia.org/wiki/Non-celiac_gluten_sensitivity	2021-01-18T19:08:58	{"icd-10": ["K90.41"], "wikidata": ["Q19772377"]}
A number sign (#) is used with this entry because of evidence that Cornelia de Lange syndrome-2 (CDLS2) is caused by mutation in the SMC1A gene (300040), which encodes a subunit of the cohesin complex, on chromosome Xp11. Description Cornelia de Lange syndrome is a clinically heterogeneous developmental disorder characterized by malformations affecting multiple systems. Affected individuals have dysmorphic facial features, cleft palate, distal limb defects, growth retardation, and developmental delay. About 4 to 6% of patients have mutations in the X-linked SMC1A gene, whereas about 60% have mutations in the NIPBL gene (608667) on chromosome 5p13 (CDLS1; 122470) (summary by Musio et al., 2006, Hoppman-Chaney et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of Cornelia de Lange syndrome, see 122470. Clinical Features Musio et al. (2006) reported 4 affected males with SMC1A mutations and similar CDLS symptoms: typical facial dysmorphisms, mental retardation in the moderate to severe range, and growth deficits with feeding problems in childhood. Their hands were not malformed, but the size of their hands was under the third percentile. Shortness of the first ray, clinodactyly of the fifth finger, and incomplete movement of the elbow were also evident. Three of the patients were related (2 sibs and their cousin). The sporadic patient and 1 of the related males showed severe gastroesophageal reflux. Three out of the 4 affected males had similar cerebral abnormalities on CT scan, with dilatation of cerebral ventricles and enlarged cisterna magna. The sporadic patient had severe epilepsy, and the 3 related males were subject to febrile seizures with abnormal electroencephalogram. The mother of the 2 affected sibs showed a very mild clinical phenotype and a slight impairment in cognitive development. Typical facial dysmorphism was very slight, and there was no record of growth problems or major malformations. Limongelli et al. (2010) reported a 6-year-old girl with CDLS2 confirmed by genetic analysis (300040.0005). At birth and in infancy, she showed intrauterine growth retardation, developmental delay, and recurrent respiratory infections. Examination at age 6 years showed poor growth, microcephaly, synophrys, downslanting palpebral fissures, long and curly eyelashes, and thin vermilion of the upper lip. Echocardiography showed severe, concentric ventricular hypertrophy, with left ventricular outflow tract obstruction, mild aortic regurgitation, and mitral valve prolapse with mild mitral regurgitation. Hoppman-Chaney et al. (2012) reported a 10-year-old girl with CDLS2. She presented at age 7 months with developmental delay and multiple congenital anomalies including hemihypertrophy of the right side and tetralogy of Fallot. She had very poor growth, with low weight and height, and microcephaly. Craniofacial features included marked microbrachycephaly, skull asymmetry with right-sided flattening, prominent metopic suture, and bitemporal narrowing. She had sparse hair, deep-set eyes, arched eyebrows, mild synophrys, slightly anteriorly rotated ears with long and narrow earlobes, full cheeks, smooth philtrum, small mandible, widely spaced teeth, esotropia, and mild coloboma of both upper lids. Other features included short neck, broad thorax with widely spaced nipples, scoliosis, and mild distal limb anomalies. She had profound developmental delay with inability to sit without support, spasticity, and lack of speech. Brain MRI at age 13 months showed dysgenesis of the corpus callosum and semilobar holoprosencephaly. A G-banded chromosome study at birth showed mosaic Turner syndrome: 45,X(7)/46,XX(23). In addition, array CGH performed later showed a de novo 8-kb deletion encompassing exon 13 to intron 16 of the SMC1A gene (300040.0006), resulting in an in-frame deletion of 126 amino acids and insertion of 3 novel amino acids. The mutant mRNA was expressed, and Hoppman-Chaney et al. (2012) concluded that the mutant protein lacking the coiled-coil domain would act in a dominant-negative manner. Inheritance Most CDLS2 patients with SMC1A mutations are female. The SMC1A gene usually escapes X-inactivation in females, suggesting that heterozygous mutations exert a dominant-negative effect in manifesting female carriers. However, females with mutations in SMC1A typically have a milder phenotype compared to those with NIPBL mutations, particularly with respect to limb reduction defects. Males with SMC1A mutations show a more severe phenotype than females with SMC1A mutations (summary by Hoppman-Chaney et al., 2012). Molecular Genetics Musio et al. (2006) recruited 53 unrelated and 4 related individuals with a diagnosis of Cornelia de Lange syndrome, encompassing the entire spectrum of phenotypes. They found pathogenic NIPBL mutations in 24 of them, whereas the remaining 33 cases did not bear any NIPBL mutation. Of these 33 individuals, there was only 1 instance of familial occurrence, with 2 male sibs, their mother, and a first cousin affected. Involvement of NIPBL was excluded in this family, but the affected individuals were found to carry a 3-bp deletion in the SMC1A gene (300040.0001). In addition, a sporadic case was found to have a de novo missense mutation in the SMC1A gene (300040.0002). Among 30 unrelated patients with CDLS, Pie et al. (2010) found that 11 (37%) patients had mutations in the NIPBL gene (608667), consistent with CDLS1 (122470), and 3 (10%) had mutations in the SMC1A gene, with an overall molecular diagnostic yield of 47%. None of the patients had mutations in the SMC3 gene. Most of the patients were of Spanish origin. Although those with NIPBL mutations had a more severe phenotype than those with SMC1A mutations, the incidence of palate defects was higher in those with SMC1A mutations. INHERITANCE \- X-linked dominant GROWTH Other \- Pre- and postnatal growth retardation HEAD & NECK Head \- Microcephaly \- Brachycephaly \- Bitemporal narrowing \- Micrognathia Face \- Long, smooth philtrum Eyes \- Arched eyebrows \- Synophrys \- Thick eyebrows \- Long eyelashes \- Ptosis \- Downslanting palpebral fissures Nose \- High nasal bridge \- Anteverted nares Mouth \- Thin upper lip \- Downturned corners of the mouth \- High-arched palate Neck \- Short neck CARDIOVASCULAR Heart \- Hypertrophic cardiomyopathy (1 patient) ABDOMEN Gastrointestinal \- Gastroesophageal reflux SKELETAL Limbs \- Limited elbow movement Hands \- Small hands \- Brachydactyly \- Clinodactyly \- Proximally placed thumbs Feet \- Small feet SKIN, NAILS, & HAIR Skin \- Cutis marmorata Hair \- Low anterior hairline \- Hirsutism NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Cognitive impairment \- Poor speech \- Seizures (in some patients) \- Enlarged ventricles MISCELLANEOUS \- Female mutation carriers are less severely affected than male mutation carriers MOLECULAR BASIS \- Caused by mutation in the structural maintenance of chromosomes 1A gene (SMC1A, 300040.0001 ) ▲ 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	CORNELIA DE LANGE SYNDROME 2	c0270972	25,077	omim	https://www.omim.org/entry/300590	2019-09-22T16:20:01	{"doid": ["0080506"], "mesh": ["D003635"], "omim": ["300590"], "orphanet": ["199"], "synonyms": ["Alternative titles", "CORNELIA DE LANGE SYNDROME, X-LINKED", "CDLS, X-LINKED"], "genereviews": ["NBK1104"]}
## Description Myopia, or nearsightedness, is a refractive error of the eye. Light rays from a distant object are focused in front of the retina and those from a near object are focused in the retina; therefore distant objects are blurry and near objects are clear (summary by Kaiser et al., 2004). For a discussion of genetic heterogeneity of susceptibility to myopia, see 160700. Mapping Hammond et al. (2004) undertook a classic twin study of 506 twin pairs, 280 dizygotic (DZ) and 226 monozygotic (MZ), to establish the heritability of refractive error as determined by mean spherical equivalent (SE). The mean SE for the 506 twin pairs was +0.39 diopters (D), with a range of -12.12 D to +7.25 D. Only 4 MZ and 3 DZ twin pairs were well within the high myopia range (more than -6.00 D). The heritability of refractive error was inferred to be 0.89. To ascertain potential susceptibility loci for myopia, Hammond et al. (2004) performed a genomewide linkage scan for the continuous trait using 221 of the DZ twin pairs. Maximum evidence for linkage was observed at chromosome 11p13 (MYP7; 609256), with a lod score of 6.1. Other linkage peaks were observed at chromosomes 3q26 (MYP8; 609257), 4q12 (MYP9; 609258), and 8p23 (MYP10), with lod scores of 3.7, 3.3, and 4.1, respectively. INHERITANCE \- Multifactorial HEAD & NECK Eyes \- Myopia, low to moderate (-12.12 D to +7.25 D) ▲ 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	MYOPIA 10	c1836503	25,078	omim	https://www.omim.org/entry/609259	2019-09-22T16:06:32	{"mesh": ["C563758"], "omim": ["609259"]}
A number sign (#) is used with this entry because progressive myoclonic epilepsy-4 (EPM4), also known as action myoclonus-renal failure syndrome (AMRF), is caused by homozygous or compound heterozygous mutations in the SCARB2 gene (602257) on chromosome 4q21. Description The action myoclonus-renal failure syndrome is an autosomal recessive progressive myoclonic epilepsy associated with renal failure. Cognitive function is preserved (Badhwar et al., 2004). Some patients do not develop renal failure (Dibbens et al., 2009). For a discussion of genetic heterogeneity of progressive myoclonic epilepsy, see EPM1A (254800). Clinical Features Andermann et al. (1981) observed 3 patients in 4 French Canadian sibships who developed tremor of the fingers and hands and proteinuria at 17 to 18 years of age. Severe progressive action myoclonus, dysarthria, ataxia, infrequent generalized seizures, and renal failure requiring dialysis and/or renal transplantation ensued between 19 and 23 years of age. Despite severe neurologic disability due mainly to action myoclonus, intelligence remained normal in patients who had survived as long as 14 years after renal transplantation. Nephrosialidosis, another disorder with combined neurologic and renal abnormalities, was excluded. Badhwar et al. (2004) reported 15 individuals with AMRF from 9 families originating from 5 different countries, including the U.S., Australia, Canada, Cuba, and Germany. Four of the patients had originally been reported by Andermann et al. (1981). Fine tremor of the fingers and hands was the first neurologic symptom with age at onset between 17 and 19 years. Involvement of the head, trunk, and sometimes the tongue occurred with progression of the disorder. Onset of action myoclonus occurred between 14 to 29 years and was the most debilitating feature of the disease. Asynchronous jerks were also present at rest. Many patients became bedridden or wheelchair-bound in the final stages. Convulsive seizures occurred in 73% of patients, with onset between 20 and 28 years. Other neurologic features included ataxia and dysarthria, and 8 patients had cerebellar atrophy on MRI. Proteinuria occurred in all cases between ages 9 to 30 years, and renal failure occurred in 12 of 15 patients within 8 years. Patients presented with neurologic symptoms (5), renal dysfunction (4), or both simultaneously (6). Nine patients died between ages 25 and 35 years, due to respiratory complications, renal failure, or complications of renal transplant. Badhwar et al. (2004) found that dialysis and renal transplantation were effective treatments for the renal failure but did not improve the neurologic condition. Autosomal recessive inheritance was observed. Vadlamudi et al. (2006) reported 2 unrelated patients with AMRF. The first patient, an Australian man of English descent, developed end-stage renal failure at age 20 years and was treated with dialysis. He also developed a mild, intermittent upper limb action tremor that was exacerbated by stress. At age 24, he had action tremor, myoclonus in the hands and legs, and reported occasional falls while playing sports. He had a renal transplant at age 24. In his late 20s, he developed problems with balance and writing, action myoclonus, postural tremor, gait ataxia, dysarthria, and seizures. The second patient was a Cypriot-born Australian woman born of first cousin parents. She developed focal segmental glomerulosclerosis at age 22 years and had a renal transplant at age 28. Neurologic symptoms began at age 25, with fine action tremor of the hands and deterioration in walking. She later developed worsening tremor, action myoclonus, gait ataxia, and dysarthria. Cognitive function was preserved in both patients. Vadlamudi et al. (2006) emphasized the difficulty in diagnosing this disorder in the early stages because tremor may be the only presenting feature. Balreira et al. (2008) reported 2 Portuguese sisters, born of consanguineous parents, with AMRF. The first sister presented at age 15 with myoclonic jerks of the upper arms. Symptoms progressed to involve the lower limbs, resulting in gait instability. Horizontal saccades and proteinuria developed at age 18. By age 20, she was totally dependent, unable to write, eat alone, or walk independently, and manifested dysarthria and dysphagia. She developed nephrotic syndrome with thrombocytopenia; renal biopsy showed tubular alterations with vacuolization in distal and collecting tubules and granular material in cortical tubules. There was also deposition of complement components. She died at age 23. A DNA sample from the first sister was not available for testing. The second sister had a similar phenotype with onset at age 17. Horizontal saccades developed at age 20, and by age 21 she presented nephrotic syndrome and was totally dependent 1 year later. At age 23, she had normocytic normochromic anemia and hypoalbuminemia but no thrombocytopenia. She died at age 26 years. Patient fibroblasts showed 10% residual beta-glucosidase (GBA; 606463) activity and an abnormal glycosylation pattern, consistent with depletion of post-Golgi forms of the enzyme. However, leukocytes showed normal GBA activity. ### Neuropathologic Findings Neuropathologic examination of 1 of the patients reported by Badhwar et al. (2004) showed extraneuronal accumulation of irregularly shaped, refractile, and autofluorescent pigmented granules in the cerebral cortex, the globus pallidus, and some areas of the cerebellar cortex. Renal pathology of several patients showed focal glomerulosclerosis, some with features of collapsing glomerulopathy. ### Clinical Variability Dibbens et al. (2009) identified 5 unrelated Italian patients with progressive myoclonic epilepsy due to SCARB2 mutations (see, e.g., 602257.0005-602257.0006) who did not develop renal failure. Age at onset ranged between 14 and 23 years, and the disorder was characterized by action myoclonus, tonic-clonic seizures, and later development of ataxia. Four patients died due to refractory seizures and immobility 10 to 15 years after onset, and none of 4 patients had developed renal failure. The fifth patient showed mild proteinuria at age 32 years, 5.5 years after onset. These 5 patients were ascertained from a larger group of 41 patients with progressive myoclonic epilepsy without dementia who were negative for mutations in the CSTB gene (601145), which is responsible for progressive myoclonic epilepsy-1 (EPM1; 254800). The findings of Dibbens et al. (2009) expanded the phenotype associated with SCARB2 mutations to include patients without renal involvement. Dibbens et al. (2011) provided follow-up of a patient with progressive myoclonic epilepsy without renal failure originally reported by Costello et al. (2009). He had onset of myoclonic epilepsy at age 16 years and became severely disabled, requiring a wheelchair by age 20. At age 27, he had intractable myoclonus, dysarthria, and dysphagia, but cognition remained intact and there was no evidence of renal failure. Electrophysiologic studies indicated a demyelinating peripheral neuropathy, with reduced sensory and motor action potentials and mildly decreased nerve conduction velocities. Dibbens et al. (2011) identified compound heterozygosity for 2 mutations in the SCARB2 gene (602257.0003 and 602257.0007). The findings reemphasized that SCARB2 mutations can cause EPM without renal failure. Inheritance Andermann et al. (1981) described AMRF in French Canadian sibships. One family had 2 affected sibs, and another was consanguineous. All patients were from the same ethnic group and geographic area, and family names were shared by the ancestors of all cases, consistent with autosomal recessive inheritance of the disorder. Mapping Studying only 3 unrelated affected individuals with ARMF and their relatives, Berkovic et al. (2008) used homozygosity mapping with single-nucleotide polymorphism (SNP) chips to localize the disorder to chromosome 4q13-q21. Molecular Genetics Using microarray expression analysis, Berkovic et al. (2008) identified the SCARB2 gene (602257) as a likely site of mutations causing AMRF within the critical region. Mutations in SCARB2 were found in all 3 families used for mapping and subsequently confirmed in 2 other unrelated AMRF families. The mutations were associated with lack of SCARB2 protein (see 602257.0001-602257.0003). In a Portuguese girl with progressive myoclonic epilepsy and nephrotic syndrome, Balreira et al. (2008) identified a homozygous mutation in the SCARB2 gene (W178X; 602257.0004). A DNA sample from her affected sister was not available for testing. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Horizontal saccades ABDOMEN Gastrointestinal \- Dysphagia GENITOURINARY Kidneys \- Renal failure \- Nephrotic syndrome \- Proteinuria \- Focal segmental glomerulosclerosis \- Collapsing glomerulopathy \- Vacuolization in distal and collecting tubules \- Granular material in cortical tubules \- Complement component deposition NEUROLOGIC Central Nervous System \- Action tremor \- Intention tremor \- Postural tremor \- Dysarthria \- Action myoclonus \- Resting myoclonus \- Gait ataxia \- Seizures, generalized \- No cognitive decline \- Extraneuronal accumulation of autofluorescent pigmented material in various brain regions \- Cerebellar atrophy HEMATOLOGY \- Thrombocytopenia (reported in 1 patient) LABORATORY ABNORMALITIES \- Proteinuria MISCELLANEOUS \- Onset in teens to 20's \- Rapidly progressive disorder \- Patients may present with either renal or neurologic symptoms \- Patients may become totally dependent for all activities of daily living \- Death occurs 10 to 20 years after onset \- Some patients do not develop renal failure MOLECULAR BASIS \- Caused by mutation in the scavenger receptor class B, member 2 gene (SCARB2, 602257.0001 ) ▲ 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	EPILEPSY, PROGRESSIVE MYOCLONIC, 4, WITH OR WITHOUT RENAL FAILURE	c0751779	25,079	omim	https://www.omim.org/entry/254900	2019-09-22T16:24:39	{"doid": ["891"], "mesh": ["D020191"], "omim": ["254900"], "orphanet": ["163696"], "synonyms": ["Alternative titles", "ACTION MYOCLONUS-RENAL FAILURE SYNDROME", "MYOCLONUS-NEPHROPATHY SYNDROME"], "genereviews": ["NBK333437"]}
In 5 sibships and 3 generations of a family originating from Upington district of the Cape Province, South Africa, Schweitzer et al. (1971) described a new 'dyschondroplasia' in which father-son transmission was noted. The features were Perthes-like hip changes, enchondromata and ecchondromata. Some similarities to Ollier disease and Maffucci disease were noted. The latter two conditions are, however, not mendelian. INHERITANCE \- Autosomal dominant SKELETAL \- Enchondromata (cartilaginous tumor growing from interior of bone) \- Ecchondromata (cartilaginous tumor projecting under periosteum) \- Arthralgias (hips, knees) Pelvis \- Premature closure of the capital femoral epiphyses \- Widened femoral necks \- Flattened femoral heads MISCELLANEOUS \- Onset at age 5 years \- Majority of cases have bilateral involvement ▲ 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	UPINGTON DISEASE	c1860596	25,080	omim	https://www.omim.org/entry/191520	2019-09-22T16:32:11	{"mesh": ["C536472"], "omim": ["191520"], "orphanet": ["3408"], "synonyms": ["Alternative titles", "PERTHES-LIKE HIP DISEASE, ENCHONDROMATA, AND ECCHONDROMATA"]}
A number sign (#) is used with this entry because Charcot-Marie-Tooth disease type 1F is caused by mutation in the NEFL gene (162280). For a phenotypic description and discussion of genetic heterogeneity of CMT type 1, see CMT1B (118200). Clinical Features Jordanova et al. (2003) reported 3 families with a form of autosomal dominant CMT1. Disease onset was in infancy or childhood (range 1 to 13 years), with distal limb muscle weakness and atrophy, worse in the lower limbs, distal sensory loss, diminished reflexes, pes cavus, and reduced motor nerve conduction velocity (NCV). Three sporadic patients with similar features were also described. Nerve biopsy of 1 of the sporadic patients showed loss of myelinated fibers, onion bulb formation, irregular myelin foldings, and clusters of axonal regeneration. Jordanova et al. (2003) noted that some of the patients were diagnosed with Dejerine-Sottas syndrome (DSS; 145900) because of early onset and increased severity. Abe et al. (2009) reported 5 unrelated Japanese patients with autosomal dominant demyelinating CMT caused by heterozygous mutations in the NEFL gene. Four had onset before age 2 years, and 1 had onset before age 10 years. Initial symptoms included delayed walking or gait disturbance. Other features included upper and lower muscle weakness and atrophy, distal sensory loss, and hypo- or areflexia. Nerve conduction velocities were severely decreased. Four patients had hearing disturbances, 1 had mental retardation, and 1 had pyramidal signs and cerebellar atrophy. Abe et al. (2009) also reported a patient with demyelinating CMT caused by a homozygous truncating mutation (162280.0007) in the NEFL gene. This patient was born of consanguineous parents and had onset before age 10 years. He had a similarly affected brother, but neither parent was affected. Abe et al. (2009) postulated that the nonsense mutation would result in loss of function, in contrast to missense mutations which result in toxic gain of function, and concluded that homozygous nonsense mutations in the NEFL gene cause a recessive disorder. Yum et al. (2009) reported a consanguineous Palestinian family in which 4 sibs had a severe, progressive peripheral neuropathy beginning in early childhood. All had hypotonia in infancy and early childhood, mildly delayed motor development, pes cavus, and slowly progressive atrophy and weakness in the distal muscles of the legs and arms. All also had moderate distal sensory impairment. Visual evoked responses were prolonged in 3 of 4 children, suggesting the involvement of central nervous system axons. Sural nerve biopsy of 1 patient showed lack of immunostaining for NEFL, decreased numbers of myelinated axons, and some regenerating axons. Intermediate filaments were not present in remaining myelinated axons. Although Yum et al. (2009) referred to this phenotype as an 'axonal' neuropathy, the median nerve conduction velocities in all affected patients ranged from 14 to 25 m/s, which is more consistent with a 'demyelinating' neuropathy, as in CMT1F. Molecular Genetics In 3 families and 3 sporadic patients with CMT1, Jordanova et al. (2003) identified mutations in the NEFL gene (see, e.g., 162280.0003 and 162280.0004). In 4 Palestinian sibs with severe early-onset neuropathy and decreased NCV, Yum et al. (2009) identified a homozygous mutation in the (E210X; 162280.0008) in the NEFL gene. The unaffected consanguineous parents were heterozygous for the mutation. In vitro functional expression studies showed that mutant NEFL did not accumulate properly, suggesting an inability to form filaments or enhanced degradation, consistent with a loss of function. Nomenclature In keeping with the most common designations used in the medical community, 'CMT1' referring to autosomal dominant demyelinating CMT and 'CMT2' referring to axonal CMT, we have chosen to designate this form of autosomal dominant demyelinating CMT caused by mutation in the NEFL gene as 'CMT1F.' INHERITANCE \- Autosomal dominant \- Autosomal recessive SKELETAL Feet \- Pes cavus NEUROLOGIC Peripheral Nervous System \- Delayed motor development \- Distal limb muscle weakness due to peripheral neuropathy \- Distal limb muscle atrophy due to peripheral neuropathy \- Distal sensory impairment \- Hyporeflexia \- Areflexia \- Decreased motor nerve conduction velocity (NCV) (less than 38 m/s) \- Segmental demyelination/remyelination on nerve biopsy \- 'Onion bulb' formation on nerve biopsy \- Loss of myelinated fibers \- Irregular myelin foldings \- Clusters of axonal regeneration MISCELLANEOUS \- Onset in infancy or childhood (range 1 to 13 years) \- Usually begins in feet and legs (peroneal distribution) \- Upper limb involvement usually occurs later \- Variable severity \- Autosomal recessive inheritance has been described in 2 families \- Genetic heterogeneity (see CMT1B 118200 ) MOLECULAR BASIS \- Caused by mutation in the neurofilament light chain gene (NEFL, 162280.0003 ) ▲ 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	CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 1F	c1843164	25,081	omim	https://www.omim.org/entry/607734	2019-09-22T16:08:50	{"doid": ["0110149"], "mesh": ["C537987"], "omim": ["607734"], "orphanet": ["101085", "228374"], "synonyms": ["Alternative titles", "CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 1F"]}
A rare pituitary disease characterized by hemorrhagic or non-hemorrhagic necrosis of the pituitary gland. Clinical manifestations typically comprise sudden and severe headache (often with nausea and vomiting), visual disturbances (visual-field defects, loss of visual acuity), oculomotor palsies, and variable degrees of altered consciousness, ranging from lethargy to coma. Acute endocrine dysfunction may also be present, most commonly corticotropic deficiency with severe hypotension and hyponatremia as well as secondary adrenal failure, but also thyrotropic and gonadotropic 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	Pituitary apoplexy	c0032001	25,082	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=95613	2021-01-23T17:07:36	{"mesh": ["D010899"], "umls": ["C0032001"], "icd-10": ["E23.6"], "synonyms": ["Pituitary tumor apoplexy"]}
Most common form of cutaneous T-cell lymphoma Mycosis fungoides Skin lesions on the knee of a 52-year-old male patient with Mycosis fungoides SpecialtyOncology Mycosis fungoides, also known as Alibert-Bazin syndrome or granuloma fungoides,[1] is the most common form of cutaneous T-cell lymphoma. It generally affects the skin, but may progress internally over time. Symptoms include rash, tumors, skin lesions, and itchy skin. While the cause remains unclear, most cases are not hereditary. Most cases are in people over 20 years of age, and it is more common in men than women. Treatment options include sunlight exposure, ultraviolet light, topical corticosteroids, chemotherapy, and radiotherapy. ## Contents * 1 Signs and symptoms * 2 Cause * 3 Diagnosis * 3.1 Staging * 3.2 Prognosis * 4 Treatment * 5 Epidemiology * 6 History * 7 Notable cases * 8 See also * 9 References * 10 Further reading * 11 External links ## Signs and symptoms[edit] Plaque of mycosis fungoides Plaque of mycosis fungoides on foot treated with imiquimod at Penn Medicine in Philadelphia, and then radiation at Lehigh Valley Hospital. The symptoms of mycosis fungoides are categorized into three clinical stages: the patch stage, the plaque stage, and the tumour stage.[2] The patch stage is defined by flat, reddish patches of varying sizes that may have a wrinkled appearance. They can also look yellowish in people with darker skin.[2] The plaque stage follows the patch stage of mycosis fungoides.[3] It is characterized by the presence of raised lesions that appear reddish-brown; in darker skin tones, plaques may have a greyish or silver appearance.[4] Both patch and plaque stages are considered early-stage mycosis fungoides.[3] The tumour stage typically shows large irregular lumps. Tumours can develop form plaques or normal skin in any region of the body, including the face and head regions.[5] Itching (pruritus) is common, perhaps in 20 percent of patients, but is not universal. The symptoms displayed are progressive, with early stages consisting of lesions presented as scaly patches. Lesions often initially develop on the trunk of the body in places that are rarely exposed to the sun, such as the buttocks.[2] The advanced stage of mycosis fungoides is characterized by generalized erythroderma (red rash covering most of the body) with severe pruritus (itching) and scaling.[4] The key difference between Sézary syndrome and the other stages of mycosis fungoides is the large number of cancer cells found in the blood (leukemic disease).[6] When mycosis fungoides develops to meet the criteria for Sézary syndrome, it is referred to as leukemic mycosis fungoides, Sézary syndrome preceded by mycosis fungoides, or secondary mycosis fungoides.[6] ## Cause[edit] The cause of mycosis fungoides is still unknown. However, there are a few current hypothesized causes of the disease. One of these hypotheses is that mycosis fungoides is caused by genetic and cellular signalling abnormalities. Examples of these abnormalities include clonal abnormalities and altered expression of adhesion molecules and/or cytokins.[7] Additionally, the disease is an unusual expression of CD4 T cells, a part of the immune system. These T cells are skin-associated, meaning they are biochemically and biologically most related to the skin, in a dynamic manner. Mycosis fungoides is the most common type of cutaneous T-cell lymphoma (CTCL), but there are many other types of CTCL that have nothing to do with mycosis fungoides and these disorders are treated differently.[medical citation needed] ## Diagnosis[edit] This section 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 section's tone or style may not reflect the encyclopedic tone used on Wikipedia. The reason given is: Appears to give medical advice, using terms like 'advisable' and 'recommended.' See Wikipedia's guide to writing better articles for suggestions. (August 2017) (Learn how and when to remove this template message) This section needs more medical references for verification or relies too heavily on primary sources, specifically: Information on peripheral smear cites a test-prep book. Please review the contents of the section and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed. Find sources: "Mycosis fungoides" – news · newspapers · books · scholar · JSTOR (August 2017) (Learn how and when to remove this template message) Diagnosis is sometimes difficult because the early phases of the disease often resemble inflammatory dermatoses (such as eczema, psoriasis, lichenoid dermatoses including lichen planus, vitiligo, and chronic cutaneous lupus erythematosus), as well as other cutaneous lymphomas.[8] Several biopsies are recommended, to be more certain of the diagnosis. The criteria for the disease are established on the skin biopsy:[9] * the superficial papillary dermis is infiltrated by a bandlike lymphocyte infiltrate * epidermotropism * presence of atypical T-cells with cerebriform nuclei in the dermal and epidermal infiltrates. Histopathology of Pautrier microabscesses in cutaneous T cell lymphoma. Pautrier's microabcesses are aggregates of four or more atypical lymphocytes arranged in the epidermis.[10] Pautrier microabcesses are characteristic of mycosis fungoides but are generally absent. To stage the disease, various tests may be ordered, to assess nodes, blood and internal organs, but most patients present with disease apparently confined to the skin, as patches (flat spots) and plaques (slightly raised or 'wrinkled' spots). Peripheral smear will often show buttock cells.[11] ### Staging[edit] Traditionally, mycosis fungoides has been divided into three stages: premycotic, mycotic and tumorous. The premycotic stage clinically presents as an erythematous (red), itchy, scaly lesion. Microscopic appearance is non-diagnostic and represented by chronic nonspecific dermatosis associated with psoriasiform changes in epidermis.[medical citation needed] In the mycotic stage, infiltrative plaques appear and biopsy shows a polymorphous inflammatory infiltrate in the dermis that contains small numbers of frankly atypical lymphoid cells. These cells may line up individually along the epidermal basal layer. The latter finding if unaccompanied by spongiosis is highly suggestive of mycosis fungoides. In the tumorous stage a dense infiltrate of medium-sized lymphocytes with cerebriform nuclei expands the dermis. Accurate staging of Mycosis Fungoides is essential to determine appropriate treatment and prognosis.[12] Staging is based on the tumor, node, metastasis, blood (TNMB) classification proposed by the Mycosis Fungoides Cooperative Group and revised by the International Society for Cutaneous Lymphomas/European Organization of Research and Treatment of Cancer.[12] This staging system examines the extent of skin involvement (T), presence of lymph node (N), visceral disease (M), and presence of Sezary cells in the peripheral blood (B).[12] Most patients with Mycosis Fungoides have early-stage disease (Stage IA-IIA) at the time of their initial diagnosis.[12] These patients with early stage disease that is primarily confined to the skin have a favorable prognosis.[12] Patients with advanced stage (Stage IIB-IVB) are often refractory to treatment and have an unfavorable prognosis.[12] Treatment of patients with advanced stage disease is designed to reduce tumor burden, delay disease progression, and preserve quality of life.[12] ### Prognosis[edit] A 1999 US-based study of patient records observed a 5-year relative survival rate of 77%, and a 10-year relative survival rate of 69%. After 11 years, the observed relative survival rate remained around 66%. Poorer survival is correlated with advanced age and black race. Superior survival was observed for married women compared with other gender and marital-status groups.[13] ## Treatment[edit] Mycosis fungoides can be treated in a variety of ways.[14] Common treatments include simple sunlight, ultraviolet light (mainly NB-UVB 312 nm), topical steroids, topical and systemic chemotherapies, local superficial radiotherapy, the histone deacetylase inhibitor vorinostat, total skin electron radiation, photopheresis and systemic therapies (e.g. interferons, retinoids, rexinoids) or biological therapies.[14] Treatments are often used in combination.[15] There is limited evidence for the efficacy of topical and systemic therapies for mycosis fungoides.[15] Due to the possible adverse effects of these treatments in early disease it is recommended to begin therapy with topical and skin-directed treatments before progressing to more systemic therapies.[15] Larger and more extensive research is needed to identify effective treatment strategies for this disease.[15] In 2010, the U.S. Food and Drug Administration granted orphan drug designation for naloxone lotion, a topical opioid receptor competitive antagonist used as a treatment for pruritus in cutaneous T-cell lymphoma.[16][17] The US FDA approved the drug mogamulizumab (trade name Poteligeo) in August 2018 for treatment of relapsed or refractory mycosis fungoides and Sézary disease.[18] ## Epidemiology[edit] It is rare for the disease to appear before age 20, and it appears to be noticeably more common in males than females, especially over the age of 50, where the incidence of the disease (the risk per person in the population) does increase. The average age of onset is between 45 and 55 years of age for patients with patch and plaque disease only, but is over 60 for patients who present with tumours, erythroderma (red skin) or a leukemic form (the Sézary syndrome). The incidence of mycosis fungoides was seen to be increasing till the year 2000 in the United States,[19] thought to be due to improvements in diagnostics. However, the reported incidence of the disease has since then remained constant,[20] suggesting another unknown reason for the jump seen before 2000. ## History[edit] Mycosis fungoides was first described in 1806 by French dermatologist Jean-Louis-Marc Alibert.[21][22] The name mycosis fungoides is very misleading—it loosely means "mushroom-like fungal disease". The disease, however, is not a fungal infection but rather a type of non-Hodgkin's lymphoma. It was so named because Alibert described the skin tumors of a severe case as having a mushroom-like appearance.[23] ## Notable cases[edit] In 1995 actor Mr. T was diagnosed with a cutaneous T-cell lymphoma, or mycosis fungoides.[24] Once in remission, he joked about the coincidence: "Can you imagine that? Cancer with my name on it — personalized cancer![25]" Popular British television actor Paul Eddington died of mycosis fungoides after living with the condition for four decades.[26] ## See also[edit] * Cutaneous T-cell lymphoma * Pagetoid reticulosis * Premycotic phase * Sézary's disease * Secondary cutaneous CD30+ large cell lymphoma * Angiocentric lymphoma * List of cutaneous conditions ## References[edit] 1. ^ synd/98 at Who Named It? 2. ^ a b c Harvey, Nathan T.; Spagnolo, Dominic V.; Wood, Benjamin A. (2015-12-01). "'Could it be mycosis fungoides?': an approach to diagnosing patch stage mycosis fungoides". Journal of Hematopathology. 8 (4): 209–223. doi:10.1007/s12308-015-0247-2. ISSN 1865-5785. 3. ^ a b Hristov, Alexandra C.; Tejasvi, Trilokraj; Wilcox, Ryan A. (September 2019). "Mycosis fungoides and Sézary syndrome: 2019 update on diagnosis, risk-stratification, and management". American Journal of Hematology. 94 (9): 1027–1041. doi:10.1002/ajh.25577. ISSN 1096-8652. PMID 31313347. 4. ^ a b Cerroni, Lorenzo (March 2018). "Mycosis fungoides-clinical and histopathologic features, differential diagnosis, and treatment". Seminars in Cutaneous Medicine and Surgery. 37 (1): 2–10. doi:10.12788/j.sder.2018.002. ISSN 1085-5629. PMID 29719014. 5. ^ Valipour, Arash; Jäger, Manuel; Wu, Peggy; Schmitt, Jochen; Bunch, Charles; Weberschock, Tobias (7 July 2020). "Interventions for mycosis fungoides". The Cochrane Database of Systematic Reviews. 7: CD008946. doi:10.1002/14651858.CD008946.pub3. ISSN 1469-493X. PMC 7389258. PMID 32632956. 6. ^ a b Larocca, Cecilia; Kupper, Thomas (February 2019). "Mycosis Fungoides and Sézary Syndrome: An Update". Hematology/Oncology Clinics of North America. 33 (1): 103–120. doi:10.1016/j.hoc.2018.09.001. ISSN 1558-1977. PMC 7147244. PMID 30497668. 7. ^ Khan Mohammad Beigi, Pooya. (2017). Clinician's Guide to Mycosis Fungoides. 10.1007/978-3-319-47907-1_9. 8. ^ Cerroni, L (March 2018). "Mycosis fungoides-clinical and histopathologic features, differential diagnosis, and treatment". Seminars in cutaneous medicine and surgery. 37 (1): 2–10. doi:10.12788/j.sder.2018.002. PMID 29719014. 9. ^ Canada, editors, John P. Greer, MD, Professor, Departments of Medicine and Pediatrics, Divisions of Hermatology/Oncology, Vanderbilt University Medical Center, Nashville, Tennessee; Daniel A. Arber, MD, Professor and Vice Chair, Department of Pathology, Stanford University, Director of Anatomic and Clinical Pathology Services, Stanford University Medical Center, Stanford, California; Bertil Glader, MD, Professor, Departments of Pediatrics and Pathology, Stanford University Medical Center, Stanford, California, Lucile Packard Children's Hospital, Palo Alto, California; Alan F. List, MD, Senior Member, Department of Malignant Hematology, President and CEO, Moffit Cancer Center, Tampa Florida; Robert T. Means Jr., MD, PhD, Professor of Internal Medicine, Executive Dean, University of Kentucky College of Medicine, Lexington, Kentucky; Frixos Paraskevas, MD, Professor of Internal Medicine and Immunology (Retired), University of Manitoba Medical School, Associate Member, Institute of Cell Biology-Cancer Care, Manitoba, Winnipeg, Manitoba, Canada; George M. Rodgers, MD, Professor of Medicine and Pathology, University of Utah School of Medicine, Health Sciences Center, Medical Director, Coagulation Laboratory, ARUB Laboratories, Salt Lake City, Utah; Editor Emeritus, John Foerster, MD, FRCPC, Professor and Physician Emertius, Winnipeg (2014). Wintrobe's clinical hematology (Thirteenth ed.). p. 1957. ISBN 978-1451172683.CS1 maint: extra text: authors list (link) 10. ^ al.], [edited by] Ronald Hoffman ... [et (2013). Hematology : basic principles and practice (6th ed.). Philadelphia, PA: Saunders/Elsevier. p. 1288. ISBN 978-1437729283.CS1 maint: extra text: authors list (link) 11. ^ O'Connell, Theodore X. (28 November 2013). USMLE Step 2 Secrets. Elsevier Health Sciences. p. 240. ISBN 9780323225021. 12. ^ a b c d e f g Jawed, Sarah I.; Myskowski, Patricia L.; Horwitz, Steven; Moskowitz, Alison; Querfeld, Christiane (February 2014). "Primary cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome)". Journal of the American Academy of Dermatology. 70 (2): 223.e1–223.e17. doi:10.1016/j.jaad.2013.08.033. 13. ^ Weinstock, Martin A.; Reynes, Josefina F. (1999). "The changing survival of patients with mycosis fungoides". Cancer. 85 (1): 208–212. doi:10.1002/(SICI)1097-0142(19990101)85:1<208::AID-CNCR28>3.0.CO;2-2. ISSN 0008-543X. 14. ^ a b Prince HM, Whittaker S, Hoppe RT (November 2009). "How I treat mycosis fungoides and Sézary syndrome". Blood. 114 (20): 4337–53. doi:10.1182/blood-2009-07-202895. PMID 19696197. 15. ^ a b c d Weberschock, Tobias; Strametz, Reinhard; Lorenz, Maria; Röllig, Christoph; Bunch, Charles; Bauer, Andrea; Schmitt, Jochen (2012-09-12). "Interventions for mycosis fungoides". The Cochrane Database of Systematic Reviews (9): CD008946. doi:10.1002/14651858.CD008946.pub2. ISSN 1469-493X. PMID 22972128. 16. ^ "Elorac, Inc. announces orphan drug designation for novel topical treatment for pruritus in cutaneous T-cell lymphoma (CTCL)". Archived from the original on 2010-12-30. Retrieved 2010-11-30. 17. ^ Wang H, Yosipovitch G (January 2010). "New insights into the pathophysiology and treatment of chronic itch in patients with end-stage renal disease, chronic liver disease, and lymphoma". International Journal of Dermatology. 49 (1): 1–11. doi:10.1111/j.1365-4632.2009.04249.x. PMC 2871329. PMID 20465602. 18. ^ "Press Announcements - FDA approves treatment for two rare types of non-Hodgkin lymphoma". 19. ^ Morales Suárez-Varela, M. M.; Llopis González, A.; Marquina Vila, A.; Bell, J. (2000). "Mycosis fungoides: review of epidemiological observations". Dermatology. 201 (1): 21–28. doi:10.1159/000018423. ISSN 1018-8665. PMID 10971054. S2CID 1544301. 20. ^ Korgavkar, Kaveri; Xiong, Michael; Weinstock, Martin (2013-11-01). "Changing incidence trends of cutaneous T-cell lymphoma". JAMA Dermatology. 149 (11): 1295–1299. doi:10.1001/jamadermatol.2013.5526. ISSN 2168-6084. PMID 24005876. 21. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 1867. ISBN 978-1-4160-2999-1. 22. ^ Alibert JLM (1806). Descriptions des maladies de la peau observées a l'Hôpital Saint-Louis, et exposition des meilleures méthodes suivies pour leur traitement (in French). Paris: Barrois l’ainé. p. 286. Archived from the original on 2012-12-12. 23. ^ Cerroni, 2007, p.13 24. ^ "Mr. T, T cell lymphoma survivor". 2013-05-30. 25. ^ "Mr. T - The Ultimate Tough Guy goes Head-to-Head with Cancer". copingmag.com. March 2000. Archived from the original on 2010-01-02. 26. ^ https://www.independent.co.uk/news/uk/actor-reveals-he-has-rare-skin-cancer-yes-minister-star-refuses-to-let-illness-remove-him-from-1419608.html ## Further reading[edit] * Knowles Daniel M (2000). Neoplastic Hematopathology. Lippincott Williams Wilkins. p. 1957. ISBN 978-0-683-30246-2. * Hwang ST, Janik JE, Jaffe ES, Wilson WH (March 2008). "Mycosis fungoides and Sézary syndrome". Lancet. 371 (9616): 945–57. doi:10.1016/S0140-6736(08)60420-1. PMID 18342689. S2CID 205950255. * Duvic M, Foss FM (December 2007). "Mycosis fungoides: pathophysiology and emerging therapies". Seminars in Oncology. 34 (6 Suppl 5): S21–8. doi:10.1053/j.seminoncol.2007.11.006. PMID 18086343. * Olsen E, Vonderheid E, Pimpinelli N, Willemze R, Kim Y, Knobler R, Zackheim H, Duvic M, Estrach T, Lamberg S, Wood G, Dummer R, Ranki A, Burg G, Heald P, Pittelkow M, Bernengo MG, Sterry W, Laroche L, Trautinger F, Whittaker S (September 2007). "Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC)". Blood. 110 (6): 1713–22. doi:10.1182/blood-2007-03-055749. PMID 17540844. ## External links[edit] Classification D * ICD-10: C84.0 * ICD-9-CM: 202.1 * ICD-O: M9700/3 * OMIM: 254400 * MeSH: D009182 * DiseasesDB: 8595 External resources * eMedicine: med/1541 * v * t * e Diseases of the skin and appendages by morphology Growths Epidermal * Wart * Callus * Seborrheic keratosis * Acrochordon * Molluscum contagiosum * Actinic keratosis * Squamous-cell carcinoma * Basal-cell carcinoma * Merkel-cell carcinoma * Nevus sebaceous * Trichoepithelioma Pigmented * Freckles * Lentigo * Melasma * Nevus * Melanoma Dermal and subcutaneous * Epidermal inclusion cyst * Hemangioma * Dermatofibroma (benign fibrous histiocytoma) * Keloid * Lipoma * Neurofibroma * Xanthoma * Kaposi's sarcoma * Infantile digital fibromatosis * Granular cell tumor * Leiomyoma * Lymphangioma circumscriptum * Myxoid cyst Rashes With epidermal involvement Eczematous * Contact dermatitis * Atopic dermatitis * Seborrheic dermatitis * Stasis dermatitis * Lichen simplex chronicus * Darier's disease * Glucagonoma syndrome * Langerhans cell histiocytosis * Lichen sclerosus * Pemphigus foliaceus * Wiskott–Aldrich syndrome * Zinc deficiency Scaling * Psoriasis * Tinea (Corporis * Cruris * Pedis * Manuum * Faciei) * Pityriasis rosea * Secondary syphilis * Mycosis fungoides * Systemic lupus erythematosus * Pityriasis rubra pilaris * Parapsoriasis * Ichthyosis Blistering * Herpes simplex * Herpes zoster * Varicella * Bullous impetigo * Acute contact dermatitis * Pemphigus vulgaris * Bullous pemphigoid * Dermatitis herpetiformis * Porphyria cutanea tarda * Epidermolysis bullosa simplex Papular * Scabies * Insect bite reactions * Lichen planus * Miliaria * Keratosis pilaris * Lichen spinulosus * Transient acantholytic dermatosis * Lichen nitidus * Pityriasis lichenoides et varioliformis acuta Pustular * Acne vulgaris * Acne rosacea * Folliculitis * Impetigo * Candidiasis * Gonococcemia * Dermatophyte * Coccidioidomycosis * Subcorneal pustular dermatosis Hypopigmented * Tinea versicolor * Vitiligo * Pityriasis alba * Postinflammatory hyperpigmentation * Tuberous sclerosis * Idiopathic guttate hypomelanosis * Leprosy * Hypopigmented mycosis fungoides Without epidermal involvement Red Blanchable Erythema Generalized * Drug eruptions * Viral exanthems * Toxic erythema * Systemic lupus erythematosus Localized * Cellulitis * Abscess * Boil * Erythema nodosum * Carcinoid syndrome * Fixed drug eruption Specialized * Urticaria * Erythema (Multiforme * Migrans * Gyratum repens * Annulare centrifugum * Ab igne) Nonblanchable Purpura Macular * Thrombocytopenic purpura * Actinic/solar purpura Papular * Disseminated intravascular coagulation * Vasculitis Indurated * Scleroderma/morphea * Granuloma annulare * Lichen sclerosis et atrophicus * Necrobiosis lipoidica Miscellaneous disorders Ulcers * Hair * Telogen effluvium * Androgenic alopecia * Alopecia areata * Systemic lupus erythematosus * Tinea capitis * Loose anagen syndrome * Lichen planopilaris * Folliculitis decalvans * Acne keloidalis nuchae Nail * Onychomycosis * Psoriasis * Paronychia * Ingrown nail Mucous membrane * Aphthous stomatitis * Oral candidiasis * Lichen planus * Leukoplakia * Pemphigus vulgaris * Mucous membrane pemphigoid * Cicatricial pemphigoid * Herpesvirus * Coxsackievirus * Syphilis * Systemic histoplasmosis * Squamous-cell carcinoma * v * t * e Leukaemias, lymphomas and related disease B cell (lymphoma, leukemia) (most CD19 * CD20) By development/ marker TdT+ * ALL (Precursor B acute lymphoblastic leukemia/lymphoma) CD5+ * naive B cell (CLL/SLL) * mantle zone (Mantle cell) CD22+ * Prolymphocytic * CD11c+ (Hairy cell leukemia) CD79a+ * germinal center/follicular B cell (Follicular * Burkitt's * GCB DLBCL * Primary cutaneous follicle center lymphoma) * marginal zone/marginal zone B-cell (Splenic marginal zone * MALT * Nodal marginal zone * Primary cutaneous marginal zone lymphoma) RS (CD15+, CD30+) * Classic Hodgkin lymphoma (Nodular sclerosis) * CD20+ (Nodular lymphocyte predominant Hodgkin lymphoma) PCDs/PP (CD38+/CD138+) * see immunoproliferative immunoglobulin disorders By infection * KSHV (Primary effusion) * EBV * Lymphomatoid granulomatosis * Post-transplant lymphoproliferative disorder * Classic Hodgkin lymphoma * Burkitt's lymphoma * HCV * Splenic marginal zone lymphoma * HIV (AIDS-related lymphoma) * Helicobacter pylori (MALT lymphoma) Cutaneous * Diffuse large B-cell lymphoma * Intravascular large B-cell lymphoma * Primary cutaneous marginal zone lymphoma * Primary cutaneous immunocytoma * Plasmacytoma * Plasmacytosis * Primary cutaneous follicle center lymphoma T/NK T cell (lymphoma, leukemia) (most CD3 * CD4 * CD8) By development/ marker * TdT+: ALL (Precursor T acute lymphoblastic leukemia/lymphoma) * prolymphocyte (Prolymphocytic) * CD30+ (Anaplastic large-cell lymphoma * Lymphomatoid papulosis type A) Cutaneous MF+variants * indolent: Mycosis fungoides * Pagetoid reticulosis * Granulomatous slack skin aggressive: Sézary disease * Adult T-cell leukemia/lymphoma Non-MF * CD30-: Non-mycosis fungoides CD30− cutaneous large T-cell lymphoma * Pleomorphic T-cell lymphoma * Lymphomatoid papulosis type B * CD30+: CD30+ cutaneous T-cell lymphoma * Secondary cutaneous CD30+ large-cell lymphoma * Lymphomatoid papulosis type A Other peripheral * Hepatosplenic * Angioimmunoblastic * Enteropathy-associated T-cell lymphoma * Peripheral T-cell lymphoma not otherwise specified (Lennert lymphoma) * Subcutaneous T-cell lymphoma By infection * HTLV-1 (Adult T-cell leukemia/lymphoma) NK cell/ (most CD56) * Aggressive NK-cell leukemia * Blastic NK cell lymphoma T or NK * EBV (Extranodal NK-T-cell lymphoma/Angiocentric lymphoma) * Large granular lymphocytic leukemia Lymphoid+ myeloid * Acute biphenotypic leukaemia Lymphocytosis * Lymphoproliferative disorders (X-linked lymphoproliferative disease * Autoimmune lymphoproliferative syndrome) * Leukemoid reaction * Diffuse infiltrative lymphocytosis syndrome Cutaneous lymphoid hyperplasia * Cutaneous lymphoid hyperplasia * with bandlike and perivascular patterns * with nodular pattern * Jessner lymphocytic infiltrate of the skin General * Hematological malignancy * leukemia * Lymphoproliferative disorders * Lymphoid leukemias [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Mycosis fungoides	c0026948	25,083	wikipedia	https://en.wikipedia.org/wiki/Mycosis_fungoides	2021-01-18T18:34:19	{"gard": ["3863"], "mesh": ["D009182"], "umls": ["C0026948"], "orphanet": ["2584"], "wikidata": ["Q1891209"]}
A rare, genetic congenital malformation syndrome characterized by digital anomalies (shortening of the 2nd and 5th middle phalanx of the hand, clinodactyly of the 5th finger, syndactyly of toes 2-3 and/or 4-5, thumb hypoplasia), microcephaly, facial dysmorphism (short palpebral fissures and micrognathia), gastrointestinal atresia (primarily esophageal and/or duodenal), and mild-to-moderate learning disability. ## Epidemiology The exact prevalence is unknown. Feingold syndrome type 1 (FS1) accounts for the vast majority of FS cases. An estimated 120 cases have been reported to date. ## Clinical description Characteristic clinical findings of FS1 are present at birth with digital anomalies being the most frequent and including: brachymesophalangy (most commonly affecting the 2nd and 5th fingers), thumb hypoplasia and toe syndactyly. Microcephaly and facial dysmorphism (short palpebral fissures, micrognathia) are also noted in most cases. The most serious manifestations that are noted in approximately half of cases are esophageal and duodenal (rarely jejunal or anal) atresia, with or without tracheo-esophageal fistula. The presence of a fistula can be indicated by signs such as coughing, gagging, vomiting, abdominal distension and, in some cases, respiratory distress. Gastrointestinal atresia must be treated immediately or it can be fatal. Mild learning deficits can become apparent in early childhood but severe intellectual disability is very rarely seen. ## Etiology FS1 is caused by a mutation or deletion in the proto-oncogene MYCN (2p24.3). It encodes a protein with a basic helix-loop-helix domain that is expressed at various stages of human embryonic development. ## Diagnostic methods Diagnosis is based on characteristic clinical features and imaging studies. Gastrointestinal atresia can be seen with pre-natal or post-natal ultrasound or by MRI. Molecular genetic testing can identify a MYCN mutation, confirming a diagnosis of FS1. ## Differential diagnosis Differential diagnosis of FS1 includes FS type 2 (FS2), VACTERL association, CHARGE syndrome, brachydactyly type A4 and Fanconi anemia. ## Antenatal diagnosis Prenatal testing is possible in FS1 families with a known MYCN mutation or deletion. ## Genetic counseling FS1 is inherited autosomal dominantly; however, most cases arise de novo. Genetic counseling is possible. ## Management and treatment xtensive medical examinations are needed to identify possible anomalies of the heart or kidneys. Management of FS1 (and FS2) typically centers on surgical correction of the specific congenital anomalies (certain types of cardiac malformations, and/or tracheo-esophageal fistula) in the immediate postnatal period, followed by long-term medical management of sequelae. Gastrointestinal atresia requires prompt treatment involving IV fluid administration and surgery. Optimal surgical treatment of infants with esophageal atresia and tracheoesophageal fistula remains controversial and gastroesophageal reflux (GER) is extremely frequent in patients treated for the two conditions. GER is refractory to medical treatment and often requires anti-reflux surgery. Renal and cardiac anomalies should receive the standard treatments and prophylactic antibiotics may be beneficial. Special education is recommended for children and adults with learning deficits. Hearing loss should equally be monitored by an audiologist. Cochlear implants are possible in certain cases. ## Prognosis Prognosis depends on congenital malformations (especially cardiac and renal anomalies) present. If optimal surgical correction is achievable, the prognosis can be relatively positive, though some patients will continue to be affected by their congenital malformations throughout life. * 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	Feingold syndrome type 1	c0796068	25,084	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=391641	2021-01-23T18:35:20	{"mesh": ["C537734"], "omim": ["164280"], "icd-10": ["Q87.8"], "synonyms": ["Brunner-Winter syndrome type 1", "Digital anomalies with short palpebral fissures and atresia of esophagus or duodenum type 1", "FGLDS1", "FS1", "MMT type 1", "MODED syndrome type 1", "Microcephaly-digital anomalies-normal intelligence syndrome type 1", "Microcephaly-intellectual disability-tracheoesophageal fistula syndrome type 1", "Microcephaly-oculo-digito-esophageal-duodenal syndrome syndrome type 1", "ODED syndrome type 1", "Oculo-digito-esophageal-duodenal syndrome type 1"]}
Orotic aciduria type I (OA1), also known as hereditary orotic aciduria, is a rare condition characterized by elevated levels of orotic acid in the urine. It typically becomes apparent in the first months of life with megaloblastic anemia, as well as delays in physical and intellectual development. OA1 is caused by changes (mutations) in the UMPS gene and inheritance is autosomal recessive. OA1 differs from other causes of orotic aciduria, which may include mitochondrial disorders, lysinuric protein intolerance, and liver disease. Treatment involves taking uridine; uridine triacetate was granted FDA approval for treating OA1 in 2015. Without treatment, children with OA1 may experience neutropenia, failure to thrive, developmental delay, and intellectual disability. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Orotic aciduria type 1	c0268130	25,085	gard	https://rarediseases.info.nih.gov/diseases/5429/orotic-aciduria-type-1	2021-01-18T17:58:33	{"mesh": ["C537136"], "omim": ["258900"], "umls": ["C0268130"], "orphanet": ["30"], "synonyms": ["Orotidylic pyrophosphorylase and orotidylic decarboxylase deficiency", "UMPS deficiency", "Uridine monophosphate synthase deficiency", "UMP synthtase deficiency", "Orotate phosphoribosyltransferase and omp decarboxylase deficiency", "UMPS", "Uridine monophosphate synthetase deficiency", "Hereditary orotic aciduria", "Orotic aciduria II (formerly)", "Oroticaciduria 1", "Hereditary orotic aciduria without megaloblastic anemia"]}
Choreoathetosis SpecialtyNeurology Choreoathetosis is the occurrence of involuntary movements in a combination of chorea (irregular migrating contractions) and athetosis (twisting and writhing). It is caused by many different diseases and agents. It is a symptom of several diseases, including Lesch–Nyhan syndrome, phenylketonuria, and Huntington disease and can be a feature of kernicterus (rapidly increasing unconjugated billirubin that cross the blood-brain-barrier in infants). Choreoathetosis is also a common presentation of dyskinesia as a side effect of levodopa-carbidopa in the treatment of Parkinson disease.[1] The use of crack cocaine can result in a condition of crack dancing described as choreathetoid.[2] ## See also[edit] * Ulegyria ## References[edit] 1. ^ "28". Basic and Clinical Pharmacology (Eleventh ed.). McGraw Hill Medical. July 2009. p. 473. ISBN 978-0-07-160405-5. 2. ^ Deik, A; Saunders-Pullman, R; Luciano, MS (September 2012). "Substance of abuse and movement disorders: complex interactions and comorbidities". Current Drug Abuse Reviews. 5 (3): 243–53. doi:10.2174/1874473711205030243. PMC 3966544. PMID 23030352. ## External links[edit] Classification D * ICD-10: G25.5 * ICD-9-CM: 333.5 * DiseasesDB: 16662 * v * t * e Diseases of the nervous system, primarily CNS Inflammation Brain * Encephalitis * Viral encephalitis * Herpesviral encephalitis * Limbic encephalitis * Encephalitis lethargica * Cavernous sinus thrombosis * Brain abscess * Amoebic Brain and spinal cord * Encephalomyelitis * Acute disseminated * Meningitis * Meningoencephalitis Brain/ encephalopathy Degenerative Extrapyramidal and movement disorders * Basal ganglia disease * Parkinsonism * PD * Postencephalitic * NMS * PKAN * Tauopathy * PSP * Striatonigral degeneration * Hemiballismus * HD * OA * Dyskinesia * Dystonia * Status dystonicus * Spasmodic torticollis * Meige's * Blepharospasm * Athetosis * Chorea * Choreoathetosis * Myoclonus * Myoclonic epilepsy * Akathisia * Tremor * Essential tremor * Intention tremor * Restless legs * Stiff-person Dementia * Tauopathy * Alzheimer's * Early-onset * Primary progressive aphasia * Frontotemporal dementia/Frontotemporal lobar degeneration * Pick's * Dementia with Lewy bodies * Posterior cortical atrophy * Vascular dementia Mitochondrial disease * Leigh syndrome Demyelinating * Autoimmune * Inflammatory * Multiple sclerosis * For more detailed coverage, see Template:Demyelinating diseases of CNS Episodic/ paroxysmal Seizures and epilepsy * Focal * Generalised * Status epilepticus * For more detailed coverage, see Template:Epilepsy Headache * Migraine * Cluster * Tension * For more detailed coverage, see Template:Headache Cerebrovascular * TIA * Stroke * For more detailed coverage, see Template:Cerebrovascular diseases Other * Sleep disorders * For more detailed coverage, see Template:Sleep CSF * Intracranial hypertension * Hydrocephalus * Normal pressure hydrocephalus * Choroid plexus papilloma * Idiopathic intracranial hypertension * Cerebral edema * Intracranial hypotension Other * Brain herniation * Reye syndrome * Hepatic encephalopathy * Toxic encephalopathy * Hashimoto's encephalopathy Both/either Degenerative SA * Friedreich's ataxia * Ataxia–telangiectasia MND * UMN only: * Primary lateral sclerosis * Pseudobulbar palsy * Hereditary spastic paraplegia * LMN only: * Distal hereditary motor neuronopathies * Spinal muscular atrophies * SMA * SMAX1 * SMAX2 * DSMA1 * Congenital DSMA * Spinal muscular atrophy with lower extremity predominance (SMALED) * SMALED1 * SMALED2A * SMALED2B * SMA-PCH * SMA-PME * Progressive muscular atrophy * Progressive bulbar palsy * Fazio–Londe * Infantile progressive bulbar palsy * both: * Amyotrophic lateral sclerosis This medical sign 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	Choreoathetosis	c0085583	25,086	wikipedia	https://en.wikipedia.org/wiki/Choreoathetosis	2021-01-18T18:37:29	{"icd-9": ["333.5"], "icd-10": ["G25.5"], "wikidata": ["Q3693493"]}
Juberg-Hayward syndrome is a polymalformative syndrome that associates multiple skeletal anomalies with microcephaly, facial dysmorphism, urogenital anomalies and intellectual deficit. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Juberg-Hayward syndrome	c0796099	25,087	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2319	2021-01-23T18:22:57	{"gard": ["3060"], "mesh": ["C537690"], "omim": ["216100"], "umls": ["C0796099"], "icd-10": ["Q87.0"], "synonyms": ["Cleft lip/palate-abnormal thumbs-microcephaly syndrome", "Orocraniodigital syndrome"]}
A rare bacterial infectious disease characterized by an affliction of the upper respiratory tract mediated by the toxin of Corynebacterium diphtheriae. Symptoms include formation of an inflammatory pseudomembrane, fever, sore throat, headaches, coughing, dysphagia, dyspnea, and prominently swollen cervical lymph nodes. The disease may lead to respiratory failure and severe toxin-mediated damage of internal organs, including the heart and kidneys. A cutaneous form of diphtheria is more common in tropical climates and usually follows an indolent course. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Diphtheria	c0012546	25,088	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1679	2021-01-23T18:31:24	{"gard": ["1875"], "mesh": ["D004165"], "umls": ["C0012546"], "icd-10": ["A36.0", "A36.1", "A36.2", "A36.3", "A36.8", "A36.9"]}
A number sign (#) is used with this entry because of evidence that autosomal dominant deafness-13 (DFNA13) is caused by heterozygous mutation in the COL11A2 gene (120290) on chromosome 6p21. Clinical Features Brown et al. (1997) described a family with autosomal dominant nonsyndromic postlingual hearing loss. Affected individuals experienced progressive hearing loss beginning in the second to fourth decades, eventually making use of amplification mandatory. The family was of northern European extraction living in Iowa. Mapping In a family with autosomal dominant nonsyndromic postlingual hearing loss, Brown et al. (1997) mapped the disorder to chromosome 6p in a 4-cM interval flanked by D6S1663 and D6S1691, with a maximum 2-point lod score of 6.4 at D6S299. In a comprehensive review of nonsyndromic hearing impairment, Van Camp et al. (1997) referred to a family with postlingual progressive hearing loss in which linkage studies mapped the locus to 6p21.3 (Brown et al., 1997). They designated the disorder DFNA13. Molecular Genetics In an American and a Dutch family with autosomal dominant nonsyndromic nonprogressive hearing loss affecting predominantly the middle frequencies, McGuirt et al. (1999) identified heterozygosity for 2 different missense mutations in the COL11A2 gene (120290.0005 and 120290.0006, respectively). INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Congenital non-progressive, non-syndromic sensorineural hearing loss (greater mid frequency than low- or high-frequency loss) MISCELLANEOUS \- Allelic disorder to Stickler syndrome 3 ( 184840 ) \- Allelic disorder to OSMED ( 215150 ) Allelic disorder to Weissenbacher-Zweymuller syndrome ( 277610 ) MOLECULAR BASIS \- Caused by mutation in the collagen XI, alpha-2 polypeptide gene (COL11A2, 120290.0005 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	DEAFNESS, AUTOSOMAL DOMINANT 13	c1866095	25,089	omim	https://www.omim.org/entry/601868	2019-09-22T16:14:11	{"doid": ["0110545"], "mesh": ["C566612"], "omim": ["601868"], "orphanet": ["90635"], "synonyms": ["Autosomal dominant isolated neurosensory deafness type DFNA", "Autosomal dominant isolated neurosensory hearing loss type DFNA", "Autosomal dominant isolated sensorineural deafness type DFNA", "Autosomal dominant isolated sensorineural hearing loss type DFNA", "Autosomal dominant non-syndromic neurosensory deafness type DFNA", "Autosomal dominant non-syndromic neurosensory hearing loss type DFNA", "Autosomal dominant non-syndromic sensorineural hearing loss type DFNA"], "genereviews": ["NBK1434"]}
A rare congenital tricuspid malformation characterized by narrowing of the tricuspid valve orifice due to congenital valve anomalies, such as incompletely developed leaflets, shortened and malformed chordae tendineae, small annulus, and/or abnormal number and size of papillary muscles, resulting in right ventricular inflow obstruction. Clinical presentation depends on the degree of stenosis, as well as the presence or absence of additional cardiac anomalies, and includes easy fatigability, swelling of the lower limbs, and hepatomegaly, among others. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Congenital tricuspid stenosis	c0265836	25,090	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=95459	2021-01-23T16:59:48	{"umls": ["C0265836"], "icd-10": ["Q22.4"]}
Type 1 lissencephaly due to doublecortin (DCX) gene mutations is a semi-dominant X-linked disease characterised by intellectual deficiency and seizures that are more severe in male patients. ## Epidemiology The prevalence is unknown. ## Clinical description Boys presenting with lissencephaly show an abnormally thick cortex with very few gyri (pachygyria) or even none (agyria). Clinical manifestations include swallowing and feeding difficulties, abnormal muscular tone, seizures and severe to profound psychomotor retardation. Female patients display a less severe malformation referred to as ''doublecortex'' or subcortical laminar heterotopia (SCLH) and present with clinical signs of variable severity ranging from mild epilepsy, beginning in childhood or adolescence with difficulties at school, to refractory epileptic seizures and severe intellectual deficiency. ## Etiology The condition is caused by doublecortin (DCX, located at Xq22.3-q23) gene mutations. These mutations lead to a specific defect of neuronal migration during embryogenesis, affecting all the neurons in males (lissencephaly) or only a population of neurons in heterozygous females, explaining why affected females display the less severe SCLH malformation. The DCX gene is linked to 50% of the cases of agyria, 33% of frontal pachygyria cases and 75% of SCLH cases. There is no correlation between the type of mutation and the severity of the disease. The group of type I lissencephalies includes Miller-Dieker syndrome and isolated lissencephalies linked to a deletion or point mutation in the LIS1 gene located on chromosome 17 (see these terms). In contrast to lissencephaly resulting from mutations in DCX, these types of lissencephaly are never familial. ## Diagnostic methods The diagnosis of subcortical laminar heterotopia and lissencephaly relies on magnetic resonance imaging (MRI). There seems to be a correlation between the degree of pachygyria of the cortex, widening of the ventricles, and thickness of laminar heterotopia on the one hand, and early onset of attacks and severity of intellectual deficiency on the other hand. ## Differential diagnosis SCLH should be distinguished from periventricular nodular heterotopia (see this term), which is also observed in girls, and is caused by a mutation in the filamin A gene, also located on the X chromosome. The clinical picture is milder with later onset and moderate epilepsy occurring in the young adult. ## Genetic counseling The molecular diagnosis of SCLH and lissencephaly is useful for genetic counselling and potential early antenal diagnosis of this very severe epileptogenic encephalopathy, before the stage when gyri normally appear (15 weeks of amenorrhea). If the mother carries the mutation, her risk of having a child with the mutation is 50%. Even when the mutation fails to be detected in the mother's blood, a risk nevertheless exists for future pregnancies, due to germinal mosaicism (5% to 10% of the cases). ## Management and treatment Antiepileptic medication generally succeeds in controlling epilepsy, although in some cases seizures do not completely resolve despite the use of several drugs. A gastric catheter or even a gastrotomy may be necessary to prevent complications linked to swallowing and feeding difficulties (malnutrition, regurgitation-induced pneumopathy). Orthopaedic problems (hip luxation, progressive scoliosis) can be prevented by posture correction and use of a surgical corset, which allow surgery to be delayed or avoided. ## Prognosis The prognosis depends on the degree of cerebral involvement. Lissencephaly is a severe disease, potentially associated with multiple impairments. The prognosis of SCLH is more variable, and depends on the severity of learning difficulties and epilepsy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Lissencephaly type 1 due to doublecortin gene mutation	c1848199	25,091	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2148	2021-01-23T17:36:58	{"mesh": ["D054221"], "omim": ["300067"], "umls": ["C1848199"], "icd-10": ["Q04.3"], "synonyms": ["X-linked lissencephaly type 1"]}
Lower limb malformation-hypospadias syndrome is a rare developmental defect during embryogenesis characterized by severe, uni- or bilateral lower limb malformations (incl. tibial hypoplasia, split and rocker bottom-shaped feet, and oligosyndactyly), normal upper limbs and hypospadias. Additional dysmorphic features (e.g. short neck and low-set, large ears), atrial septal defect, ureteropelvic junction stenosis and slight septation of the spleen, have also been reported. There have been no further descriptions in the literature since 1977. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Lower limb malformation-hypospadias syndrome	c2930962	25,092	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2487	2021-01-23T18:04:33	{"mesh": ["C535640"], "umls": ["C2930962"], "synonyms": ["Fried-Goldberg-Mundel syndrome"]}
Rare autoimmune disease Mixed autoimmune hemolytic anemia SpecialtyHematology Mixed autoimmune hemolytic anemia (MAIHA) is a type of autoimmune hemolytic anemia which combines the features of cold sensitive antibodyinduced diseases and warm autoimmune hemolytic anemia. The work-up for diagnosis is complex and the condition can be over-diagnosed.[1][2][better source needed] People diagnosed with warm autoimmune hemolytic anemia (WAIHA) caused by immunoglobulin G (IgG)[3] may also have a high number of immunoglobulin M (IgM) antibodies. These antibodies are active at room temperature, but are believed to be harmless since they are not the main antibodies responsible for WAIHA.[citation needed] However, studies revealed the existence of a few cases of WAIHA that may also carry cold agglutinin antibodies that are active at the environment where the temperatures is generally equal to or warmer than 30 °C (86 °F). Such coexistence suggests a diagnosis of the mixed (warm- and cold-antibody) autoimmune hemolytic anemia abbreviated as MAIHA.[4][better source needed] Mixed warm and cold AIHA runs a chronic course with severe intermittent exacerbations, such as serious anemia, and is treated by blood transfusion. Successful therapeutic options for the treatment of hemolysis associated with mixed AIHA are limited but increasing.[5][non-primary source needed][6][better source needed] In the past, there were two obvious sources of error regarding the diagnosis of AIHA. First, patients with w-AIHA can produce low-titer, low-thermal amplitude CA of no clinical significance. Second, up to 20% of patients with CAD have IgG on the RBC surface in addition to C3d.[7][1][6][non-primary source needed] ## See also[edit] * Thermal amplitude ## References[edit] 1. ^ a b Mayer, Beate; Yürek, Salih; Kiesewetter, Holger; Salama, Abdulgabar (2008). "Mixed-type autoimmune hemolytic anemia: differential diagnosis and a critical review of reported cases". Transfusion. Wiley. 48 (10): 2229–2234. doi:10.1111/j.1537-2995.2008.01805.x. ISSN 0041-1132. PMID 18564390. S2CID 46182439. 2. ^ Berentsen, Sigbjørn; Sundic, Tatjana (2015-01-29). "Red Blood Cell Destruction in Autoimmune Hemolytic Anemia: Role of Complement and Potential New Targets for Therapy". BioMed Research International. Hindawi Limited. 2015: 363278. doi:10.1155/2015/363278. ISSN 2314-6133. PMC 4326213. PMID 25705656. 3. ^ "Orphanet: Autoimmune hemolytic anemia, warm type". Orphanet. 2019-02-14. Retrieved 2019-02-15. 4. ^ Das, SudiptaSekhar; Chakrabarty, Ritam; Zaman, RU (2018). "Immunohematological and clinical characterizations of mixed autoimmune hemolytic anemia". Asian Journal of Transfusion Science. Medknow. 12 (2): 99–104. doi:10.4103/ajts.ajts_105_17. ISSN 0973-6247. PMC 6327768. PMID 30692792. 5. ^ Gupta, Shilpi; Szerszen, Anita; Nakhl, Fadi; Varma, Seema; Gottesman, Aaron; Forte, Frank; Dhar, Meekoo (2011-04-19). "Severe refractory autoimmune hemolytic anemia with both warm and cold autoantibodies that responded completely to a single cycle of rituximab: a case report". Journal of Medical Case Reports. Springer Nature. 5 (1): 156. doi:10.1186/1752-1947-5-156. ISSN 1752-1947. PMC 3096571. PMID 21504611. 6. ^ a b Berentsen, Sigbjørn; Sundic, Tatjana (2015-01-29). "Red Blood Cell Destruction in Autoimmune Hemolytic Anemia: Role of Complement and Potential New Targets for Therapy". BioMed Research International. Hindawi Limited. 2015. 363278-1–363278-11. doi:10.1155/2015/363278. ISSN 2314-6133. PMC 4326213. PMID 25705656. 7. ^ Berentsen, S; Ulvestad, E; Langholm, R; Beiske, K; Hjorth-Hansen, H; Ghanima, W; Sørbø, JH; Tjønnfjord, GE (2006). "Primary chronic cold agglutinin disease: a population based clinical study of 86 patients". Haematologica. 91 (4): 460–6. ISSN 0390-6078. PMID 16585012. * v * t * e Diseases of red blood cells ↑ Polycythemia * Polycythemia vera ↓ Anemia Nutritional * Micro-: Iron-deficiency anemia * Plummer–Vinson syndrome * Macro-: Megaloblastic anemia * Pernicious anemia Hemolytic (mostly normo-) Hereditary * enzymopathy: Glucose-6-phosphate dehydrogenase deficiency * glycolysis * pyruvate kinase deficiency * triosephosphate isomerase deficiency * hexokinase deficiency * hemoglobinopathy: Thalassemia * alpha * beta * delta * Sickle cell disease/trait * Hereditary persistence of fetal hemoglobin * membrane: Hereditary spherocytosis * Minkowski–Chauffard syndrome * Hereditary elliptocytosis * Southeast Asian ovalocytosis * Hereditary stomatocytosis Acquired AIHA * Warm antibody autoimmune hemolytic anemia * Cold agglutinin disease * Donath–Landsteiner hemolytic anemia * Paroxysmal cold hemoglobinuria * Mixed autoimmune hemolytic anemia * membrane * paroxysmal nocturnal hemoglobinuria * Microangiopathic hemolytic anemia * Thrombotic microangiopathy * Hemolytic–uremic syndrome * Drug-induced autoimmune * Drug-induced nonautoimmune * Hemolytic disease of the newborn Aplastic (mostly normo-) * Hereditary: Fanconi anemia * Diamond–Blackfan anemia * Acquired: Pure red cell aplasia * Sideroblastic anemia * Myelophthisic Blood tests * Mean corpuscular volume * normocytic * microcytic * macrocytic * Mean corpuscular hemoglobin concentration * normochromic * hypochromic Other * Methemoglobinemia * Sulfhemoglobinemia * Reticulocytopenia [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Mixed autoimmune hemolytic anemia	None	25,093	wikipedia	https://en.wikipedia.org/wiki/Mixed_autoimmune_hemolytic_anemia	2021-01-18T18:42:38	{"orphanet": ["90036"], "synonyms": ["Mixed AIHA"], "wikidata": ["Q55788708"]}
Silberberg and Silberberg (1967) defined the term 'hyperlexia' to describe children who read at levels beyond those expected for their mental age in the face of disordered oral communication. Turkeltaub et al. (2004) stated that there are 3 consistent features of hyperlexia: the presence of a developmental disorder of communication, most often an autistic spectrum disorder (209850); acquisition of reading skills prior to age 5 years without explicit instruction; and advanced word recognition ability relative to mental age, with reading comprehension on par with verbal ability. Among a group of 66 children with autism, Burd et al. (1985) identified 4 with hyperlexia. Burd and Kerbeshian (1988) described a brother and sister who began reading at about age 3 before receiving instruction and spent much time thereafter reading from encyclopedias, dictionaries, almanacs, and newspapers at ages 4 to 6. Both were thought to have 'pervasive developmental disorder,' which includes autism and Tourette syndrome (137580). Using functional MRI (fMRI) to study a 9-year-old boy with hyperlexia during covert reading, Turkeltaub et al. (2004) found greater activity in the left inferior frontal and posterior superior temporal cortical areas, and in the right inferior temporal cortical areas compared to controls. The authors suggested that precocious reading simultaneously draws on both left hemisphere phonologic and right hemisphere visual systems. The boy's reading comprehension ability fell in the average range, despite his advanced word decoding rate and accuracy and high IQ, further suggesting a diversion of attention resources from semantic aspects of reading to phonologic and visual aspects. Turkeltaub et al. (2004) noted that dyslexia (see 127700) had been associated with hypoactivation of the left superior temporal cortex. INHERITANCE \- Autosomal recessive \- Isolated cases \- Multifactorial NEUROLOGIC Behavioral Psychiatric Manifestations \- Developmental disorder of communication \- Autism ( 209850 ) \- Pervasive developmental disorder \- Precocious reading \- Reading at level beyond mental age \- Advanced word recognition \- Increased phonologic processing \- Reading comprehension on par with verbal abilities \- Functional MRI (fMRI) shows increased activity in the left inferior frontal cortex \- Increased activity in the left posterior superior temporal cortex \- Increased activity in the right inferior temporal cortex MISCELLANEOUS \- Onset before age 5 years in the absence of instruction ▲ 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	HYPERLEXIA	c1855928	25,094	omim	https://www.omim.org/entry/238350	2019-09-22T16:26:51	{"mesh": ["C565500"], "omim": ["238350"], "synonyms": ["Alternative titles", "COMPULSIVE READING", "PRECOCIOUS READING"]}
Familial isolated hypoparathyroidism (FIH) is a rare heterogeneous group of metabolic disorders characterized by abnormal calcium metabolism due to deficient secretion of parathormone (PTH), without other endocrine disorders or developmental defects. ## Clinical description It can occur at any age (from the newborn period to adulthood) but generally starts within the first decade of life. Diagnosis is made when hypocalcemia, hyperphosphoremia, and low or undetectable PTH levels are observed. The clinical signs are mainly those of hypocalcemia: myopathy, muscular weakness, cramps, tetany, lenticular cataracts, teeth anomalies and short stature. ## Etiology FIH may be due to an activating mutation of the calcium-sensing receptor (CASR) gene. This is the most common cause of genetic hypoparathyroidism and is transmitted as an autosomal dominant trait. It represents 42% of isolated hypoparathyroidism cases. Thirteen mutations have been described in familial or sporadic cases. In three families, mutations in the PTH gene have been identified. This type of FIH is transmitted as an autosomal recessive or dominant trait. One family has been reported with a mutation in the gene encoding the glial cells missing homolog b (GCMB) transcription factor. In this case, transmission is autosomal recessive. ## Genetic counseling Isolated hypoparathyroidism may be sporadic or familial, with autosomal dominant or recessive inheritance. ## Management and treatment Management consists of symptomatic treatment with supplementary calcium and vitamin D. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Familial isolated hypoparathyroidism	c1832648	25,095	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2238	2021-01-23T18:52:17	{"gard": ["2910"], "mesh": ["C537156"], "omim": ["146200", "307700", "601198", "615361"], "umls": ["C1832648"], "icd-10": ["E20.8"]}
Spondyloepiphyseal dysplasia (SED) Maroteaux type is a rare skeletal dysplasia that is characterized by short stature beginning in infancy, short, stubby hands and feet, and genu valgum (knock knees). In addition to these physical characteristics, individuals with SED Maroteaux type have some common radiographic findings, including platyspondyly (flattened vertebral bodies in the spine), abnormalities of the pelvis and severe brachydactyly (short fingers and toes). Intelligence is generally normal and there is no clouding of the cornea, which distinguishes SED Maroteaux type from other forms of spondyloepiphyseal dysplasia. SED Maroteaux type is caused by mutations in the TRPV4 gene and is inherited any an autosomal dominant fashion. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Spondyloepiphyseal dysplasia Maroteaux type	c3159322	25,096	gard	https://rarediseases.info.nih.gov/diseases/994/spondyloepiphyseal-dysplasia-maroteaux-type	2021-01-18T17:57:32	{"mesh": ["C563218"], "omim": ["184095"], "umls": ["C1300264"], "orphanet": ["263482"], "synonyms": ["Brachyolmia Maroteaux type", "Brachyolmia type 2", "SED, Maroteaux type", "Pseudo-Morquio syndrome type 2", "Spondyloepiphyseal dysplasia, Maroteaux type"]}
Vasculitic neuropathy SpecialtyNeurology Vasculitic neuropathy is a peripheral neuropathic disease.[1][2][3] In a vasculitic neuropathy there is damage to the vessels that supply blood to the nerves.[1][2][3] It can be as part of a systemic problem or can exist as a single-organ issue only affecting the peripheral nervous system (PNS).[1][2][3] It is diagnosed with the use of electrophysiological testing, blood tests, nerve biopsy and clinical examination. It is a serious medical condition that can cause prolonged morbidity and disability and generally requires treatment. Treatment depends on the type but it is mostly with corticosteroids or immunomodulating therapies. ## Contents * 1 Types * 1.1 Primary systemic vasculitic neuropathy * 1.2 Vasculitic neuropathy secondary to other disease * 1.3 Non-systemic vasculitic neuropathy * 1.3.1 'Classical' distal-predominant NSVN * 1.3.2 Warternberg migratory sensory neuropathy * 1.3.3 Postsurgical inflammatory neuropathy * 2 Diagnosis * 3 Treatments * 4 References ## Types[edit] There are three main categories of vasculitic neuropathies: primary, secondary and non-systemic.[2] ### Primary systemic vasculitic neuropathy[edit] Some patients with systemic vasculitis will have their multi-organ disease spread to the peripheral nervous system; this is primary vasculitic neuropathy. Some examples of systemic vasculitic disease are: IgA vasculitis, Hypocomplementemic urticarial vasculitis, polyarteritis nodosa (PAN) and anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides such as granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA) and microscopic polyangiitis (MPA).[1][3] ### Vasculitic neuropathy secondary to other disease[edit] Some patients with a non-vasculitic systemic disease or another illness such as infection or malignancy can subsequently develop vasculitic neuropathy as a direct consequence of the former illness; this is secondary vasculitic neuropathy. Some examples of such illness which can cause vasculitic neuropathy are: * Connective tissue diseases: rheumatoid arthritis, systemic lupus erythematosus, primary sjögren's, dermatomyositis. * Infectious diseases: hepatitis B, hepatitis C, human immunodeficiency virus (HIV), cytomegalovirus, lyme disease, human T-cell-lymphotrophic virus-I, parvovirus B19. * Malignancy. * Drugs. * Vaccinations. ### Non-systemic vasculitic neuropathy[edit] Non-systemic vasculitic neuropathy (NSVN) is a diagnosis of elimination. When no systemic illness can be found, yet evidence of a vasculitic neuropathy exists, a diagnosis of non-systemic vasculitic neuropathy is made. It is a single-organ problem. A nerve biopsy is required in order to make the diagnosis of non-systemic vaculitic neuropathy. There are distinct subtypes of NSVN with evolving cateregorisation in the literature. Currently accept subtypes are:[2][3] * 'Classical' distal-predominant NSVN * Wartenberg migratory sensory neuropathy * Post-surgical inflammatory neuropathy * Diabetic radiculoplexus neuropathy (lumbosacral, thoracic or cervical predominant) * Neuralgic amyotrophy * Non-systemic skin/nerve vasculitis (for example, cutaneous PAN) #### 'Classical' distal-predominant NSVN[edit] There is ongoing debate over this categorisation, particularly its overlap with the condition non-diabetic radiculoplexus neuropathy. As the name suggests it involves a clinical picture where the nerve damage is distally predominant as demonstrated in a nerve biopsy.[3] #### Warternberg migratory sensory neuropathy[edit] Warternberg migratory sensory neuropathy is typically a multi-focal neuropathy where there is pure sensory deficits. It is characterised by sudden-onset and chronicity as well as having a propensity for relapse. It generally resolves slowly with time.[3] #### Postsurgical inflammatory neuropathy[edit] Postsurgical inflammatory neuropathy is typically a multi-focal neuropathy which manifests thirty days after a surgical procedure. It mostly presents with motor and sensory symptoms. It is generally a self-limiting condition that has resolved with and without treatment.[3] ## Diagnosis[edit] Diagnosis of a vasculitic neuropathy depends on whether the patient first presents with multiple symptoms pointing at a systemic disorder or else primary neuropathic complaints. In the former case the patient is more likely to be assessed first by a rheumatologist and in the latter a neurologist or neurosurgeon. ## Treatments[edit] Treatment of vasculitic neuropathy depends on the type. ## References[edit] 1. ^ a b c d Graf, Jonathan; Imboden, John (January 2019). "Vasculitis and peripheral neuropathy:". Current Opinion in Rheumatology. 31 (1): 40–45. doi:10.1097/BOR.0000000000000559. ISSN 1040-8711. 2. ^ a b c d e Collins, Michael P.; Dyck, P. James B.; Hadden, Robert D.M. (October 2019). "Update on classification, epidemiology, clinical phenotype and imaging of the nonsystemic vasculitic neuropathies:". Current Opinion in Neurology. 32 (5): 684–695. doi:10.1097/WCO.0000000000000727. ISSN 1350-7540. 3. ^ a b c d e f g h Collins, Michael P.; Hadden, Robert D. (May 2017). "The nonsystemic vasculitic neuropathies". Nature Reviews Neurology. 13 (5): 302–316. doi:10.1038/nrneurol.2017.42. ISSN 1759-4758. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Vasculitic neuropathy	c1960443	25,097	wikipedia	https://en.wikipedia.org/wiki/Vasculitic_neuropathy	2021-01-18T19:04:13	{"umls": ["C1960443"], "wikidata": ["Q85812811"]}
Abortion in Slovenia was legalized in its current form (in Slovenia and the other former Yugoslav republics) on October 7, 1977.[1][2] Abortion is available on-demand for women whose pregnancies have not exceeded the tenth week. Minors require parental consent before undergoing an abortion unless the minor is already emancipated and earning her own living.[1] After Slovenia earned its independence from Yugoslavia, an amendment was made to the abortion law in 1992 allowing doctors to exempt themselves from performing abortions if they disagree with the practice for religious reasons.[1] In 2009, 18% of pregnancies in Slovenia ended in abortion, down from a peak of 41.6% in 1982.[3] As of 2009[update], the abortion rate was 11.5 abortions per 1000 women aged 15–44 years.[4] Mifepristone (medical abortion) was registered in 2013.[5] ## References[edit] 1. ^ a b c Abortion Policy - Slovenia 2. ^ ICMA - Laws on Abortion - Slovenia Archived 2010-07-10 at the Wayback Machine 3. ^ Historical abortion statistics, Slovenia 4. ^ "World Abortion Policies 2013". United Nations. 2013. Retrieved 3 March 2014. 5. ^ "Archived copy". Archived from the original on 2017-09-26. Retrieved 2017-09-28.CS1 maint: archived copy as title (link) * v * t * e Abortion in Europe Sovereign states * Albania * Andorra * Armenia * Austria * Azerbaijan * Belarus * Belgium * Bosnia and Herzegovina * Bulgaria * Croatia * Cyprus * Czech Republic * Denmark * Estonia * Finland * France * Georgia * Germany * Greece * Hungary * Iceland * Ireland * * Italy * Kazakhstan * Latvia * Liechtenstein * Lithuania * Luxembourg * Malta * Moldova * Monaco * Montenegro * Netherlands * North Macedonia * Norway * Poland * Portugal * Romania * Russia * San Marino * Serbia * Slovakia * Slovenia * Spain * Sweden * Switzerland * Turkey * Ukraine * United Kingdom * England * Northern Ireland * Scotland * Wales * Vatican City States with limited recognition * Abkhazia * Artsakh * Kosovo * Northern Cyprus * South Ossetia * Transnistria * v * t * e Abortion Main topics * Definitions * History * Methods * Abortion debate * Philosophical aspects * Abortion law Movements * Abortion-rights movements * Anti-abortion movements Issues * Abortion and mental health * Beginning of human personhood * Beginning of pregnancy controversy * Abortion-breast cancer hypothesis * Anti-abortion violence * Abortion under communism * Birth control * Crisis pregnancy center * Ethical aspects of abortion * Eugenics * Fetal rights * Forced abortion * Genetics and abortion * Late-term abortion * Legalized abortion and crime effect * Libertarian perspectives on abortion * Limit of viability * Malthusianism * Men's rights * Minors and abortion * Natalism * One-child policy * Paternal rights and abortion * Prenatal development * Reproductive rights * Self-induced abortion * Sex-selective abortion * Sidewalk counseling * Societal attitudes towards abortion * Socialism * Toxic abortion * Unsafe abortion * Women's rights By country Africa * Algeria * Angola * Benin * Botswana * Burkina Faso * Burundi * Cameroon * Cape Verde * Central African Republic * Chad * Egypt * Ghana * Kenya * Namibia * Nigeria * South Africa * Uganda * Zimbabwe Asia * Afghanistan * Armenia * Azerbaijan * Bahrain * Bangladesh * Bhutan * Brunei * Cambodia * China * Cyprus * East Timor * Georgia * India * Iran * Israel * Japan * Kazakhstan * South Korea * Malaysia * Nepal * Northern Cyprus * Philippines * Qatar * Saudi Arabia * Singapore * Turkey * United Arab Emirates * Vietnam * Yemen Europe * Albania * Andorra * Austria * Belarus * Belgium * Bosnia and Herzegovina * Bulgaria * Croatia * Czech Republic * Denmark * Estonia * Finland * France * Germany * Greece * Hungary * Iceland * Ireland * Italy * Kazakhstan * Latvia * Liechtenstein * Lithuania * Luxembourg * Malta * Moldova * Monaco * Montenegro * Netherlands * North Macedonia * Norway * Poland * Portugal * Romania * Russia * San Marino * Serbia * Slovakia * Slovenia * Spain * Sweden * Switzerland * Ukraine * United Kingdom North America * Belize * Canada * Costa Rica * Cuba * Dominican Republic * El Salvador * Guatemala * Mexico * Nicaragua * Panama * Trinidad and Tobago * United States Oceania * Australia * Micronesia * Fiji * Kiribati * Marshall Islands * New Zealand * Papua New Guinea * Samoa * Solomon Islands * Tonga * Tuvalu * Vanuatu South America * Argentina * Bolivia * Brazil * Chile * Colombia * Ecuador * Guyana * Paraguay * Peru * Suriname * Uruguay * Venezuela Law * Case law * Constitutional law * History of abortion law * Laws by country * Buffer zones * Conscientious objection * Fetal protection * Heartbeat bills * Informed consent * Late-term restrictions * Parental involvement * Spousal consent Methods * Vacuum aspiration * Dilation and evacuation * Dilation and curettage * Intact D&X * Hysterotomy * Instillation * Menstrual extraction * Abortifacient drugs * Methotrexate * Mifepristone * Misoprostol * Oxytocin * Self-induced abortion * Unsafe abortion Religion * Buddhism * Christianity * Catholicism * Hinduism * Islam * Judaism * Scientology * Category This abortion-related article is a stub. You can help Wikipedia by expanding it. * v * t * e This Slovenia-related article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports	Abortion in Slovenia	None	25,098	wikipedia	https://en.wikipedia.org/wiki/Abortion_in_Slovenia	2021-01-18T18:42:14	{"wikidata": ["Q4668493"]}
A number sign (#) is used with this entry because of evidence that a syndrome of microcephaly, seizures, spasticity, and brain calcifications (MISSBC) is caused by homozygous mutation in the PCDH12 gene (605622) on chromosome 5q31. Description MISSBC is an autosomal recessive neurodevelopmental disorder characterized by progressive microcephaly, early-onset seizures, and severely delayed or even absent psychomotor development with profound intellectual disability and spasticity or dystonia. Brain imaging shows midbrain dysplasia and intracerebral calcifications (summary by Aran et al., 2016). Clinical Features Tolmie et al. (1987) described a brother and sister with microcephaly with early-onset seizures and spasticity. Silengo et al. (1992) described a male-female sib pair, born of consanguineous parents, who had congenital microcephaly in association with early-onset myoclonic seizures, spasticity, and profound psychomotor retardation without detectable brain malformations. The severity of the neurologic features and their perinatal onset differentiated the syndrome from the more common autosomal recessive microcephaly. Gross-Tsur et al. (1995) described 5 microcephalic sibs, 4 females and 1 male, who were affected with neonatal generalized tonic-clonic seizures and went on to develop spastic quadriplegia and had essentially no psychomotor development. They were born to consanguineous parents of Arab extraction. All had profound mental retardation, and only 1 patient developed eye contact and a social smile. Chromosome analysis and CT scans were normal in all affected sibs but 1, in whom the CT showed absence of the anterior limbs of the internal capsule and a large caudate. There were 2 unaffected sibs, 1 male and 1 female, in this sibship. Sibs with the syndrome of microcephaly and severe myoclonic seizures, profound mental retardation, hypertonia, and spasticity were also described by Schinzel and Litschgi (1984). Straussberg et al. (1998) described an infant with the same syndrome born to a consanguineous couple of Palestinian origin. The findings of magnetic resonance imaging were reported. Straussberg et al. (1998) provided follow-up of a second patient who had previously been reported as suffering from Alpers disease (Frydman et al., 1993). The patient was born to first-cousin parents of Palestinian Arabs, the same ethnicity as the first patient of Straussberg et al. (1998). Two sibs had died of the same condition. Myoclonic and tonic-clonic seizures were first noted at the age of 10 days. Spasticity, swallowing difficulties, and frequent aspirations necessitated nasogastric feeding. EEG showed hypsarrhythmia. Aran et al. (2016) reported 10 patients from 4 consanguineous Palestinian families originating from the same small town with MISSBC. Three of the 10 were affected fetuses, each from a different family, who were terminated after prenatal ultrasound showed microcephaly and hyperechogenic foci in the perithalamic and/or periventricular regions. One fetus had midbrain dysplasia. Postmortem examinations were not performed on the fetuses. Two of the other patients were children, 1 of whom died at age 3 (family A) and the other who was alive but severely disabled at age 5 (family B). These patients had onset of seizures in the first days or weeks of life that were associated with multifocal or asynchronized epileptic discharges on EEG. The patients had axial hypotonia, peripheral dystonia with brisk reflexes, profound developmental disability, and visual impairment. Brain imaging of both children showed midbrain dysplasia; 1 also had hypoplasia of the corpus callosum. Aran et al. (2016) noted that the patients were investigated for possible intrauterine TORCH infections, but all tests were negative, with no evidence for infection. The third family (family C) had been reported by Gross-Tsur et al. (1995); only 1 affected individual was available for study. This was a 26-year-old woman with microcephaly (-7.5 SD), severe visual impairment, and severe psychomotor retardation. Other features included axial hypotonia, peripheral dystonia, and spasticity. Brain imaging was not performed. Her 4 older affected sibs had all died of pulmonary aspiration. Using CT imaging, Nicolas et al. (2017) determined that 1 of the patients reported by Aran et al. (2016) (patient III-1 from family B) had perithalamic calcifications in the posterior arms of the internal capsules and in the juxtacortical white matter. The findings confirmed that the hyperechogenicity observed by Aran et al. (2016) represented intracranial calcifications. Nicolas et al. (2017) noted that the expression pattern of PCDH12 is similar to that of SLC20A2 (158378), mutation in which causes idiopathic basal ganglia calcification-1 (IBGC1; 213600). Inheritance The transmission pattern of MISSBC in the families reported by Aran et al. (2016) was consistent with autosomal recessive inheritance. Molecular Genetics In 6 patients from 4 unrelated consanguineous Palestinian families with MISSBC, Aran et al. (2016) identified a homozygous truncating mutation in the PCDH12 gene (R839X; 605622.0001). The mutation was found by whole-genome sequencing and confirmed by Sanger sequencing in the first family, followed by direct sequencing in the subsequent families. It segregated with the disorder in all families. Haplotype analysis indicated a founder effect, and 3 of 83 unrelated healthy individuals from the same town carried the mutation, yielding a carrier rate of 0.018. Analysis of cells derived from 1 carrier indicated that the mutation results in nonsense-mediated mRNA decay and likely a complete loss of function. Nicolas et al. (2017) identified 4 different heterozygous missense variants in the PCDH12 gene in 4 of 79 patients with brain calcifications who were screened for mutations in the PCDH12 gene. All were found at very low frequencies in the ExAC database; functional studies of the variants, studies of patient cells, and segregation studies among family members were not performed. History In 2 ostensibly unrelated Jamaican black families living in Birmingham, England, Bundey and Hill (1975) found 3 cases of severe microcephaly with spastic quadriplegia beginning between 4 and 16 months of age. The authors concluded that Roboz and Pitt (1969) and perhaps others have reported the same condition. The paper by Bundey and Hill (1975) was not published, but the patients were referred to by Bundey and Griffiths (1977). The microcephaly was 'postnatal;' head circumference was normal at birth and at 7 months. There were no neonatal problems. The first abnormalities noted by the parents were unresponsiveness and delayed milestones. On reevaluation of the family, Bundey et al. (1991) concluded that the disorder may represent the Allan-Herndon syndrome (300523). INHERITANCE \- Autosomal recessive GROWTH Other \- Intrauterine growth retardation (IUGR) HEAD & NECK Head \- Microcephaly, progressive (up to -7.5 SD) Eyes \- Visual impairment, severe NEUROLOGIC Central Nervous System \- Delayed psychomotor development, profound \- Intellectual disability, profound \- Early-onset seizures \- Axial hypotonia \- Spastic quadriplegia \- Dystonia \- Hyperreflexia \- Early-onset seizures \- Midbrain-hypothalamus dysplasia \- Perithalamic and periventricular calcifications MISCELLANEOUS \- Onset in infancy MOLECULAR BASIS \- Caused by mutation in the protocadherin 12 gene (PCDH12, 605622.0001 ) ▲ 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	MICROCEPHALY, SEIZURES, SPASTICITY, AND BRAIN CALCIFICATIONS	c4538630	25,099	omim	https://www.omim.org/entry/251280	2019-09-22T16:25:10	{"omim": ["251280"]}

Subsets and Splits

No community queries yet

The top public SQL queries from the community will appear here once available.