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GMPPA-congenital disorder of glycosylation (GMPPA-CDG) is a rare disease, part of the group of congenital disorders of glycosylation. It is characterized by lack of tears (alacrima), difficulty in swallowing due to problems in the esophagus muscle (achalasia), and intellectual disability, starting at birth or in early infancy. More variable features include low muscle tone (hypotonia), gait abnormalities, differently sized pupils (anisocoria), and vision or hearing problems. The disorder is very similar to the triple A syndrome, but patients with AAMR do not have adrenal insufficiency. It is caused by a mutation in the GMPPA gene and is inherited in an autosomal recessive way. Treatment is directed to the symptoms and may involve using artificial tears, medication, balloon dilation or surgery to correct the defect in the esophagus, and physical therapy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	GMPPA-CDG	c3809738	28,500	gard	https://rarediseases.info.nih.gov/diseases/12404/gmppa-cdg	2021-01-18T18:00:14	{"omim": ["615510"], "synonyms": []}
A number sign (#) is used with this entry because ectodermal dysplasia-syndactyly syndrome-1 (EDSS1) is caused by homozygous or compound heterozygous mutation in the PVRL4 gene (NECTIN4; 609607) on chromosome 1q23. Description Ectodermal dysplasia-syndactyly syndrome (EDSS) is characterized by sparse to absent scalp hair, eyebrows, and eyelashes, hypoplastic nails, tooth enamel hypoplasia, conical-shaped teeth, palmoplantar keratoderma, and partial cutaneous syndactyly (summary by Raza et al., 2015). ### Genetic Heterogeneity of Ectodermal Dysplasia-Syndactyly Syndrome Ectodermal dysplasia-syndactyly syndrome-2 (EDSS2; 613576) maps to chromosome 7p21-p14. Clinical Features Brancati et al. (2010) studied 2 unrelated families displaying hair and teeth abnormalities associated with cutaneous syndactyly of the hands and/or feet. One family, originally described by Boudghene-Stambouli and Merad-Boudia (1991), had 4 affected sibs born to first-cousin, healthy Algerian parents. The other family had 2 affected sibs, born to nonconsanguineous healthy parents of Italian origin. All affected individuals manifested partial cutaneous syndactyly variably involving fingers 2-3 and 3-4 and toes 2-3 and 4-5. In the young patients, hair over the entire scalp was sparse and coarse, with a tendency to break at an early age. Eyebrows, eyelashes, and body hair showed identical abnormalities. Progressive hair loss manifested in the second decade of life with patchy areas of alopecia over the scalp and progressed toward complete alopecia. Hair morphologic abnormalities included twists at irregular intervals (pilli torti) and swelling along the shafts, particularly associated with areas of breakage. Dental findings consisted of abnormally widely spaced teeth, with peg-shaped and conical crowns. All patients had normal sweating. Jelani et al. (2011) reported a large 5-generation consanguineous family from a remote area of the Punjab province in Pakistan in which 10 individuals in the last generation had EDSS1. All had sparse scalp hair, sparse to absent eyebrows and eyelashes, conical and cylindrical teeth with enamel hypoplasia, hypoplastic nails, and cutaneous syndactyly of the third and fourth fingers and second and third toes. Most also had hyperkeratosis of the palms. None had hypo- or hyperhidrosis, cognitive impairment, or other systemic involvement. The clinical features in this family were similar to those described by Brancati et al. (2010), except that the hair did not show pili torti morphology. Fortugno et al. (2014) reported 3 sibs, born of first-cousin parents of Afghan origin, who had cutaneous syndactyly and hair and teeth abnormalities. All affected individuals showed abnormally widely spaced and hypoplastic teeth. Hair morphologic abnormalities included pili torti, and there was progressive hair loss that manifested in the second decade of life, resulting in complete alopecia. Cutaneous syndactyly was variable, but involved fingers 2 to 4 and toes 2 to 5. Intolerance to heat was reported in 1 affected individual. Raza et al. (2015) studied a large 5-generation consanguineous family, belonging to a tribe residing in a region at the border of India and Pakistan, in which 2 sibs and their first cousin once removed exhibited ectodermal dysplasia and syndactyly. All 3 presented a similar pattern of congenital hypotrichosis, with thin and sparse to absent scalp hair, sparse to absent eyebrows and eyelashes, and absent axillary and body hair; in the adult male patient, mustache and beard hair were missing. Light microscopy revealed a hair abnormality suggestive of pili torti. Severe dystrophic palmoplantar keratoderma was observed, and palm biopsy showed orthohyperkeratosis and complete absence of sweat gland units. Scalp biopsy showed epidermal hyperkeratosis and acanthosis, with a marked reduction in the density of hair follicles. Affected individuals had heat intolerance during summer months. Nails of hands and feet were thick, flat, and discolored, with longitudinal ridging and hyperkeratosis. Teeth were conical and cylindrical, with enamel hypoplasia. All 3 patients had partial cutaneous syndactyly up to the proximal interphalangeal joints involving fingers 2 to 4 and up to the distal interphalangeal joint involving toes 2 to 5. The patients also exhibited bilateral deformed pinnae, and all had purulent inflammation of the conjunctivae. Inheritance Brancati et al. (2010) demonstrated that ectodermal dysplasia-syndactyly syndrome-1 is an autosomal recessive disorder. Mapping In the consanguineous Algerian family with EDSS1 described by Boudghene-Stambouli and Merad-Boudia (1991), Brancati et al. (2010) used a homozygosity mapping approach to map the EDSS1 locus to chromosome 1q23.3 between SNPs rs11265404 and rs16833478 (112.6-158.6 Mb, NCBI36). Two-point linkage analysis gave a maximum lod score of 3.08 at D1S484. Molecular Genetics In affected members of the Algerian family with EDSS1 described by Boudghene-Stambouli and Merad-Boudia (1991), Brancati et al. (2010) identified a homozygous mutation in the PVRL4 gene (R284Q; 609607.0001). In affected members of an Italian family with EDSS1, they identified compound heterozygosity for mutations in the PVRL4 gene (T185M, 609607.0002; 906delT, 609607.0003). There was decreased PVRL4 immunostaining in the interfollicular epidermis and hair follicles of 1 patient. There was also highly disorganized cell membrane staining of alpha-catenin (CTNNA1; 116805), beta-catenin (CTNNB1; 116806), E-cadherin (CDH1; 192090), and afadin (MLLT4; 159559) in patient skin. In affected members of a consanguineous Pakistani family with EDSS1, Jelani et al. (2011) identified a homozygous mutation in the PVRL4 gene (P212R; 609607.0004). The mutation was found after homozygosity mapping identified linkage to chromosome 1q23. The findings implicated a role for cell adhesion molecules in the pathogenesis of the disorder. In 3 sibs with ectodermal dysplasia and cutaneous syndactyly, Fortugno et al. (2014) sequenced the PVRL4 gene and identified homozygosity for a missense mutation (V242M; 613753.0005) for which their unaffected parents were heterozygous. The authors noted clinical overlap between EDSS1 and cleft lip/palate-ectodermal dysplasia syndrome (CLPED1; 225060), caused by mutation in the PVRL1 gene (NECT1; 600644), and stated that the disorders could be referred to as 'nectinopathies.' In 3 affected members of a 5-generation consanguineous Pakistani family with EDSS mapping to chromosome 1q23, Raza et al. (2015) identified homozygosity for a nonsense mutation in the PVRL4 gene (Q61X; 609607.0006). The mutation was present in heterozygosity in the unaffected parents and sibs and was not found in 100 ethnically matched controls. INHERITANCE \- Autosomal recessive HEAD & NECK Teeth \- Peg-shaped teeth \- Conical crowns \- Enamel hypoplasia \- Widely-spaced teeth SKELETAL Hands \- Cutaneous syndactyly (3-4 and sometimes 2-3) Feet \- Cutaneous syndactyly (2-3 and sometimes 3-4) SKIN, NAILS, & HAIR Skin \- Hyperkeratosis, palmar \- Reduced or absent sweat glands (in some patients) Nails \- Hypoplastic fingernails \- Hypoplastic toenails \- Nail plate degeneration \- Thickened, discolored nails (in some patients) Hair \- Sparse scalp hair \- Coarse hair \- Pili torti \- Patchy alopecia \- Hair loss, progressive \- Sparse to absent eyebrows \- Sparse to absent eyelashes \- Absent facial hair (in some males) \- Sparse or absent body hair MISCELLANEOUS \- Heat intolerance (in some patients) MOLECULAR BASIS \- Caused by mutation in the poliovirus receptor-like 4 gene (PVRL4, 609607.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	ECTODERMAL DYSPLASIA-SYNDACTYLY SYNDROME 1	c3150807	28,501	omim	https://www.omim.org/entry/613573	2019-09-22T15:58:17	{"omim": ["613573"], "orphanet": ["247820"], "synonyms": ["EDSS", "EDSS1"]}
Disease of the feet of hooved animals Radiograph of a horse hoof showing rotation of the coffin bone and evidence of sinking, a condition often associated with laminitis. The annotation P2 stands for the middle phalanx, or pastern bone, and P3 denotes the distal phalanx, or coffin bone. The yellow lines mark the distance between the top and bottom part of the coffin bone relative to the hoof wall, showing the distal (bottom) of the coffin bone is rotated away from the hoof wall. Laminitis is a disease that affects the feet of ungulates and is found mostly in horses and cattle. Clinical signs include foot tenderness progressing to inability to walk, increased digital pulses, and increased temperature in the hooves. Severe cases with outwardly visible clinical signs are known by the colloquial term founder, and progression of the disease will lead to perforation of the coffin bone through the sole of the hoof or being unable to stand up, requiring euthanasia. ## Contents * 1 Laminae * 2 Pathophysiology * 2.1 Mechanism * 2.2 Theories of pathophysiology * 2.3 Rotation, sinking, and founder * 3 Phases of laminitis * 4 Causes * 4.1 Endotoxins * 4.2 Vasoactive amines * 4.3 Mechanical separation * 4.4 Poor blood circulation * 4.5 Complex causes * 5 Risk factors * 6 Diagnosis * 6.1 Clinical signs * 6.2 Lameness evaluation * 6.3 Radiographs * 6.4 Other diagnostics * 7 Prognosis * 8 Treatment * 8.1 Management * 8.2 Cryotherapy * 8.3 Drug therapies * 8.4 Trimming and shoeing * 8.5 Aggressive therapies * 9 Complications * 10 Informal use of the word "founder" * 11 See also * 12 References * 13 Further reading ## Laminae[edit] Main article: Horse hoof § Internal structures The bones of the hoof are suspended within the axial hooves of ungulates by layers of modified skin cells, known as laminae or lamellae, which act as shock absorbers during locomotion. In horses, there are about 550–600 pairs of primary epidermal laminae, each with 150–200 secondary laminae projection from their surface.[1] These interdigitate with equivalent structures on the surface of the coffin bone (PIII, P3, the third phalanx, pedal bone, or distal phalanx), known as dermal laminae.[2] The secondary laminae contain basal cells which attach via hemidesmosomes to the basement membrane. The basement membrane is then attached to the coffin bone via the connective tissue of the dermis.[1] ## Pathophysiology[edit] Laminitis literally means inflammation of the laminae, and while it remains controversial whether this is the primary mechanism of disease, evidence of inflammation occurs very early in some instances of the disease.[3] A severe inflammatory event is thought to damage the basal epithelial cells, resulting in dysfunction of the hemidesmosomes and subsequent reduction in adherence between the epithelial cells and the basement membrane.[4] Normal forces placed on the hoof are then strong enough to tear the remaining laminae, resulting in a failure of the interdigitation of the epidermal and dermal laminae between the hoof wall and the coffin bone. When severe enough, this results in displacement of the coffin bone within the hoof capsule.[4] Most cases of laminitis occur in both front feet, but laminitis may be seen in all four feet, both hind feet, or in cases of support limb laminitis, in a single foot.[4] ### Mechanism[edit] The mechanism remains unclear and is the subject of much research. Three conditions are thought to cause secondary laminitis: * Sepsis/endotoxemia or generalized inflammation * Endocrinopathy * Trauma: concussion or excessive weight-bearing Inflammation Inflammatory events that are associated with laminitis include sepsis, endotoxemia, retained placenta, carbohydrate overload (excessive grain or pasture), enterocolitis, pleuropneumonia, and contact with black walnut shavings.[5] In these cases, there is an increase in blood flow to the hoof, bringing in damaging substances and inflammatory cells into the hoof. Endocrinopathy Endocrinopathy is usually the result of improper insulin regulation, and is most commonly seen with pituitary pars intermedia dysfunction (also called equine Cushing's syndrome) and equine metabolic syndrome (EMS),[4] as well as obesity and glucocorticoid administration.[5] In cases of EMS, most episodes occur in the spring when the grass is lush.[4] Trauma Mechanical laminitis starts when the hoof wall is pulled away from the bone or lost, as a result of external influences. Mechanical laminitis can occur when a horse habitually paws, is ridden or driven on hard surfaces ("road founder"), or in cases of excessive weight-bearing due to compensation for the opposing limb, a process called support limb laminitis. Support limb laminitis is most common in horses suffering from severe injury to one limb, such as fracture, resulting in a non-weight bearing state that forces them to take excessive load on the opposing limb. This causes decreased blood flow to the cells, decreasing oxygen and nutrient delivery, and thus altering their metabolism which results in laminitis.[1] ### Theories of pathophysiology[edit] Matrix metalloproteinases One of the newest theories for the molecular basis of laminitis involves matrix metalloproteinases (MMPs). Metalloproteinases are enzymes that can degrade collagen, growth factors, and cytokines to remodel the extracellular matrix of tissues. To prevent tissue damage, they are regulated by tissue inhibitors of metalloproteinases (TIMPs). In cases of laminitis, an underlying cause is thought to cause an imbalance of MMPs and TIMPs, favoring MMPs, so that they may cleave substances within the extracellular matrix and therefore break down the basement membrane.[6] Since the basement membrane is the main link between the hoof wall and the connective tissue of P3, it is thought that its destruction results in their separation.[5] MMP-2 and MMP-9 are the primary enzymes thought to be linked to laminitis.[5] Theories for development There are multiple theories as to how laminitis develops. These include: * Enzymatic and inflammatory theories: The enzymatic theory postulates that increased blood flow to the foot brings in inflammatory cytokines or other substances to the hoof, where they increase production of MMPs, which subsequently break down the basement membrane. The inflammatory theory states that inflammatory mediators produce inflammation, but recognizes that MMP production occurs later. Therefore, this is possibly a 2-step process, beginning with inflammation and leading to MMP production and subsequent laminitis.[5] * Vascular theory: Postulates that increases in capillary pressure, constriction of veins, and shunting of blood through anastomoses to bypass the capillaries, causes decreased blood and therefore decreased oxygen and nutrient delivery to lamellae. The end-result would be ischemia, leading to cellular death and breakdown between the lamellae. Subsequently, increased vascular permeability leads to edema within the hoof, compression of small vessels, and ischemia. Vasoactive amines may be partially to blame for changes in hoof blood flow.[5] * Metabolic theory: Insulin affects multiple processes within the body, including inflammation, blood flow, and tissue remodeling. Change in insulin regulation may lead to laminitis.[5] Hyperinsulinemia has been shown to cause increased length of the secondary lamellae and epidermal cell proliferation.[1] * Traumatic theory: Concussion is thought to directly damage lamellae, and increased weight-bearing is thought to decrease blood supply to the foot.[5] ### Rotation, sinking, and founder[edit] Hoof sagittal section with massive inflammation and rotation of third phalanx. Normally, the front of the third phalanx is parallel to the hoof wall and its lower surface should be roughly parallel to the ground surface. A single severe laminitic episode or repeated, less severe episodes can, depending upon the degree of separation of dermal and epidermal laminae, lead to either rotation or sinking of the pedal bone, both of which result in anatomical changes in the position of the coffin bone with visible separation of the laminae, colloquially known as founder. Rotation and distal displacement may occur in the same horse.[4] Both forms of displacement may lead to the coffin bone penetrating the sole. Penetration of the sole is not inherently fatal; many horses have been returned to service by aggressive treatment by a veterinarian and farrier, but the treatment is time-consuming, difficult and expensive. Rotation is the most common form of displacement, and, in this case, the tip of the coffin bone rotates downward.[4] The degree of rotation may be influenced by the severity of the initial attack and the time of initiation and aggressiveness of treatment. A combination of forces (e.g. the tension of the deep digital flexor tendon and the weight of the horse) result in the deep digital flexor tendon literally pulling the dorsal face of the coffin bone away from the inside of the hoof wall, which allows the coffin bone to rotate. Also, ligaments attaching the collateral cartilages to the digit, primarily in the palmar portion of the foot, possibly contribute to a difference in support from front to back. The body weight of the animal probably contributes to rotation of the coffin bone. Rotation results in an obvious misalignment between PII (the short pastern bone) and PIII (the coffin bone). If rotation of the third phalanx continues, its tip can eventually penetrate the sole of the foot. Sinking is less common and much more severe. It results when a significant failure of the interdigitation between the sensitive and insensitive laminae around a significant portion of the hoof occurs. The destruction of the sensitive laminae results in the hoof wall becoming separated from the rest of the hoof, so that it drops within the hoof capsule. Sinking may be symmetrical, i.e., the entire bone moves distally, or asymmetric, where the lateral or medial aspect of the bone displaces distally.[4] Pus may leak out at the white line or at the coronary band. In extreme cases, this event allows the tip to eventually penetrate the sole of the foot. A severe "sinker" usually warrants the gravest prognosis and may, depending upon many factors, including the quality of aftercare, age of the horse, diet and nutrition, skill, and knowledge and ability of the attending veterinarian and farrier(s), lead to euthanasia of the patient. ## Phases of laminitis[edit] Treatment and prognosis depend on the phase of the disease, with horses treated in earlier stages often having a better prognosis. Developmental phase The developmental phase is defined as the time between the initial exposure to the causative agent or incident, until the onset of clinical signs. It generally lasts 24–60 hours, and is the best time to treat a laminitis episode. Clinical laminitis may be prevented if cryotherapy (icing) is initiated during the developmental phase.[1] Acute phase The acute phase is the first 72 hours following the initiation of clinical signs. Treatment response during this time determines if the horse will go into the subacute phase or chronic phase. Clinical signs at this time include bounding digital pulses, lameness, heat, and possibly response to hoof testing.[1] Subacute phase The subacute phase occurs if there is minimal damage to the lamellae. Clinical signs seen in the acute phase resolve, and the horse becomes sound. The horse never shows radiographic changes, and there is no injury to the coffin bone.[1] Chronic phase Hoof specimen, sagittal section. Severe P3 rotation and penetration into the sole. A lamellar wedge is evident. The chronic phase occurs if damage to the lamellae is not controlled early in the process, so that the coffin bone displaces. Changes that may occur include separation of the dermal and epidermal lamellae, lengthening of the dermal lamellae, and compression of the coronary and solar dermis. If laminitis is allowed to continue, long-term changes such as remodeling of the apex and distal border of the coffin bone (so that a "lip" develops) and osteolysis of the coffin bone can occur.[1] The chronic phase may be compensated or uncompensated. Compensated cases will have altered hoof structure, including founder rings, wide white lines, and decreased concavity to the sole. Horses will be relatively sound. On radiographs, remodeling of the coffin bone and in cases of rotational displacement, the distal hoof wall will be thicker than that proximally. Venograms will have relatively normal contrast distribution, including to the apex and distal border of the coffin bone, and the coronary band, but "feathering" may be present at the lamellar "scar."[1] Uncompensated cases will develop a lamellar wedge (pathologic horn), leading to a poor bridge between P3 and the hoof capsule. This will lead to irregular horn growth and chronic lameness, and horses will suffer from laminitis "flares." Inappropriate hoof growth will occur: the dorsal horn will have a tendency to grow outward rather than down, the heels will grow faster than the toe, and the white line will widen, leading to a potential space for packing of debris. The solar dermis is often compressed enough to inhibit growth, leading to a soft, thin sole (<10 mm) that may develop seromas. In severe cases where collapse of the suspensory apparatus of P3 has occurred, the solar dermis or the tip of P3 may penetrate the sole. The horse will also be prone to recurrent abscessation within the hoof capsule. Venogram will show "feathering" into the vascular bed beneath the lamellae, and there will be decreased or absent contrast material in the area distal to the apex of the coffin bone.[1] ## Causes[edit] The front feet of this horse exhibit the rings and overgrowth typical of foundered horses Laminitis has multiple causes, some of which commonly occur together. These causes can be grouped into broad categories. ### Endotoxins[edit] * Carbohydrate overload: One of the more common causes, current theory states[citation needed] that if a horse is given grain in excess or eats grass under stress and has accumulated excess nonstructural carbohydrates (sugars, starch, or fructan), it may be unable to digest all of the carbohydrate in the foregut. The excess then moves on to the hindgut and ferments in the cecum. The presence of this fermenting carbohydrate in the cecum causes proliferation of lactic acid bacteria and an increase in acidity. This process kills beneficial bacteria, which ferment fiber. The endotoxins and exotoxins may then be absorbed into the bloodstream, due to increased gut permeability, caused by irritation of the gut lining by increased acidity. The result is body-wide inflammation, but particularly in the laminae of the feet, where swelling tissues have no place to expand without injury to other structures. This results in laminitis. * Nitrogen compound overload: Herbivores are equipped to deal with a normal level of potentially toxic nonprotein nitrogen compounds in their forage. If, for any reason, rapid increases in levels of these compounds occur, for instance in lush spring growth on fertilized lowland pasture, the natural metabolic processes can become overloaded, resulting in liver disturbance and toxic imbalance. For this reason, many avoid using synthetic nitrogen fertilizer on horse pasture. If clover (or any legume) is allowed to dominate the pasture, this may also allow excess nitrogen to accumulate in forage, under stressful conditions such as frost or drought. Many weeds eaten by horses are nitrate accumulators. Direct ingestion of nitrate fertilizer material can also trigger laminitis, by a similar mechanism. * Colic: Laminitis can sometimes develop after a serious case of colic, due to the release of endotoxins into the blood stream. * Lush pastures: When releasing horses back into a pasture after being kept inside (typically during the transition from winter stabling to spring outdoor keeping), the excess fructan of fresh spring grass can lead to a bout of laminitis. Ponies and other easy keepers are much more susceptible to this form of laminitis than are larger horses. * Frosted grass: Freezing temperatures in the fall also coincide with outbreaks of laminitis in horses at pasture. Lower temperatures cause growth to cease, so sugar in pasture grasses cannot be used by the plant as fast as it is produced, thus they accumulate in the forage. Cool-season grasses form fructan, and warm season grasses form starch.[7] Sugars cause increases in insulin levels, which are known to trigger laminitis. Fructan is theorized to cause laminitis by causing an imbalance of the normal bowel flora leading to endotoxin production. These endotoxins may exacerbate insulin resistance, or the damage to the lining of the gut may release other as yet unidentified trigger factors into the blood stream. For horses prone to laminitis, restrict or avoid grazing when night temperatures are below 40 °F (5 °C) followed by sunny days. When growth resumes during warmer weather, sugar will be used to form protein and fiber and will not accumulate. * Untreated infections: Systemic infections, particularly those caused by bacteria, can cause release of endotoxins into the blood stream. A retained placenta in a mare (see below) is a notorious cause of laminitis and founder. * Insulin resistance: Laminitis can also be caused by insulin resistance in the horse. Insulin-resistant horses tend to become obese very easily and, even when starved down, may have abnormal fat deposits in the neck, shoulders, loin, above the eyes, and around the tail head, even when the rest of the body appears to be in normal condition. The mechanism by which laminitis associated with insulin resistance occurs is not understood, but may be triggered by sugar and starch in the diet of susceptible individuals. Ponies and breeds that evolved in relatively harsh environments, with only sparse grass, tend to be more insulin-resistant, possibly as a survival mechanism. Insulin-resistant animals may become laminitic from only very small amounts of grain or "high sugar" grass. Slow adaptation to pasture is not effective, as it is with laminitis caused by microbial population upsets. Insulin-resistant horses with laminitis must be removed from all green grass and be fed only hay tested for nonstructural carbohydrates (sugar, starch and fructan) and found to be below 11% on a dry-matter basis. See also: Equine metabolic syndrome ### Vasoactive amines[edit] The inflammatory molecule histamine has also been hypothesized as a causative agent of laminitis.[8][9] However, contradictory evidence indicates the role of histamine in laminitis has not been conclusively established.[10] ### Mechanical separation[edit] See also: § Mechanical laminitis Commonly known as road founder, mechanical separation occurs when horses with long toes are worked extensively on hard ground. The long toes and hard ground together contribute to delayed breakover, hence mechanical separation of the laminae at the toe. Historically, this was seen in carriage horses bred for heavy bodies and long, slim legs with relatively small hooves; their hooves were trimmed for long toes (to make them lift their feet higher, enhancing their stylish "action"), and they were worked at speed on hard roads. Road founder is also seen in overweight animals, particularly when hooves are allowed to grow long; classic examples are ponies on pasture board in spring, and pregnant mares.[11] ### Poor blood circulation[edit] Normal blood circulation in the lower limbs of a horse depends in part on the horse moving about. Lack of sufficient movement, alone or in combination with other factors, can cause stagnant anoxia, which in turn can cause laminitis.[11] A horse favoring an injured leg will both severely limit its movement and place greater weight on the other legs. This sometimes leads to static laminitis, particularly if the animal is confined in a stall.[11] A notable example is the 2006 Kentucky Derby winner Barbaro.[12] Transport laminitis sometimes occurs in horses confined in a trailer or other transportation for long periods of time. Historically, the most extreme instances were of horses shipped overseas on sailing ships. However, the continual shifting of weight required to balance in a moving vehicle may enhance blood circulation, so some horsemen recommend trailering as an initial step in rehabilitation of a horse after long confinement.[citation needed] Laminitis has been observed following an equine standing in extreme conditions of cold, especially in deep snow.[citation needed] Laminitis has also followed prolonged heating such as may be experienced from prolonged contact with extremely hot soil or from incorrectly applied hot-shoeing.[citation needed] ### Complex causes[edit] * Pituitary pars intermedia dysfunction, or Cushing's disease, is common in older horses and ponies and causes an increased predisposition to laminitis. * Equine metabolic syndrome is a subject of much new research and is increasingly believed to have a major role in laminitis. It involves many factors such as cortisol metabolism and insulin resistance. It has some similarities to type II diabetes in humans. In this syndrome, peripheral fat cells synthesise adipokines which are analogous to cortisol, resulting in Cushings-like symptoms. * A retained placenta, if not passed completely after the birth of a foal, can cause mares to founder, whether through toxicity, bacterial fever, or both. * Anecdotal reports of laminitis following the administration of drugs have been made, especially in the case of corticosteroids. The reaction may be an expression of idiosyncrasy in a particular patient, as many horses receive high dose glucocorticoid into their joints without showing any evidence of clinical laminitis.[13] [14] * Even horses not considered to be susceptible to laminitis can become laminitic when exposed to certain agrichemicals. The most commonly experienced examples are certain herbicides and synthetic nitrate fertilizer. ## Risk factors[edit] Whilst diet has long been known to be linked to laminitis, there is emerging evidence that breed and body condition also play a role.[15] Levels of hormones, particularly adiponectin, and serum insulin are also implicated, opening up new possibilities for developing early prognostic tests and risk assessments.[16] ## Diagnosis[edit] Early diagnosis is essential to effective treatment. However, early outward signs may be fairly nonspecific. Careful physical examination typically is diagnostic, but radiographs are also very useful. ### Clinical signs[edit] Cross-section of horse with severe laminitis, showing a dished dorsal hoof wall that grows in a more horizontal manner, and a sole that is convex due to pressure from the tip of P3 secondary to rotation. * Increased temperature of the wall, sole and/or coronary band of the foot[4] * A pounding pulse in the digital palmar artery[4] * Anxiety and visible trembling * Increased vital signs and body temperature * Sweating * Flared nostrils * Walking very tenderly, as if walking on egg shells * Repeated "easing" of affected feet, i.e. constant shifting of weight * Lameness with a positive response to hoof testers at the toe[4] * The horse stands in a "founder stance" in attempt to decrease the load on the affected feet. If it has laminitis in the front hooves, it will bring its hind legs underneath its body and put its fore legs out in front.[4] In cases of sinking, the horse stands with all four feet close together, like a circus elephant. * Tendency to lie down whenever possible, and recumbency in extreme cases[4] * Change in the outward appearance of the hoof in cases of chronic laminitis: dished (concave) dorsal hoof wall, "founder rings" (growth rings that are wider at the heel than the toe), a sole that is either flat or convex just dorsal to the apex of the frog which indicates P3 has displaced or penetrated, widening of the white line at the toe with or without bruising, "clubbing" of the foot.[1][4] * Change in the appearance of the coronary band: hair that does not lie in a normal position (not against the hoof wall), indentation or rim just above the hoof capsule allowing palpation behind the coronary band.[1] * In cases of sinking, it may be possible to palpate a groove between the coronary band and the skin of the pastern.[4] ### Lameness evaluation[edit] Hoof testing Laminitic horses are generally sore to pressure from hoof testers applied over the toe area. However, there is risk of a false negative if the horse naturally has a thick sole, or if the hoof capsule is about to slough.[1] Obel grading system The severity of lameness is qualified using the Obel grading system:[17] * Obel grade 1: Horse shifts weight between affected feet or continuously lifts feet up. It is sound at the walk but displays a shortened stride at the trot. * Obel grade 2: Horse displays a stilted, stiff gait, although is willing to walk. It is possible to easily lift a front foot and have the horse take all of its weight on the contralateral limb. * Obel grade 3: Horse displays a stilted, stiff gait, but is reluctant to walk and is difficult when asked to lift a front foot. * Obel grade 4: Horse is very reluctant to move, or is recumbent. Nerve blocks Horses suffering from the disease usually require an abaxial sesamoid block to relieve them of pain, since the majority of pain comes from the hoof wall. However, chronic cases may respond to a palmar digital block since they usually have primarily sole pain.[4] Severe cases may not respond fully to nerve blocks.[1] ### Radiographs[edit] Radiographs are an important part of evaluating the laminitic horse. They not only allow the practitioner to determine the severity of the episode, which does not always correlate with degree of pain,[1] but also to gauge improvement and response to treatment. Several measurements are made to predict severity. Additionally, radiographs also allow the visualization and evaluation of the hoof capsule, and can help detect the presence of a lamellar wedge or seromas.[1] The lateral view provides the majority of the information regarding degree of rotation, sole depth, dorsal hoof wall thickness, and vertical deviation.[1][18] A 65-degree dorsopalmar view is useful in the case of chronic laminitis to evaluate the rim of the coffin bone for pathology.[1] Radiographic measurements Radiographic measurements, including coronary extensor distance (CE), horn:lamellar distance (HL), sole depth (SD), digital breakover (DB), and palmar angle (PA) Several radiographic measurements, made on the lateral view, allow for objective evaluation of the episode. 1. Coronary extensor distance (CE): the vertical distance from the level of the proximal coronary band to the extensor process of P3. It is often used to compare progression of the disease over time, rather than as a stand-alone value. A rapidly increasing CE value can indicate distal displacement (sinking) of the coffin bone, while a more gradual increase in CE can occur with foot collapse. Normal values range from 0–30 mm, with most horses >12–15 mm.[1] 2. Sole depth (SD): the distance from the tip of P3 to the ground. 3. Digital breakover (DB): distance from the tip of P3 to the breakover of the hoof (dorsal toe).[1] 4. Palmar angle (PA): the angle between a line perpendicular to the ground, and a line at the angle of the palmar surface of P3. 5. Horn:lamellar distance (HL): the measurement from the most superficial aspect of the dorsal hoof wall to the face of P3. 2 distances are compared: a proximal measurement made just distal to the extensor process of P3, and a distal measurement made toward the tip of P3. These two values should be similar. In cases of rotation, the distal measurement will be higher than the proximal. In cases of distal displacement, both values will increase, but may remain equal. Therefore, it is ideal to have baseline radiographs for horses, especially for those at high-risk for laminitis, to compare to should laminitis ever be suspected. Normal HL values vary by breed and age:[1] * * * Weanlings will have a greater proximal HL compared to distal HL * Yearlings will have approximately equal proximal and distal HL * Thoroughbreds are usually 17mm proximally, and 19mm distally * Standardbreds have been shown to have a similar proximal and distal HL, around 16 mm at 2 years old, and 20 mm at 4 years old * Warmbloods have similar proximal and distal values, up to 20 mm each * HL tends to increase with age, up to 17 mm in most light breeds, or higher, especially in very old animals Venograms Venograms can help determine the prognosis for the animal, particularly in horses where the degree of pain does not match the radiographic changes. In venography, a contrast agent, visible on radiographs, is injected into the palmar digital vein to delineate the vasculature of the foot.[1] The venogram can assess the severity and location of tissue compromise and monitor effectiveness of the current therapy.[18] Compression of veins within the hoof will be seen as sections that do not contain contrast material. Poor or improper blood flow to different regions of the hoof help determine the severity of the laminitic episode. Venography is especially useful for early detection of support limb laminitis, as changes will be seen on venograph (and MRI) within 1–2 weeks, whereas clinical signs and radiographic changes do not manifest until 4–6 weeks.[1] Horses undergoing venography have plain radiographs taken beforehand to allow for comparison. The feet are blocked to allow the sedated horse to stand comfortably during the procedure. Prior to injection, a tourniquet is placed around the fetlock to help keep the contrast material within the foot during radiography. Diffusion of contrast may make some areas appear hypoperfused, falsely increasing the apparent severity of the laminitic episode. After injection of the contrast material, films are taken within 45 seconds to avoid artifact caused by diffusion. Evaluation of blood supply to several areas of the foot allows the practitioner to distinguish mild, moderate, and severe compromise of the hoof, chronic laminitis, and sinking.[1] ### Other diagnostics[edit] Other imaging tools have been used to show mechanical deviations in laminitis cases include computed tomography, as well as MRI, which also provides some physiologic information.[citation needed] Nuclear scintigraphy may also be useful in certain situations. Ultrasonography has been explored as a way to quantify changes in bloodflow to the foot.[19] ## Prognosis[edit] The sooner the diagnosis is made, the faster the treatment and the recovery process can begin. Rapid diagnosis of laminitis is often difficult, since the general problem often starts somewhere else in the horse's body. With modern therapies, most laminitics will be able to bear a rider or completely recover, if treated quickly, and if the laminitis was not severe or complicated (e.g. by equine metabolic syndrome or Cushing's disease). Even in these cases, a clinical cure can often be achieved. Endotoxic laminitis (e.g. after foaling) tends to be more difficult to treat. Successful treatment requires a competent farrier and veterinarian, and success is not guaranteed. A horse can live with laminitis for many years, and although a single episode of laminitis predisposes to further episodes, with good management and prompt treatment it is by no means the catastrophe sometimes supposed: most horses suffering an acute episode without pedal bone displacement make a complete functional recovery. Some countermeasures can be adopted for pasture based animals.[20][21] Discovery of laminitis, either active or relatively stabilized, on an equine prepurchase exam typically downgrades the horse's value, as the possibility of recurrence is a significant risk factor for the future performance of the horse. Several radiographic abnormalities can be judged to correlate with a worsened prognosis: * Increased degree of rotation of P3 relative to the dorsal hoof wall (rotation greater than 11.5 degrees has a poorer prognosis)[4] * Increased founder distance, the vertical distance from the coronary band (seen with a radio-opaque marker) to the dorsoproximal aspect of P3 (distance greater than 15.2mm has a poorer prognosis)[4] * Decreased sole depth[4] * Sole penetration by P3 ## Treatment[edit] In laminitis cases, a clear distinction must be made between the acute onset of a laminitis attack and a chronic situation. A chronic situation can be either stable or unstable. The difference between acute, chronic, stable, and unstable is of vital importance when choosing a treatment protocol. There is no cure for a laminitic episode and many go undetected. Initial treatment with cryotherapy and anti-inflammatory drugs may prevent mechanical breakdown if instituted immediately, but many cases are only detected after the initial microscopic damage has been done.[citation needed] In cases of sepsis or endotoxemia, the underlying cause should be addressed concurrently with laminitis treatment.[4] There are various methods for treating laminitis, and opinions vary on which are most useful. Additionally, the each horse and affected hoof should be evaluated individually to determine the best treatment plan, which may change with time.[1] Ideally, affected hooves are re-evaluated on a regular basis once treatment commences to track progress.[1] ### Management[edit] Initial management usually includes stall rest to minimize movement, and deeply bedding the stall with shavings, straw, or sand. Exercise is slowly increased once the horse has improved, ideally in an area with good (soft) footing, beginning with hand-walking, then turn-out, and finally riding under saddle.[1] This process may take months to complete.[1] ### Cryotherapy[edit] Cooling of the hoof in the developmental stages of laminitis has been shown to have a protective effect when horses are experimentally exposed to carbohydrate overload. Feet placed in ice slurries were less likely to experience laminitis than "uniced" feet.[22] Cryotherapy reduces inflammatory events in the lamellae. Ideally, limbs should be placed in an ice bath up to the level of the knee or hock. Hooves need to be maintained at a temperature less than 10 degrees Celsius at the hoof wall, for 24–72 hours.[1] In the case of a full-blown case of laminitis, use of a cold water spa proved effective in the treatment of Bal a Bali. For the first three days, Bal a Bali was kept in the spa for eight hours at a time. Once his condition stabilized, he continued to be put in the spa twice a day over the next few months.[23] ### Drug therapies[edit] Anti-inflammatories and analgesics Anti-inflammatories are always used when treating acute case of laminitis, and include Nonsteroidal anti-inflammatory medications (NSAIDS), DMSO, pentoxpfylline, and cryotherapy.[4] For analgesia, NSAIDs are often the first line of defense. Phenylbutazone is commonly used for its strong effect and relatively low cost. Flunixin (Banamine), ketofen, and others are also used. Nonspecific NSAIDs such as suxibuzone, or COX-2-specific drugs, such as firocoxib and diclofenac, may be somewhat safer than phenylbutazone in preventing NSAID toxicity such as right dorsal colitis, gastric ulcers, and kidney damage.[24][25][26] However, firocoxib provides less pain relief than phenylbutazone or flunixin.[1] Care must be taken that pain is not totally eliminated, since this will encourage the horse to stand and move around, which increases mechanical separation of the laminae.[1] Pentafusion, or the administration of ketamine, lidocaine, morphine, detomidine, and acepromazine at a constant rate of infusion, may be of particular benefit to horses suffering from laminitis.[4] Epidurals may also be used in hind-limb laminitis.[4] Vasodilators Vasodilators are often used with the goal of improving laminar blood flow. However, during the developmental phases of laminitis, vasodilation is contraindicated, either through hot water or vasodilatory drugs.[27] Systemic acepromazine as a vasodilator with the fringe benefit of mild sedation which reduces the horse/pony's movements and thus reduces concussion on the hooves, may be beneficial after lamellar damage has occurred, although no effects on laminar blood flow with this medication have been shown.[28] Nitroglycerine has also been applied topically in an attempt to increase blood flow, but this treatment does not appear to be an effective way to increase blood flow in the equine digit.[29] ### Trimming and shoeing[edit] Besides pain management and control of any predisposing factors, mechanical stabilization is a primary treatment goal once the initial inflammatory and metabolic issues have resolved. No approach has been shown to be effective in all situations, and debate is ongoing the merits and faults of the numerous techniques. Once the distal phalanx rotates, it is essential to derotate and re-establish its proper spatial orientation within the hoof capsule, to ensure the best long-term prospects for the horse. With correct trimming and, as necessary, the application of orthotics, one can effect this reorientation. However, this is not always completely effective. Trimming Successful treatment for any type of founder must necessarily involve stabilization of the bony column by some means. Correct trimming can help improve stabilization. This usually includes bringing the "break over" back to decrease the fulcrum-effect that stresses the laminae. Trimming the heels helps to ensure frog pressure and increases surface area for weight-bearing on the back half of the hoof.[1] While horses may stabilize if left barefooted, some veterinarians believe the most successful methods of treating founder involve positive stabilisation of the distal phalanx, by mechanical means, e.g., shoes, pads, polymeric support, etc. Pour-in pads or putty is sometimes placed on the sole to increase surface area for weight-bearing, so that the sole in the area of the quarters, and the bars, will take some of the weight.[1] Altering the palmar angle The deep digital flexor tendon places a constant pull on the back of the coffin bone. This is sometimes counteracted by decreasing the palmar angle of the hoof by raising the heels, often with the use of special shoes which have a wedge in the heel of approximately 20 degrees. Shoes are usually glued or cast onto the foot so painful nailing does not have to take place. The position of P3 within the hoof is monitored with radiographs. Once the horse has improved, the wedge of the shoe must be slowly reduced back to normal.[1] Use of orthotics The application of external orthotic devices to the foot in a horse with undisplaced laminitis and once displacement has occurred is widespread. Most approaches attempt to shift weight away from the laminae and onto secondary weight-bearing structures, while sparing the sole. Corrective hoof trimming Corrective hoof trimming will restore proper hoof form and function. Corrective trimming will allow the hooves to be healthy again. Realigning trimming Realigning trimming trims back the toe so that it is in line with the coffin bone. Realigning trimming pushes the coffin bone back into the correct position. The process of a new hoof capsule totally growing out to replace the old one takes up to a year. ### Aggressive therapies[edit] Dorsal hoof wall resection A dorsal hoof wall resection may help in certain conditions after consultation with an experienced veterinarian and farrier team. If decreased bloodflow distal to the coronary plexus is seen on a venogram, or when a laminar wedge forms between P3 and the hoof wall, preventing the proper reattachment (interdigitation) of the laminae, this procedure may be beneficial. When the coffin bone is pulled away from the hoof wall, the remaining laminae will tear. This may lead to abscesses within the hoof capsule that can be severe and very painful, as well as a mass of disorganized tissue called a laminar (or lamellar) wedge.[30] Coronary grooving Coronary grooving involves removing a groove of hoof wall just distal to the coronary band. It is thought to encourage dorsal hoof wall growth and improve alignment of the wall.[4] Deep digital flexor tenotomy Main article: Treatment of equine lameness § Deep digital flexor tendon tenotomy Because the rotation of P3 is exacerbated by continued pull on the deep digital flexor tendon, one approach to therapy has been to cut this tendon, either in the cannon region (mid-metacarpus)[4] or in the pastern region. Over a time period of 6 weeks, tenotomy is thought to allow P3 to realign with the ground surface.[4] Critics claim that this technique is unsuccessful and invasive, with advocates making counter-arguments that it is often used in cases which are too far advanced for treatment to help.[31] Tenotomy does risk subluxation of the distal interphalangeal joint (coffin joint),[4] which may be avoided with the use of heel extensions on the shoe.[1] Horses may return to work after the surgery.[1] This treatment is often recommended for severe cases of laminitis, and requires proper trimming and shoeing to be successful.[1] Botulinum toxin infusion As an alternative to the deep digital flexor tenotomy, Clostridium botulinum type A toxin has been infused into the body of the deep digital flexor muscle. This theoretically allows for the same derotation as a tenotomy, but without the potential for scarring or contracture associated with that procedure. A recent study used this technique in seven laminitic horses. Significant improvement was seen in six of the horses, with moderate improvement in the seventh.[32] ## Complications[edit] Complications to laminitis include recurrent hoof abscesses, which are sometimes secondary to pedal osteitis,[1] seromas, and fractures to the solar margin of the coffin bone.[4] ## Informal use of the word "founder"[edit] Informally, particularly in the United States, "founder" has come to mean any chronic changes in the structure of the foot that can be linked to laminitis. In some texts, the term is even used synonymously with laminitis, though such usage is technically incorrect. Put simply, not all horses that experience laminitis will founder, but all horses that founder will first experience laminitis. ## See also[edit] * Barefoot horses * Farrier * Horse hoof * Horseshoe * Lameness (equine) ## References[edit] 1. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al Orsini J, Divers T (2014). Equine Emergencies (4th ed.). St. Louis, MO: Elsevier. pp. 697–712. ISBN 978-1-4557-0892-5. 2. ^ Pollitt CC (1995). Color Atlas of the Horse's Foot. Mosby. ISBN 978-0-7234-1765-1. 3. ^ Loftus JP, Black SJ, Pettigrew A, Abrahamsen EJ, Belknap JK (November 2007). "Early laminar events involving endothelial activation in horses with black walnut- induced laminitis". American Journal of Veterinary Research. 68 (11): 1205–11. doi:10.2460/ajvr.68.11.1205. PMID 17975975. 4. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab Baxter G (2011). Manual of Equine Lameness (1st ed.). Ames, Iowa: Wiley-Blackwell. pp. 257–262. ISBN 978-0-8138-1546-6. 5. ^ a b c d e f g h Huntington P, Pollitt C, McGowan C (September 2009). "Recent research into laminitis" (PDF). Advances in Equine Nutrition. IV: 293. Archived from the original (PDF) on 23 March 2013. Retrieved 28 July 2014. 6. ^ de Laat MA, Kyaw-Tanner MT, Nourian AR, McGowan CM, Sillence MN, Pollitt CC (April 2011). "The developmental and acute phases of insulin-induced laminitis involve minimal metalloproteinase activity" (PDF). Veterinary Immunology and Immunopathology. 140 (3–4): 275–81. doi:10.1016/j.vetimm.2011.01.013. PMID 21333362. 7. ^ Watts KA (March 2004). "Forage and Pasture Management for Laminitic Horses" (PDF). Clinical Techniques in Equine Practice. 3 (1): 88–95. doi:10.1053/j.ctep.2004.07.009. Archived (PDF) from the original on 2010-12-31. Retrieved 2010-04-22. 8. ^ Nilsson SA (1963). "Clinical, morphological and experimental studies of laminitis in cattle". Acta Veterinaria Scandinavica. 4 (Suppl. 1): 188–222. OCLC 13816616. 9. ^ Takahashi K, Young BA (June 1981). "Effects of grain overfeeding and histamine injection on physiological responses related to acute bovine laminitis". Nihon Juigaku Zasshi. The Japanese Journal of Veterinary Science. 43 (3): 375–85. doi:10.1292/jvms1939.43.375. PMID 7321364. 10. ^ Thoefner MB, Pollitt CC, Van Eps AW, Milinovich GJ, Trott DJ, Wattle O, Andersen PH (September 2004). "Acute bovine laminitis: a new induction model using alimentary oligofructose overload". Journal of Dairy Science. 87 (9): 2932–40. doi:10.3168/jds.s0022-0302(04)73424-4. PMID 15375054. 11. ^ a b c Rooney J. "Nonclassical laminitis". Archived from the original on 2008-01-24. 12. ^ "Transcript of Press Conference on the condition of Barbaro" (PDF). University of Pennsylvania School of Veterinary Medicine. 13 July 2006. Archived from the original (PDF) on 4 February 2007. 13. ^ McCluskey, M. J.; Kavenagh, P. B. (2010). "Clinical use of triamcinolone acetonide in the horse (205 cases) and the incidence of glucocorticoid‐induced laminitis associated with its use". Equine Veterinary Education. 16 (2): 86–89. doi:10.1111/j.2042-3292.2004.tb00272.x. 14. ^ "No Evidence That Therapeutic Systemic Corticosteroid Administration is Associated With Laminitis in Adult Horses Without Underlying Endocrine or Severe Systemic Disease". 15. ^ Luthersson N, Mannfalk M, Parkin TD, Harris P (2017). "Laminitis: Risk Factors and Outcome in a Group of Danish Horses" (PDF). Journal of Equine Veterinary Science. 53: 68–73. doi:10.1016/j.jevs.2016.03.006. 16. ^ Menzies-Gow NJ, Harris PA, Elliott J (May 2017). "Prospective cohort study evaluating risk factors for the development of pasture-associated laminitis in the United Kingdom" (PDF). Equine Veterinary Journal. 49 (3): 300–306. doi:10.1111/evj.12606. PMID 27363591. 17. ^ Anderson M. "The Obel Grading System for Describing Laminitis". www.thehorse.com. The Horse. Archived from the original on 15 August 2014. Retrieved 30 July 2014. 18. ^ a b Ramey P, Bowker RM (2011). Care and Rehabilitation of the Equine Foot. Hoof Rehabilitation Publisher. pp. 234–253. ISBN 978-0-615-52453-5. 19. ^ Wongaumnuaykul S, Siedler C, Schobesberger H, Stanek C (2006). "Doppler sonographic evaluation of the digital blood flow in horses with laminitis or septic pododermatitis". Veterinary Radiology & Ultrasound. 47 (2): 199–205. doi:10.1111/j.1740-8261.2006.00128.x. PMID 16553154. 20. ^ Harris P, Bailey SR, Elliott J, Longland A (July 2006). "Countermeasures for pasture-associated laminitis in ponies and horses". The Journal of Nutrition. 136 (7 Suppl): 2114S–2121S. doi:10.1093/jn/136.7.2114S. PMID 16772514. 21. ^ Colahan P, Merritt A, Moore J, Mayhew I (December 1998). Equine Medicine and Surgery (Fifth ed.). Mosby. p. 408. ISBN 978-0-8151-1743-8. 22. ^ Pollitt C (November 2003). "Equine Laminitis" (PDF). Proceedings of the AAEP. 49. Archived (PDF) from the original on 2008-03-08. Retrieved 2008-04-19. 23. ^ Shulman L. "Making of a Miracle" (PDF). vet.osu.edu (reprint from The Blood-Horse). Archived (PDF) from the original on 17 December 2016. Retrieved 20 March 2017. 24. ^ MacAllister CG, Morgan SJ, Borne AT, Pollet RA (January 1993). "Comparison of adverse effects of phenylbutazone, flunixin meglumine, and ketoprofen in horses". Journal of the American Veterinary Medical Association. 202 (1): 71–7. PMID 8420909. 25. ^ Sabaté D, Homedes J, Mayós I, Calonge R, et al. (January 2005). Suxibuzone as a Therapeutical Alternative to Phenylbutazone in the Treatment of Lameness in Horses (PDF). 11th SIVE Congress. Pisa. Archived (PDF) from the original on 2005-05-29. Retrieved 2008-04-19. 26. ^ Doucet MY, Bertone AL, Hendrickson D, Hughes F, Macallister C, McClure S, et al. (January 2008). "Comparison of efficacy and safety of paste formulations of firocoxib and phenylbutazone in horses with naturally occurring osteoarthritis". Journal of the American Veterinary Medical Association. 232 (1): 91–7. doi:10.2460/javma.232.1.91. PMID 18167116. 27. ^ Pollitt CC (2003). "Medical Therapy of Laminitis". In Ross MW, Dyson SJ (eds.). Diagnosis and Management of Lameness in the Horse. St. Louis, MO: Saunders. p. 330. ISBN 0-7216-8342-8. 28. ^ Adair HS, Schmidhammer JL, Goble DO, et al. (1997). "Effects of acepromazine maleate, isoxsuprine hydrochloride and prazosin hydrochloride on laminar blood flow in healthy horses". Journal of Equine Veterinary Science. 17: 599–603. doi:10.1016/S0737-0806(97)80186-4. 29. ^ Belknap JK, Black SJ (2005). "Review of the Pathophysiology of the Developmental Stages of Equine Laminitis". Proceedings American Association of Equine Practitioners. 51. 30. ^ Eustace RA (1996). Explaining Laminitis and its Prevention. Cherokee, Ala.: Life Data Labs. pp. 29–31. ISBN 978-0-9518974-0-9. 31. ^ Eastman TG, Honnas CM, Hague BA, Moyer W, von der Rosen HD (February 1999). "Deep digital flexor tenotomy as a treatment for chronic laminitis in horses: 35 cases (1988-1997)" (PDF). Journal of the American Veterinary Medical Association. 214 (4): 517–9. PMID 10029854. 32. ^ Carter DW, Renfroe JB (July 2009). "A novel approach to the treatment and prevention of laminitis: botulinum toxin type A for the treatment of laminitis". Journal of Equine Veterinary Science. 29 (7): 595–600. doi:10.1016/j.jevs.2009.05.008. ## Further reading[edit] * Baxter GM, ed. (March 2011). Adams and Stashak's Lameness in Horses (6th ed.). Wiley-Blackwell. ISBN 978-0-813-81549-7. * Rooney JR (1998). The Lame Horse. Russell Meerdink Company. ISBN 978-0-929346-55-7. * Wagoner DM, ed. (1977). The Illustrated Veterinary Encyclopedia for Horsemen. Equine Research Inc. ISBN 978-0-935842-03-6. * Adams HR, Chalkley LW, Buchanan TM, Wagoner DM, eds. (1977). Veterinary Medications and Treatments for Horsemen. Equine Research Inc. ISBN 978-0-935842-01-2. * Giffin JM, Gore T (July 2008). Horse Owner's Veterinary Handbook (Third ed.). Howell Book House. ISBN 978-0-470-12679-0. * Jackson J (March 2001). Founder: Prevention & Cure the Natural Way. Star Ridge Company. ISBN 978-0-9658007-3-0. * Strasser H (2003). Who's Afraid of Founder. Laminitis Demystified: Causes, Prevention and Holistic Rehabilitation. Sabine Kells. ISBN 978-0-9685988-4-9. * Curtis S (June 2006). Corrective Farriery, a textbook of remedial horseshoeing. R & W Publications (Newmarket) Ltd. ISBN 978-1-899772-13-1. * Butler D (2004). The Principles of Horseshoeing II and The Principles of Horseshoeing III. ISBN 978-0-916992-26-2. * Riegel RJ, Hakola SE (1999). Illustrated Atlas of Clinical Equine Anatomy and Common Disorders of the Horse. One. Equistar Publications. ASIN B000Z4DW38. * Redden RF (Apr 15, 2004). "Understanding Laminitis". The Horse. * Jackson J (2001). Founder: Prevention & Cure the Natural Way. Star Ridge Publishing. ISBN 978-0-9658007-3-0. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Laminitis	c1299888	28,502	wikipedia	https://en.wikipedia.org/wiki/Laminitis	2021-01-18T19:09:41	{"wikidata": ["Q1339973"]}
Cardiofaciocutaneous syndrome is a disorder that affects many parts of the body, particularly the heart (cardio-), facial features (facio-), and the skin and hair (cutaneous). People with this condition also have delayed development and intellectual disability, usually ranging from moderate to severe. Heart defects occur in most people with cardiofaciocutaneous syndrome. The heart problems most commonly associated with this condition include malformations of one of the heart valves that impairs blood flow from the heart to the lungs (pulmonic stenosis), a hole between the two upper chambers of the heart (atrial septal defect), and a form of heart disease that enlarges and weakens the heart muscle (hypertrophic cardiomyopathy). Cardiofaciocutaneous syndrome is also characterized by distinctive facial features. These include a high forehead that narrows at the temples, a short nose, widely spaced eyes (ocular hypertelorism), outside corners of the eyes that point downward (down-slanting palpebral fissures), droopy eyelids (ptosis), a small chin, and low-set ears. Overall, the face is broad and long, and the facial features are sometimes described as "coarse." Skin abnormalities occur in almost everyone with cardiofaciocutaneous syndrome. Many affected people have dry, rough skin; dark-colored moles (nevi); wrinkled palms and soles; and a skin condition called keratosis pilaris, which causes small bumps to form on the arms, legs, and face. People with cardiofaciocutaneous syndrome also tend to have thin, dry, curly hair and sparse or absent eyelashes and eyebrows. Infants with cardiofaciocutaneous syndrome typically have weak muscle tone (hypotonia), feeding difficulties, and a failure to grow and gain weight at the normal rate (failure to thrive). Additional features of this disorder in children and adults can include an unusually large head (macrocephaly), short stature, problems with vision, and seizures. The signs and symptoms of cardiofaciocutaneous syndrome overlap significantly with those of two other genetic conditions, Costello syndrome and Noonan syndrome. The three conditions are distinguished by their genetic cause and specific patterns of signs and symptoms; however, it can be difficult to tell these conditions apart, particularly in infancy. Unlike Costello syndrome, which significantly increases a person's cancer risk, cancer does not appear to be a major feature of cardiofaciocutaneous syndrome. ## Frequency Cardiofaciocutaneous syndrome is a very rare condition whose incidence is unknown. Researchers estimate that 200 to 300 people worldwide have this condition. ## Causes Cardiofaciocutaneous syndrome can be caused by mutations in several genes. Mutations in the BRAF gene are most common, accounting for 75 to 80 percent of all cases. Another 10 to 15 percent of cases result from mutations in one of two similar genes, MAP2K1 and MAP2K2. Fewer than 5 percent of cases are caused by mutations in the KRAS gene. The BRAF, MAP2K1, MAP2K2, and KRAS genes provide instructions for making proteins that work together to transmit chemical signals from outside the cell to the cell's nucleus. This chemical signaling pathway, known as the RAS/MAPK pathway, is essential for normal development before birth. It helps control the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), cell movement, and the self-destruction of cells (apoptosis). Mutations in any of these genes can result in the characteristic features of cardiofaciocutaneous syndrome. The protein made from the mutated gene is overactive, which alters tightly regulated chemical signaling during development. The altered signaling interferes with the development of many organs and tissues, leading to the signs and symptoms of cardiofaciocutaneous syndrome. Some people with the signs and symptoms of cardiofaciocutaneous syndrome do not have an identified mutation in the BRAF, MAP2K1, MAP2K2, or KRAS gene. In these cases, affected individuals may actually have Costello syndrome or Noonan syndrome, which are also caused by mutations in genes involved in RAS/MAPK signaling. The proteins produced from these genes are all part of the same chemical signaling pathway, which helps explain why mutations in different genes can cause conditions with such similar signs and symptoms. The group of related conditions that includes cardiofaciocutaneous syndrome, Costello syndrome, and Noonan syndrome is often called the RASopathies. ### Learn more about the genes associated with Cardiofaciocutaneous syndrome * BRAF * KRAS * MAP2K1 * MAP2K2 ## Inheritance Pattern Cardiofaciocutaneous syndrome is considered to be an autosomal dominant condition, which means one copy of an altered gene in each cell is sufficient to cause the disorder. Cardiofaciocutaneous syndrome usually results from new gene mutations and occurs in people with no history of the disorder in their family. In a few reported cases, an affected person has inherited the condition from an affected parent. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Cardiofaciocutaneous syndrome	c1275081	28,503	medlineplus	https://medlineplus.gov/genetics/condition/cardiofaciocutaneous-syndrome/	2021-01-27T08:25:10	{"gard": ["9146"], "mesh": ["C535579"], "omim": ["115150"], "synonyms": []}
Distal trisomy 4q is a rare chromosomal anomaly syndrome, resulting from the partial duplication of the long arm of chromosome 4, with highly variable phenotype typically characterized by psychomotor delay, intellectual disability, craniofacial dysmorphism (microcephaly, low-set, prominent ears, downslanting palpebral fissures, hypertelorism, epicanthic folds, broad, prominent nasal bridge, high arched and cleft palate, micro-/retrognathia), seizures, as well as tooth and digital anomalies (clinodactyly, polydactyly). Cardiac malformations, renal anomalies, cryptorchidism, hypotonia and hearing impairment have also been reported. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Distal trisomy 4q	c4706362	28,504	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=96096	2021-01-23T18:15:18	{"icd-10": ["Q92.3"], "synonyms": ["Distal duplication 4q", "Telomeric duplication 4q", "Trisomy 4qter"]}
Resistance to thyrotropin-releasing hormone (TRH) syndrome is a type of central congenital hypothyroidism (see this term) characterized by low levels of thyroid hormones due to insufficient release of thyroid-stimulating hormone (TSH) caused by pituitary resistance to TRH. It may or may not be observed from birth. ## Epidemiology Prevalence is unknown. ## Clinical description The clinical manifestations are often subtle, probably as a result of trans-placental passage of some maternal thyroid hormone or due to the fact that many infants have some thyroid production of their own. More specific symptoms and signs often do not develop until several months of age. Common clinical features and signs include decreased activity and increased sleep, feeding difficulty and constipation, prolonged jaundice, myxedematous facies, large fontanels (especially posterior), macroglossia, a distended abdomen with umbilical hernia, and hypotonia. Goiter is always absent. Slow linear growth and developmental delay are usually apparent by 4-6 months of age. ## Etiology Resistance to TRH is caused by mutations in the TRH receptor gene (TRHR; 8q23). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Resistance to thyrotropin-releasing hormone syndrome	c4511136	28,505	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99832	2021-01-23T18:26:50	{"omim": ["618573"], "icd-10": ["E03.1"], "synonyms": ["Central hypothyroidism due to TRH receptor deficiency", "TRH resistance syndrome"]}
A number sign (#) is used with this entry because of evidence that progressive congenital myopathy with scoliosis (MYOSCO) is caused by homozygous mutation in the PAX7 gene (167410) on chromosome 1p36. Description Progressive congenital myopathy with scoliosis (MYOSCO) is an autosomal recessive skeletal muscle disorder characterized by infantile-onset of progressive muscle weakness and atrophy associated with scoliosis, variably impaired walking, and dysmorphic facial features (summary by Feichtinger et al., 2019). Clinical Features Feichtinger et al. (2019) reported 5 patients from 4 unrelated consanguineous families with MYOSCO. The families were from various geographic regions, including Canada, Germany, Palestine, and Saudi Arabia. The patients presented with axial or generalized hypotonia associated with skeletal muscle atrophy in the first days or months of life. All developed moderate to severe scoliosis. Walking ability was variable: 4 were able to walk after some delay and tended to show an abnormal gait, although 1 patient had a normal gait; 2 had areflexia. The most severely affected individual (patient 1, of Canadian descent) was wheelchair-bound and later bedridden by age 14 years. Variable dysmorphic features observed in the patients included ptosis, hypotonic facies, triangular face, flat nose, and low-set or posteriorly rotated ears. The most severely affected patient was the only one with swallowing difficulties requiring tube feeding, congenital contractures, a bell-shaped thorax, and respiratory insufficiency due to muscle weakness. He also had some additional abnormalities not observed in the other patients, including renal atrophy, hydronephrosis, hearing loss, nystagmus, and cryptorchidism. Patient 3, of Palestinian descent, died at 7 years of age and had 3 deceased sibs who were reportedly similarly affected. All patients had normal cognitive development, socialization, and behavior, and none had cardiac involvement, although the skeletal muscle disorder was progressive. Laboratory studies showed normal serum creatine kinase levels and EMG was normal or uninformative, excluding a neurogenic origin. Skeletal muscle biopsy of 3 patients showed mild variability in fiber size and shape of muscle fibers without diagnostic findings on routine staining. Later repeat biopsy of 1 patient showed more specific abnormalities, including focal endomysial fibrosis, angulated atrophic fibers, and fatty replacement. Obvious dystrophic features were not observed. Inheritance The transmission pattern of MYOSCO in the family reported by Feichtinger et al. (2019) was consistent with autosomal recessive inheritance. Molecular Genetics In 5 patients from 4 unrelated consanguineous families with MYOSCO, Feichtinger et al. (2019) identified homozygous mutations in the PAX7 gene (167410.0001-167410.0004). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing through different research centers, segregated with the disorder in all families. There were 2 nonsense mutations, a spice site mutation, and a missense mutation. Detailed RT-PCR and immunostaining studies on skeletal muscle biopsies from 2 patients showed severely reduced or complete absence of PAX7 and MYF5 (159990) expression, as well as other findings suggesting loss of myogenic satellite cells. The authors suggested a myopathic process that specifically affects muscle stem cells, causing exhaustion of the satellite cell pool that ultimately results in reduced skeletal muscle growth and regeneration. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	MYOPATHY, CONGENITAL, PROGRESSIVE, WITH SCOLIOSIS	None	28,506	omim	https://www.omim.org/entry/618578	2019-09-22T15:41:22	{"omim": ["618578"]}
Macrophage activation syndrome Other namesMAS SpecialtyRheumatology Macrophage-activation syndrome is a severe, potentially life-threatening, complication of several chronic rheumatic diseases of childhood. It occurs most commonly with systemic-onset juvenile idiopathic arthritis (SoJIA). In addition, MAS has been described in association with systemic lupus erythematosus (SLE), Kawasaki disease, and adult-onset Still's disease. It is thought to be closely related and pathophysiologically very similar to reactive (secondary) hemophagocytic lymphohistiocytosis (HLH).[1] The incidence of MAS is unknown as there is a wide spectrum of clinical manifestations, and episodes may remain unrecognized. ## Contents * 1 Signs and symptoms * 2 Cause * 3 Diagnosis * 4 Treatment * 5 References * 6 See also * 7 External links ## Signs and symptoms[edit] The hallmark clinical and laboratory features include high fever, hepatosplenomegaly, lymphadenopathy, pancytopenia, liver dysfunction, disseminated intravascular coagulation, hypofibrinogenemia, hyperferritinemia, and hypertriglyceridemia. Despite marked systemic inflammation, the erythrocyte sedimentation rate (ESR) is paradoxically depressed, caused by low fibrinogen levels. The low ESR helps to distinguish the disorder from a flare of the underlying rheumatic disorder, in which case the ESR is usually elevated. A bone marrow biopsy or aspirate usually shows hemophagocytosis. ## Cause[edit] In many cases a trigger is identified, often a viral infection, or a medication.[2] There is uncontrolled activation and proliferation of macrophages, and T lymphocytes, with a marked increase in circulating cytokines, such as IFN-gamma, and GM-CSF. The underlying causative event is unclear, and is the subject of ongoing research. In many cases of MAS, a decreased natural killer cell (NK-cell) function is found. ## Diagnosis[edit] A febrile patient with known or suspected sJia must be considered for macrophage activation if: * Ferritin >684 ng/ml and any 2 of the following: * Hemoglobin <90g/L (in infants <4 weeks: <100g/L) * Platelets <100 x 109/L * Neutrophils <1.0 x 109/L * Fasting triglycerides ≥3.0 mmol/L (i.e., ≥ 265mg/dl) * Fibrinogen ≤1.5 g/L[3] In addition, other specific markers of macrophage activation (e.g. soluble CD163), and lymphocyte activation (e.g. soluble IL-2 receptor) can be helpful. NK cell function analysis may show depressed NK function, or, flow cytometry may show a depressed NK cell population. [4] ## Treatment[edit] The best treatment for MAS has not been firmly established. Most commonly used treatments include high-dose glucocorticoids, and cyclosporine. In refractory cases treatment regimens are used similar to that in HLH. Anakinra may also be effective.[5] ## References[edit] 1. ^ Grom AA, Mellins ED (September 2010). "Macrophage activation syndrome: advances towards understanding pathogenesis". Curr Opin Rheumatol. 22 (5): 561–6. doi:10.1097/01.bor.0000381996.69261.71. PMC 4443835. PMID 20517154. 2. ^ Agarwal S (2011). "A rare trigger for macrophage activation syndrome". Rheumatology International. 31 (3): 405–7. doi:10.1007/s00296-009-1204-0. PMID 19834709. 3. ^ "Macrophage Activation Syndrome". 4. ^ Badugu, Srinivasarao (2010). "MACROPHAGE ACTIVATIONS SYNDROME, AN IMPORTANT DIFFERENTIAL DIAGNOSIS FOR SEPTIC SHOCK". Critical Care Medicine. 38. 5. ^ Canna, Scott W. (2012). "Making Sense of the Cytokine Storm". Pediatric Clinics of North America. 59 (2): 329–344. doi:10.1016/j.pcl.2012.03.002. PMC 3368378. PMID 22560573. ## See also[edit] * Cytokine release syndrome ## External links[edit] Classification D * MeSH: D055501 * SNOMED CT: 430478003 External resources * eMedicine: article/1380671 * Orphanet: 158061 * Macrophage Activation Syndrome, MedScape [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Macrophage activation syndrome	c1096155	28,507	wikipedia	https://en.wikipedia.org/wiki/Macrophage_activation_syndrome	2021-01-18T18:44:05	{"gard": ["12124"], "mesh": ["D055501"], "umls": ["C1096155"], "orphanet": ["158061"], "wikidata": ["Q6725504"]}
An autosomal dominant cerebellar ataxia type III that is characterized by the late-onset of ataxia, dysarthria and horizontal gaze nystagmus, and that is occasionally accompanied by pyramidal signs, tremor, decreased vibration sense and hearing difficulties. ## Epidemiology Spinocerebellar ataxia type 31 (SCA31) is the third most common form of ADCA in Japan, where more than 20 families have been reported to date. It is rarely found in other Asian countries and is extremely rare in Western countries. ## Clinical description The mean age of disease onset is 58 years but it can present between the ages of 8 to 83 years. Ataxia, dysarthria, and horizontal gaze nystagmus are the common manifestations of SCA31, and the disease duration can be more than 10 years. Less common manifestations include pyramidal signs, tremor, decreased vibration sense, hearing difficulties, and blepharospasm ## Etiology SCA31 is due to non-coding pentanucleotide repeat expansions in the BEAN1 gene (16q21), encoding protein BEAN1. ## Diagnostic methods Diagnosis is based on the characteristic clinical findings and molecular genetic testing. As the manifestations of SCA31 are not specific, diagnosis is only confirmed with the finding of a mutation in the BEAN1 gene ## Differential diagnosis Differential diagnosis includes other types of ADCA. ## Genetic counseling SCA31 is inherited autosomal dominantly with incomplete penetrance and genetic counseling is possible. Genetic counseling should be proposed to individuals having the disease-causing mutation informing them that there is 50% risk of passing the mutation to offspring. ## Management and treatment There is no cure for SCA31 and treatment is supportive. Physical therapy, as well as the use of canes and walkers, should be offered in order to maximize strength and maintain activity. Wheelchairs are eventually necessary. Speech therapy and communication devices may be useful to those with dysarthria. Dysphagia should be monitored to decrease the risk of aspiration pneumonia. In those with vertigo, vestibular suppressants may be beneficial. Annual neurological examinations are recommended to monitor disease progression. ## Prognosis Disease progression is very slow. Life expectancy is not reduced but the quality of life can be significantly affected. According to recent reports, patients can become wheelchair bound at age of 79 years, and died at age of 89 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Spinocerebellar ataxia type 31	c1861736	28,508	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=217012	2021-01-23T17:28:42	{"gard": ["9975"], "mesh": ["C566146"], "omim": ["117210"], "umls": ["C1861736"], "icd-10": ["G11.8"], "synonyms": ["SCA31"]}
A rare vascular anomaly characterized by absence of the hepatic segment of the inferior vena cava and presence of an enlarged azygos vein (or in rare cases hemiazygos vein, if there is a left-sided inferior vena cava) draining the venous blood from the caudal segments. The post-hepatic segment of the inferior vena cava is present, draining only the hepatic veins into the right atrium. Most patients remain asymptomatic, if the anomaly is isolated. Association with congenital heart disease and asplenia or polysplenia syndromes has been reported. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Azygos continuation of the inferior vena cava	c1859772	28,509	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99121	2021-01-23T17:45:51	{"icd-10": ["Q26.8"], "synonyms": ["Azygos continuation of the IVC", "Azygos continuation of the inferior caval vein", "Inferior vena cava interruption with azygos continuation"]}
This article needs attention from an expert in medicine. Please add a reason or a talk parameter to this template to explain the issue with the article. WikiProject Medicine may be able to help recruit an expert. (February 2009) Evans syndrome SpecialtyHematology Evans syndrome is an autoimmune disease in which an individual's immune system attacks their own red blood cells and platelets, the syndrome can include immune neutropenia.[1][2] These immune cytopenias may occur simultaneously or sequentially.[1][3] Its overall phenotype resembles a combination of autoimmune hemolytic anemia and immune thrombocytopenic purpura.[1][4][5] Autoimmune hemolytic anemia is a condition in which the red blood cells that normally carry oxygen and carbon dioxide are destroyed by an autoimmune process. Immune thrombocytopenic purpura is a condition in which platelets are destroyed by an autoimmune process. Platelets are a component of blood that contribute to the formation of blood clots in the body to prevent bleeding. The syndrome was first described in 1951 by R. S. Evans and colleagues.[1] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 4 Treatment * 5 Prognosis * 6 Epidemiology * 7 See also * 8 References * 9 External links ## Signs and symptoms[edit] The symptoms of Evans syndrome vary between patients depending on which blood cells are affected. If red blood cells are attacked, symptoms may include weakness and fatigue, paleness or jaundice, shortness of breath, lightheadedness, and/or a fast heartbeat. If platelets are attacked, symptoms may include increased bruising, prolonged nosebleeds, increased bleeding from minor cuts, and/or Petechiae. In the less common instance that white blood cells are attacked, symptoms may include increased proneness to infection, fevers, and/or mouth sores.[6][7] It has been variously reported that between 7.8%[4] and 23%[8] of patients who have autoimmune hemolytic anemia, will also have thrombocytopenia and thus Evans syndrome. The two cytopenias may occur together or sequentially.[1][3][9] ## Causes[edit] Although Evans syndrome seems to be a disorder of immune regulation, the exact pathophysiology is unknown, but a gradual loss of self-tolerance is postulated.[5] Autoantibodies targeted at different antigenic determinants on red cells and platelets are assumed to cause isolated episodes of hemolytic anemia and thrombocytopenia, respectively.[10] ## Diagnosis[edit] The diagnosis of primary Evans syndrome is made upon blood tests to confirm not only hemolytic anemia and immune thrombocytopenic purpura, but also a positive direct antiglobulin test (DAT) and an absence of any known underlying cause.[3] In 27% to 50% of cases there is an associated malignancy or a predisposing autoimmune disease (e.g. systemic lupus erythematosus), it is then common to denote it as secondary Evans syndrome.[4][5][11] Other antibodies may occur directed against neutrophils and lymphocytes,[12] and "immunopancytopenia" has been suggested as a term for this syndrome.[13] ## Treatment[edit] Initial treatment is with glucocorticoid corticosteroids or intravenous immunoglobulin, a treatment that is also used in ITP cases.[5][14][15] In children, it can remain well controlled with a long term immunosuppressant therapy that will occasionally lead to a spontaneous complete resolution of the condition.[16] Although the majority of cases initially respond well to treatment, relapses are not uncommon[3][5] and immunosuppressive drugs[3][5] (e.g. ciclosporin,[17][18] mycophenolate mofetil, vincristine[19] and danazol[20]) are subsequently used,[3] or combinations of these.[21] The off-label use of rituximab (trade name Rituxan) has produced some good results in acute and refractory cases,[3][5][22][23] although further relapse may occur within a year.[3] Splenectomy is effective in some cases,[24] but relapses are not uncommon.[25] The only prospect for a permanent cure is the high-risk option of an allogeneic hematopoietic stem cell transplantation (SCT).[26][27] ## Prognosis[edit] In a nationwide study of Evans syndrome the median survival was 7.2 years (primary Evans syndrome: 10.9 years; secondary Evans syndrome: 1.7 years). Secondary Evans syndrome was associated with higher mortality rate than primary Evans syndrome, with a 5-year survival of 38%. Among patients with Evans syndrome, the prevailing causes of death were bleeding, infections, and hematological cancer.[4] It has been observed that there is a risk of developing other autoimmune problems and hypogammaglobulinemia,[28] in one cohort 58% of children with Evans syndrome had CD4-/CD8- T cells which is a strong predictor for having autoimmune lymphoproliferative syndrome.[29] ## Epidemiology[edit] Evans syndrome is considered a very rare autoimmune disease. Only one study has estimated incidence and prevalence adults. In Denmark in 2016 the annual incidence was 1.8 per 1,000,000 person years, and the prevalence was 21.3 per 1,000,000 living persons.[4] In pre-pubertal children the incidence has been estimated to be between 0.7 to 1.2 per 1,000,000 person-years.[30][31] ## See also[edit] * Hematology ## References[edit] 1. ^ a b c d e Evans RS, Takahashi K, Duane RT, Payne R, Liu C (1951). "Primary thrombocytopenic purpura and acquired hemolytic anemia; evidence for a common etiology". Archives of Internal Medicine. 87 (1): 48–65. doi:10.1001/archinte.1951.03810010058005. PMID 14782741. 2. ^ "Evans syndrome". Genetic and Rare Diseases Information Center. Retrieved 2018-04-17. 3. ^ a b c d e f g h Norton A, Roberts I (2006). "Management of Evans syndrome". Br. J. Haematol. 132 (2): 125–37. doi:10.1111/j.1365-2141.2005.05809.x. PMID 16398647. S2CID 7633446. 4. ^ a b c d e Hansen DL; Möller S; Andersen K; Gaist D; Frederiksen H (2019). "Evans syndrome in adults - incidence, prevalence, and survival in a nationwide cohort". Am J Hematol. 94 (10): 1081–1090. doi:10.1002/ajh.25574. PMID 31292991. S2CID 195879785. 5. ^ a b c d e f g Michel M; Chanet V; Dechartres A; Morin A-S; Piette J-C; Cirasino L; Emilia G; Zaja F; Ruggeri M; Andrès E; Bierling P; Godeau B; Rodeghiero F (2009). "The spectrum of Evans syndrome in adults: new insight into the disease based on the analysis of 68 cases". Blood. 114 (15): 3167–3172. doi:10.1182/blood-2009-04-215368. PMID 19638626. 6. ^ "Evans syndrome \| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2020-11-27. 7. ^ "Evans Syndrome \| Symptoms & Causes \| Boston Children's Hospital". www.childrenshospital.org. Retrieved 2020-11-27. 8. ^ Cai JR, Yu QZ, Zhang FQ (1989). "[Autoimmune hemolytic anemia: clinical analysis of 100 cases]". Zhonghua Nei Ke Za Zhi (in Chinese). 28 (11): 670–3, 701–2. PMID 2632179. 9. ^ Ng SC (1992). "Evans syndrome: a report on 12 patients". Clinical and Laboratory Haematology. 14 (3): 189–93. doi:10.1111/j.1365-2257.1992.tb00364.x. PMID 1451398. 10. ^ "EVANS SYNDROME". 2019-10-22. Cite journal requires `\|journal=` (help) 11. ^ "Evans syndrome". Genetic and Rare Diseases Information Center. Retrieved 2019-07-28. 12. ^ Pegels JG, Helmerhorst FM, van Leeuwen EF, van de Plas-van Dalen C, Engelfriet CP, von dem Borne AE (1982). "The Evans syndrome: characterization of the responsible autoantibodies". Br. J. Haematol. 51 (3): 445–50. doi:10.1111/j.1365-2141.1982.tb02801.x. PMID 7104228. 13. ^ Pui CH, Wilimas J, Wang W (1980). "Evans syndrome in childhood". J. Pediatr. 97 (5): 754–8. doi:10.1016/S0022-3476(80)80258-7. PMID 7191890. 14. ^ Nuss R, Wang W (1987). "Intravenous gamma globulin for thrombocytopenia in children with Evans syndrome". The American Journal of Pediatric Hematology/Oncology. 9 (2): 164–7. doi:10.1097/00043426-198722000-00012. PMID 2438958. S2CID 19749102. 15. ^ Mehta JB, Singhal SB, Mehta BC (1992). "Intravenous immunoglobulin therapy of idiopathic thrombocytopenia". The Journal of the Association of Physicians of India. 40 (5): 340–2. PMID 1483999. 16. ^ "Evan's Syndrome". Boston Children's Hospital. Retrieved 2020-11-23. 17. ^ Emilia G, Messora C, Longo G, Bertesi M (1996). "Long-term salvage treatment by cyclosporin in refractory autoimmune haematological disorders". Br. J. Haematol. 93 (2): 341–4. doi:10.1046/j.1365-2141.1996.4871026.x. PMID 8639426. S2CID 11724766. 18. ^ Liu H, Shao Z, Jing L (2001). "[The effectiveness of cyclosporin A in the treatment of autoimmune hemolytic anemia and Evans syndrome]". Zhonghua Xue Ye Xue Za Zhi (in Chinese). 22 (11): 581–3. PMID 11855146. 19. ^ Yokoyama K; Kojima M; Komatsumoto S; et al. (1992). "[Thrombotic thrombocytopenic purpura achieving complete remission by slow infusion of vincristine]". Rinsho Ketsueki (in Japanese). 33 (8): 1084–9. PMID 1404865. 20. ^ Koike M; Ishiyama T; Saito K; et al. (1993). "[Effective danazol therapy for a patient with Evans syndrome]". Rinsho Ketsueki (in Japanese). 34 (2): 143–6. PMID 8492411. 21. ^ Scaradavou A, Bussel J (1995). "Evans syndrome. Results of a pilot study utilizing a multiagent treatment protocol". J. Pediatr. Hematol. Oncol. 17 (4): 290–5. doi:10.1097/00043426-199511000-00003. PMID 7583383. S2CID 20968070. 22. ^ Zecca M; Nobili B; Ramenghi U; et al. (15 May 2003). "Rituximab for the treatment of refractory autoimmune hemolytic anemia in children". Blood. 101 (10): 3857–61. doi:10.1182/blood-2002-11-3547. PMID 12531800. 23. ^ Shanafelt TD, Madueme HL, Wolf RC, Tefferi A (November 2003). "Rituximab for immune cytopenia in adults: idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, and Evans syndrome" (PDF). Mayo Clin. Proc. 78 (11): 1340–6. doi:10.4065/78.11.1340. PMID 14601692. Archived from the original (PDF) on 2006-03-13. Retrieved 2007-04-18. 24. ^ Hamidah A, Thambidorai CR, Jamal R (2005). "Prolonged remission after splenectomy for refractory Evans syndrome--a case report and literature review". Southeast Asian J. Trop. Med. Public Health. 36 (3): 762–4. PMID 16124452. 25. ^ Mathew P, Chen G, Wang W (1997). "Evans syndrome: results of a national survey". J. Pediatr. Hematol. Oncol. 19 (5): 433–7. doi:10.1097/00043426-199709000-00005. PMID 9329465. S2CID 24014798. 26. ^ Martino R, Sureda A, Brunet S (1997). "Peripheral blood stem cell mobilization in refractory autoimmune Evans syndrome: a cautionary case report". Bone Marrow Transplant. 20 (6): 521. doi:10.1038/sj.bmt.1700924. PMID 9313889. 27. ^ Oyama Y, Papadopoulos EB, Miranda M, Traynor AE, Burt RK (2001). "Allogeneic stem cell transplantation for Evans syndrome". Bone Marrow Transplant. 28 (9): 903–5. doi:10.1038/sj.bmt.1703237. PMID 11781654. 28. ^ Wang WC (1988). "Evans syndrome in childhood: pathophysiology, clinical course, and treatment". The American Journal of Pediatric Hematology/Oncology. 10 (4): 330–8. doi:10.1097/00043426-198824000-00013. PMID 3071168. S2CID 20125761. 29. ^ Teachey DT; Manno CS; Axsom KM; et al. (2005). "Unmasking Evans syndrome: T-cell phenotype and apoptotic response reveal autoimmune lymphoproliferative syndrome (ALPS)". Blood. 105 (6): 2443–8. doi:10.1182/blood-2004-09-3542. PMID 15542578. 30. ^ Mannering N; Hansen DL; Frederiksen H (2020). "Evans syndrome in children below 13 years of age - A nationwide population-based cohort study". PLOS ONE. 15 (4): e0231284. doi:10.1371/journal.pone.0231284. PMC 7145102. PMID 32271826. 31. ^ Aladjidi N; Fernandes H; Leblanc T; Vareliette A; Rieux-Laucat F; Bertrand Y; Chambost H; Pasquet M; Mazingue F; Guitton C; Pellier I; Roqueplan-Bellmann F; Armari-Alla C; Thomas C; Marie-Cardine A; Lejars O; Fouyssac F; Bayart S; Lutz P; Piguet C; Jeziorski E; Rohrlich P; Lemoine P; Bodet D; Paillard C; Couillault G; Millot F; Fischer A; Pérel Y; Leverger G (2015). "Evans Syndrome in Children: Long-Term Outcome in a Prospective French National Observational Cohort". Front Pediatr. 3 (79). doi:10.3389/fped.2015.00079. PMID 32271826. ## External links[edit] Classification D * ICD-10: D69.3 * ICD-9-CM: 287.32 * MeSH: C536380 C536380, C536380 * DiseasesDB: 29724 External resources * eMedicine: ped/721 * v * t * e Disorders of bleeding and clotting Coagulation · coagulopathy · Bleeding diathesis Clotting By cause * Clotting factors * Antithrombin III deficiency * Protein C deficiency * Activated protein C resistance * Protein S deficiency * Factor V Leiden * Prothrombin G20210A * Platelets * Sticky platelet syndrome * Thrombocytosis * Essential thrombocythemia * DIC * Purpura fulminans * Antiphospholipid syndrome Clots * Thrombophilia * Thrombus * Thrombosis * Virchow's triad * Trousseau sign of malignancy By site * Deep vein thrombosis * Bancroft's sign * Homans sign * Lisker's sign * Louvel's sign * Lowenberg's sign * Peabody's sign * Pratt's sign * Rose's sign * Pulmonary embolism * Renal vein thrombosis Bleeding By cause Thrombocytopenia * Thrombocytopenic purpura: ITP * Evans syndrome * TM * TTP * Upshaw–Schulman syndrome * Heparin-induced thrombocytopenia * May–Hegglin anomaly Platelet function * adhesion * Bernard–Soulier syndrome * aggregation * Glanzmann's thrombasthenia * platelet storage pool deficiency * Hermansky–Pudlak syndrome * Gray platelet syndrome Clotting factor * Hemophilia * A/VIII * B/IX * C/XI * von Willebrand disease * Hypoprothrombinemia/II * Factor VII deficiency * Factor X deficiency * Factor XII deficiency * Factor XIII deficiency * Dysfibrinogenemia * Congenital afibrinogenemia Signs and symptoms * Bleeding * Bruise * Hematoma * Petechia * Purpura * Nonthrombocytopenic purpura By site * head * Epistaxis * Hemoptysis * Intracranial hemorrhage * Hyphema * Subconjunctival hemorrhage * torso * Hemothorax * Hemopericardium * Pulmonary hematoma * abdomen * Gastrointestinal bleeding * Hemobilia * Hemoperitoneum * Hematocele * Hematosalpinx * joint * Hemarthrosis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Evans syndrome	c0272126	28,510	wikipedia	https://en.wikipedia.org/wiki/Evans_syndrome	2021-01-18T18:55:54	{"gard": ["6389"], "mesh": ["C536380"], "umls": ["C0272126"], "orphanet": ["1959"], "wikidata": ["Q3109873"]}
1\. Meiosis I 2\. Meiosis II 3\. Fertilization 4\. Zygote The left image at the blue arrow is nondisjunction taking place during meiosis II. The right image at the green arrow is nondisjunction taking place during meiosis I. Nondisjunction is when chromosomes fail to separate normally resulting in a gain or loss of chromosomes. Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate properly during cell division. There are three forms of nondisjunction: failure of a pair of homologous chromosomes to separate in meiosis I, failure of sister chromatids to separate during meiosis II, and failure of sister chromatids to separate during mitosis.[1][2][3] Nondisjunction results in daughter cells with abnormal chromosome numbers (aneuploidy). Calvin Bridges and Thomas Hunt Morgan are credited with discovering nondisjunction in Drosophila melanogaster sex chromosomes in the spring of 1910, while working in the Zoological Laboratory of Columbia University.[4] ## Contents * 1 Types * 1.1 Meiosis II * 1.2 Mitosis * 2 Molecular mechanisms * 2.1 Central role of the spindle assembly checkpoint * 2.2 Sex-specific differences in meiosis * 2.3 Age-related loss of cohesin ties * 3 Consequences * 3.1 Monosomy * 3.1.1 Turner syndrome (X monosomy) (45, X0) * 3.2 Autosomal trisomy * 3.2.1 Down syndrome (trisomy 21) * 3.2.2 Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13) * 3.3 Sex chromosome aneuploidy * 3.3.1 Klinefelter syndrome (47, XXY) * 3.3.2 XYY Male (47, XYY) * 3.3.3 Trisomy X (47,XXX) * 3.4 Uniparental disomy * 3.5 Mosaicism syndromes * 3.6 Mosaicism in malignant transformation * 4 Diagnosis * 4.1 Preimplantation genetic diagnosis * 4.2 Karyotyping * 4.3 Polar body diagnosis * 4.4 Blastomere biopsy * 5 Lifestyle/environmental hazards * 6 References ## Types[edit] In general, nondisjunction can occur in any form of cell division that involves ordered distribution of chromosomal material. Higher animals have three distinct forms of such cell divisions: Meiosis I and meiosis II are specialized forms of cell division occurring during generation of gametes (eggs and sperm) for sexual reproduction, mitosis is the form of cell division used by all other cells of the body. ### Meiosis II[edit] Ovulated eggs become arrested in metaphase II until fertilization triggers the second meiotic division.[5] Similar to the segregation events of mitosis, the pairs of sister chromatids resulting from the separation of bivalents in meiosis I are further separated in anaphase of meiosis II. In oocytes, one sister chromatid is segregated into the second polar body, while the other stays inside the egg. During spermatogenesis, each meiotic division is symmetric such that each primary spermatocyte gives rise to 2 secondary spermatocytes after meiosis I, and eventually 4 spermatids after meiosis II. Meiosis II-nondisjunction may also result in aneuploidy syndromes, but only to a much smaller extent than do segregation failures in meiosis I.[6] Nondisjunction of sister chromatids during mitosis: Left: Metaphase of mitosis. Chromosome line up in the middle plane, the mitotic spindle forms and the kinetochores of sister chromatids attach to the microtubules. Right: Anaphase of mitosis, where sister chromatids separate and the microtubules pull them in opposite directions. The chromosome shown in red fails to separate properly, its sister chromatids stick together and get pulled to the same side, resulting in mitotic nondisjunction of this chromosome. ### Mitosis[edit] Division of somatic cells through mitosis is preceded by replication of the genetic material in S phase. As a result, each chromosome consists of two sister chromatids held together at the centromere. In the anaphase of mitosis, sister chromatids separate and migrate to opposite cell poles before the cell divides. Nondisjunction during mitosis leads to one daughter receiving both sister chromatids of the affected chromosome while the other gets none.[2][3] This is known as a chromatin bridge or an anaphase bridge. Mitotic nondisjunction results in somatic mosaicism, since only daughter cells originating from the cell where the nondisjunction event has occurred will have an abnormal number of chromosomes.[3] Nondisjunction during mitosis can contribute to the development of some forms of cancer, e.g. retinoblastoma (see below).[7] Chromosome nondisjunction in mitosis can be attributed to the inactivation of topoisomerase II, condensin, or separase.[8] Meiotic nondisjunction has been well studied in Saccharomyces cerevisiae. This yeast undergoes mitosis similarly to other eukaryotes. Chromosome bridges occur when sister chromatids are held together post replication by DNA-DNA topological entanglement and the cohesion complex.[9] During anaphase, cohesin is cleaved by separase.[10] Topoisomerase II and condensin are responsible for removing catenations.[11] ## Molecular mechanisms[edit] ### Central role of the spindle assembly checkpoint[edit] The spindle assembly checkpoint (SAC) is a molecular safe-guarding mechanism that governs proper chromosome segregation in eukaryotic cells.[12] SAC inhibits progression into anaphase until all homologous chromosomes (bivalents, or tetrads) are properly aligned to the spindle apparatus. Only then, SAC releases its inhibition of the anaphase promoting complex (APC), which in turn irreversibly triggers progression through anaphase. ### Sex-specific differences in meiosis[edit] Surveys of cases of human aneuploidy syndromes have shown that most of them are maternally derived.[5] This raises the question: Why is female meiosis more error prone? The most obvious difference between female oogenesis and male spermatogenesis is the prolonged arrest of oocytes in late stages of prophase I for many years up to several decades. Male gametes on the other hand quickly go through all stages of meiosis I and II. Another important difference between male and female meiosis concerns the frequency of recombination between homologous chromosomes: In the male, almost all chromosome pairs are joined by at least one crossover, while more than 10% of human oocytes contain at least one bivalent without any crossover event. Failures of recombination or inappropriately located crossovers have been well documented as contributors to the occurrence of nondisjunction in humans.[5] ### Age-related loss of cohesin ties[edit] Due to the prolonged arrest of human oocytes, weakening of cohesive ties holding together chromosomes and reduced activity of the SAC may contribute to maternal age-related errors in segregation control.[6][13] The cohesin complex is responsible for keeping together sister chromatids and provides binding sites for spindle attachment. Cohesin is loaded onto newly replicated chromosomes in oogonia during fetal development. Mature oocytes have only limited capacity for reloading cohesin after completion of S phase. The prolonged arrest of human oocytes prior to completion of meiosis I may therefore result in considerable loss of cohesin over time. Loss of cohesin is assumed to contribute to incorrect microtubule-kinetochore attachment and chromosome segregation errors during meiotic divisions.[6] ## Consequences[edit] The result of this error is a cell with an imbalance of chromosomes. Such a cell is said to be aneuploid. Loss of a single chromosome (2n-1), in which the daughter cell(s) with the defect will have one chromosome missing from one of its pairs, is referred to as a monosomy. Gaining a single chromosome, in which the daughter cell(s) with the defect will have one chromosome in addition to its pairs is referred to as a trisomy.[3] In the event that an aneuploidic gamete is fertilized, a number of syndromes might result. ### Monosomy[edit] The only known survivable monosomy in humans is Turner syndrome, where the affected individual is monosomic for the X chromosome (see below). Other monosomies are usually lethal during early fetal development, and survival is only possible if not all the cells of the body are affected in case of a mosaicism (see below), or if the normal number of chromosomes is restored via duplication of the single monosomic chromosome ("chromosome rescue").[2] #### Turner syndrome (X monosomy) (45, X0)[edit] Karyotype of X monosomy (Turner syndrome) This condition is characterized by the presence of only one X chromosome and no Y chromosome (see bottom right corner). Complete loss of an entire X chromosome accounts for about half the cases of Turner syndrome. The importance of both X chromosomes during embryonic development is underscored by the observation that the overwhelming majority (>99%) of fetuses with only one X chromosome (karyotype 45, X0) are spontaneously aborted.[14] ### Autosomal trisomy[edit] The term autosomal trisomy means that a chromosome other than the sex chromosomes X and Y is present in 3 copies instead of the normal number of 2 in diploid cells. #### Down syndrome (trisomy 21)[edit] Karyotype of trisomy 21 (Down syndrome) Note that chromosome 21 is present in 3 copies, while all other chromosomes show the normal diploid state with 2 copies. Most cases of trisomy of chromosome 21 are caused by a nondisjunction event during meiosis I (see text). Down syndrome, a trisomy of chromosome 21, is the most common anomaly of chromosome number in humans.[2] The majority of cases result from nondisjunction during maternal meiosis I.[14] Trisomy occurs in at least 0.3% of newborns and in nearly 25% of spontaneous abortions. It is the leading cause of pregnancy wastage and is the most common known cause of mental retardation.[15] It is well documented that advanced maternal age is associated with greater risk of meiotic nondisjunction leading to Down syndrome. This may be associated with the prolonged meiotic arrest of human oocytes potentially lasting for more than four decades.[13] #### Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13)[edit] Human trisomies compatible with live birth, other than Down syndrome (trisomy 21), are Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13).[1][2] Complete trisomies of other chromosomes are usually not viable and represent a relatively frequent cause of miscarriage. Only in rare cases of a mosaicism, the presence of a normal cell line, in addition to the trisomic cell line, may support the development of a viable trisomy of the other chromosomes.[2] ### Sex chromosome aneuploidy[edit] The term sex chromosome aneuploidy summarizes conditions with an abnormal number of sex chromosomes, i.e. other than XX (female) or XY (male). Formally, X chromosome monosomy (Turner syndrome, see above) can also be classified as a form of sex chromosome aneuploidy. #### Klinefelter syndrome (47, XXY)[edit] Klinefelter syndrome is the most common sex chromosome aneuploidy in humans. It represents the most frequent cause of hypogonadism and infertility in men. Most cases are caused by nondisjunction errors in paternal meiosis I.[2] About eighty percent of individuals with this syndrome have one extra X chromosome resulting in the karyotype XXY. The remaining cases have either multiple additional sex chromosomes (48,XXXY; 48,XXYY; 49,XXXXY), mosaicism (46,XY/47,XXY), or structural chromosome abnormalities.[2] #### XYY Male (47, XYY)[edit] The incidence of XYY syndrome is approximately 1 in 800-1000 male births. Many cases remain undiagnosed because of their normal appearance and fertility, and the absence of severe symptoms. The extra Y chromosome is usually a result of nondisjunction during paternal meiosis II.[2] #### Trisomy X (47,XXX)[edit] Trisomy X is a form of sex chromosome aneuploidy where females have three instead of two X chromosomes. Most patients are only mildly affected by neuropsychological and physical symptoms. Studies examining the origin of the extra X chromosome observed that about 58-63% of cases were caused by nondisjunction in maternal meiosis I, 16-18% by nondisjunction in maternal meiosis II, and the remaining cases by post-zygotic, i.e. mitotic, nondisjunction.[16] ### Uniparental disomy[edit] Uniparental disomy denotes the situation where both chromosomes of a chromosome pair are inherited from the same parent and are therefore identical. This phenomenon most likely is the result of a pregnancy that started as a trisomy due to nondisjunction. Since most trisomies are lethal, the fetus only survives because it loses one of the three chromosomes and becomes disomic. Uniparental disomy of chromosome 15 is, for example, seen in some cases of Prader-Willi syndrome and Angelman syndrome.[14] ### Mosaicism syndromes[edit] Mosaicism syndromes can be caused by mitotic nondisjunction in early fetal development. As a consequence, the organism evolves as a mixture of cell lines with differing ploidy (number of chromosomes). Mosaicism may be present in some tissues, but not in others. Affected individuals may have a patchy or assymmetric appearance. Examples of mosaicism syndromes include Pallister-Killian syndrome and Hypomelanosis of Ito.[14] ### Mosaicism in malignant transformation[edit] Loss of a tumor suppressor gene locus according to the two-hit model: In the first hit, the tumor suppressor gene on one of the two chromosomes is affected by a mutation that makes the gene product non-functional. This mutation may arise spontaneously as a DNA replication error or may be induced by a DNA damaging agent. The second hit removes the remaining wild-type chromosome, for example through a mitotic nondisjunction event. There are several other potential mechanisms for each of the two steps, for example an additional mutation, an unbalanced translocation, or a gene deletion by recombination. As a result of the double lesion, the cell may become malignant because it is no longer able to express the tumor suppressor protein. Development of cancer often involves multiple alterations of the cellular genome (Knudson hypothesis). Human retinoblastoma is a well studied example of a cancer type where mitotic nondisjunction can contribute to malignant transformation: Mutations of the RB1 gene, which is located on chromosome 13 and encodes the tumor suppressor retinoblastoma protein, can be detected by cytogenetic analysis in many cases of retinoblastoma. Mutations of the RB1 locus in one copy of chromosome 13 are sometimes accompanied by loss of the other wild-type chromosome 13 through mitotic nondisjunction. By this combination of lesions, affected cells completely lose expression of functioning tumor suppressor protein.[7] ## Diagnosis[edit] ### Preimplantation genetic diagnosis[edit] Pre-implantation genetic diagnosis (PGD or PIGD) is a technique used to identify genetically normal embryos and is useful for couples who have a family history of genetic disorders. This is an option for people choosing to procreate through IVF. PGD is considered difficult due to it being both time consuming and having success rates only comparable to routine IVF.[17] ### Karyotyping[edit] Karyotyping involves performing an amniocentesis in order to study the cells of an unborn fetus during metaphase 1. Light microscopy can be used to visually determine if aneuploidy is an issue.[18] ### Polar body diagnosis[edit] Polar body diagnosis (PBD) can be used to detect maternally derived chromosomal aneuploidies as well as translocations in oocytes. The advantage of PBD over PGD is that it can be accomplished in a short amount of time. This is accomplished through zona drilling or laser drilling.[19] ### Blastomere biopsy[edit] Blastomere biopsy is a technique in which blastomeres are removed from the zona pellucida. It is commonly used to detect aneuploidy.[20] Genetic analysis is conducted once the procedure is complete. Additional studies are needed to assess the risk associated with the procedure.[21] ## Lifestyle/environmental hazards[edit] Exposure of spermatozoa to lifestyle, environmental and/or occupational hazards may increase the risk of aneuploidy. Cigarette smoke is a known aneugen (aneuploidy inducing agent). It is associated with increases in aneuploidy ranging from 1.5 to 3.0-fold.[22][23] Other studies indicate factors such as alcohol consumption,[24] occupational exposure to benzene,[25] and exposure to the insecticides fenvalerate[26] and carbaryl[27] also increase aneuploidy. ## References[edit] 1. ^ a b Simmons, D. Peter Snustad, Michael J. (2006). Principles of genetics (4th ed.). New York, NY [u.a.]: Wiley. ISBN 9780471699392. 2. ^ a b c d e f g h i Bacino, C.A.; Lee, B. (2011). "Chapter 76: Cytogenetics". In Kliegman, R.M.; Stanton, B.F.; St. Geme, J.W.; Schor, N.F.; Behrman, R.E. (eds.). Nelson Textbook of Pediatrics, 19th Edition (19th ed.). Philadelphia: Saunders. pp. 394–413. ISBN 9781437707557. 3. ^ a b c d Strachan, Tom; Read, Andrew (2011). Human molecular genetics (4th ed.). New York: Garland Science. ISBN 9780815341499. 4. ^ Thomas Hunt Morgan (August 31, 2012). Sex-Linked Inheritance in Drosophila. Ulan Press. pp. 10–11. 5. ^ a b c Nagaoka, SI; Hassold, TJ; Hunt, PA (Jun 18, 2012). "Human aneuploidy: mechanisms and new insights into an age-old problem". Nature Reviews Genetics. 13 (7): 493–504. doi:10.1038/nrg3245. PMC 3551553. PMID 22705668. 6. ^ a b c Jones, K. T.; Lane, S. I. R. (27 August 2013). "Molecular causes of aneuploidy in mammalian eggs". Development. 140 (18): 3719–3730. doi:10.1242/dev.090589. PMID 23981655. 7. ^ a b eds, Charles R. Scriver ... []; et al. (2005). The online metabolic & molecular bases of inherited disease (8th ed.). New York: McGraw-Hill. ISBN 9780079130358. 8. ^ Quevedo, O; García-Luis, J; Matos-Perdomo, E; Aragón, L; Machín, F (2012). "Nondisjunction of a single chromosome leads to breakage and activation of DNA damage checkpoint in G2". PLOS Genetics. 8 (2): e1002509. doi:10.1371/journal.pgen.1002509. PMC 3280967. PMID 22363215. 9. ^ Vaahtokari, A; Aberg, T; Thesleff, I (Jan 1996). "Apoptosis in the developing tooth: association with an embryonic signaling center and suppression by EGF and FGF-4". Development. 122 (1): 121–9. PMID 8565823. 10. ^ Banks, P (Feb 1977). "Pulp changes after anterior mandibular subapical osteotomy in a primate model". Journal of Maxillofacial Surgery. 5 (1): 39–48. doi:10.1016/s0301-0503(77)80074-x. PMID 0403247. 11. ^ Holm, C; Goto, T; Wang, JC; Botstein, D (Jun 1985). "DNA topoisomerase II is required at the time of mitosis in yeast". Cell. 41 (2): 553–63. doi:10.1016/s0092-8674(85)80028-3. PMID 2985283. 12. ^ Sun, S.-C.; Kim, N.-H. (14 November 2011). "Spindle assembly checkpoint and its regulators in meiosis". Human Reproduction Update. 18 (1): 60–72. doi:10.1093/humupd/dmr044. PMID 22086113. 13. ^ a b Eichenlaub-Ritter, Ursula (2012). "Oocyte ageing and its cellular basis". The International Journal of Developmental Biology. 56 (10–11–12): 841–852. doi:10.1387/ijdb.120141ue. PMID 23417406. 14. ^ a b c d Gleason, H. William; Taeusch, Roberta A.; Ballard, Christine A., eds. (2005). Avery's diseases of the newborn (8th ed.). Philadelphia, Pa.: W.B. Saunders. ISBN 978-0721693477. 15. ^ Koehler, KE; Hawley, RS; Sherman, S; Hassold, T (1996). "Recombination and nondisjunction in humans and flies". Human Molecular Genetics. 5 Spec No: 1495–504. doi:10.1093/hmg/5.Supplement_1.1495. PMID 8875256. 16. ^ Tartaglia, NR; Howell, S; Sutherland, A; Wilson, R; Wilson, L (May 11, 2010). "A review of trisomy X (47,XXX)". Orphanet Journal of Rare Diseases. 5: 8. doi:10.1186/1750-1172-5-8. PMC 2883963. PMID 20459843. 17. ^ Harper, JC; Harton G (2010). "The use of arrays in preimplantation genetic diagnosis and screening". Fertil Steril. 94 (4): 1173–1177. doi:10.1016/j.fertnstert.2010.04.064. PMID 20579641. 18. ^ "Karyotyping". National Institute of Health. Retrieved 7 May 2014. 19. ^ Montag, M; van der Ven, K; Rösing, B; van der Ven, H (2009). "Polar body biopsy: a viable alternative to preimplantation genetic diagnosis and screening". Reproductive Biomedicine Online. 18 Suppl 1: 6–11. doi:10.1016/s1472-6483(10)60109-5. PMID 19281658. 20. ^ Parnes, YM (Mar–Apr 1989). "RCT controversy". Journal of Obstetric, Gynecologic, & Neonatal Nursing. 18 (2): 90. doi:10.1111/j.1552-6909.1989.tb00470.x. PMID 2709181. 21. ^ Yu, Y; Zhao, Y; Li, R; Li, L; Zhao, H; Li, M; Sha, J; Zhou, Q; Qiao, J (Dec 6, 2013). "Assessment of the risk of blastomere biopsy during preimplantation genetic diagnosis in a mouse model: reducing female ovary function with an increase in age by proteomics method". Journal of Proteome Research. 12 (12): 5475–86. doi:10.1021/pr400366j. PMID 24156634. 22. ^ Shi Q, Ko E, Barclay L, Hoang T, Rademaker A, Martin R (2001). "Cigarette smoking and aneuploidy in human sperm". Mol. Reprod. Dev. 59 (4): 417–21. doi:10.1002/mrd.1048. PMID 11468778. 23. ^ Rubes J, Lowe X, Moore D, Perreault S, Slott V, Evenson D, Selevan SG, Wyrobek AJ (1998). "Smoking cigarettes is associated with increased sperm disomy in teenage men". Fertil. Steril. 70 (4): 715–23. doi:10.1016/S0015-0282(98)00261-1. PMID 9797104. 24. ^ Benassi-Evans B, Fenech M (2011). "Chronic alcohol exposure induces genome damage measured using the cytokinesis-block micronucleus cytome assay and aneuploidy in human B lymphoblastoid cell lines". Mutagenesis. 26 (3): 421–9. doi:10.1093/mutage/geq110. PMID 21273273. 25. ^ McHale CM, Smith MT, Zhang L (2014). "Application of toxicogenomic profiling to evaluate effects of benzene and formaldehyde: from yeast to human". Ann. N. Y. Acad. Sci. 1310: 74–83. doi:10.1111/nyas.12382. PMC 3978411. PMID 24571325. 26. ^ Xia Y, Bian Q, Xu L, Cheng S, Song L, Liu J, Wu W, Wang S, Wang X (2004). "Genotoxic effects on human spermatozoa among pesticide factory workers exposed to fenvalerate". Toxicology. 203 (1–3): 49–60. doi:10.1016/j.tox.2004.05.018. PMID 15363581. 27. ^ Xia Y, Cheng S, Bian Q, Xu L, Collins MD, Chang HC, Song L, Liu J, Wang S, Wang X (2005). "Genotoxic effects on spermatozoa of carbaryl-exposed workers". Toxicol. Sci. 85 (1): 615–23. doi:10.1093/toxsci/kfi066. PMID 15615886. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Nondisjunction	c1834741	28,511	wikipedia	https://en.wikipedia.org/wiki/Nondisjunction	2021-01-18T19:03:41	{"mesh": ["D009630"], "umls": ["C1834741"], "wikidata": ["Q1414557"]}
In cultured lymphoblasts of Fu-1 phenotype, Tummler et al. (1984) found that alpha-L-fucosidase synthesis during cell growth was proportional to the general amount of protein. On the other hand, in cells derived from persons possessing at least one FUCA2 allele, the amount of enzyme increased progressively during the log-phase of growth. They proposed the existence of a regulatory locus (symbolized FUCT) which maps close to the FUCA locus leading to linkage disequilibrium. The FUCT locus appears to be specific for alpha-L-fucosidase; 4 other lysosomal enzymes showed no similar effects. Studies in inbred strains of mice have shown such regulators of lysosomal enzymes (see review by Paigen, 1979) but none has been demonstrated hitherto in man. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine *[FSH]: Follicle-stimulating hormone	FUCOSIDASE REGULATOR	c1850954	28,512	omim	https://www.omim.org/entry/136830	2019-09-22T16:40:57	{"omim": ["136830"], "synonyms": ["Alternative titles", "ALPHA-L-FUCOSIDASE REGULATOR"]}
Severe combined immunodeficiency (SCID) due to gamma chain deficiency, also called SCID-X1, is a form of SCID (see this term) characterized by severe and recurrent infections, associated with diarrhea and failure to thrive. ## Epidemiology It accounts for approximately 50% of SCID cases and is the most common form of SCID in Europe. The annual incidence varies among the populations but it is estimated at approximately 1/200,000 births. The disease occurs in males. ## Clinical description SCID-X1 manifests during the first months of life with severe and often life threatening viral, bacterial or fungal infections (e.g. Pneumocystis jiroveci pneumonitis, disseminated BCG infection if previously vaccinated), and failure to thrive. Chronic diarrhea is a frequent finding. Some patients may have skin rashes and abnormalities of liver function. Materno-fetal transfusion-associated graft versus host disease is also associated with the disease. Immunological findings are lymphopenia with the absence of T and NK cells, hypogammaglobulinemia, and normal or increased B cell count. ## Etiology SCID-X1 results from a defect in the IL2RG gene encoding the common gamma chain. ## Genetic counseling Transmission is X-linked. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	T-B+ severe combined immunodeficiency due to gamma chain deficiency	c1279481	28,513	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=276	2021-01-23T17:54:37	{"gard": ["5618"], "mesh": ["D053632"], "omim": ["300400"], "umls": ["C2931540"], "icd-10": ["D81.2"], "synonyms": ["SCIDX1", "T-B+ SCID due to gamma chain deficiency", "T-B+ severe combined immunodeficiency, X-linked"]}
Hystrix-like ichthyosis–deafness syndrome SpecialtyDermatology Hystrix-like ichthyosis–deafness syndrome (also known as "HID syndrome"[1]) is a cutaneous condition characterized by a keratoderma.[1] ## See also[edit] * KID syndrome * List of cutaneous conditions ## References[edit] 1. ^ a b Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 1-4160-2999-0. ## External links[edit] Classification D * OMIM: 602540 This dermatology article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Hystrix-like ichthyosis–deafness syndrome	c3665333	28,514	wikipedia	https://en.wikipedia.org/wiki/Hystrix-like_ichthyosis%E2%80%93deafness_syndrome	2021-01-18T19:03:35	{"mesh": ["C580224"], "orphanet": ["477"], "wikidata": ["Q5962435"]}
This article has multiple issues. Please help improve it or discuss these issues on the talk page. (Learn how and when to remove these template messages) This article relies largely or entirely on a single source. Relevant discussion may be found on the talk page. Please help improve this article by introducing citations to additional sources. Find sources: "Philophobia" fear – news · newspapers · books · scholar · JSTOR (August 2016) Some of this article's listed sources may not be reliable. Please help this article by looking for better, more reliable sources. Unreliable citations may be challenged or deleted. (August 2016) (Learn how and when to remove this template message) The topic of this article may not meet Wikipedia's general notability guideline. Please help to demonstrate the notability of the topic by citing reliable secondary sources that are independent of the topic and provide significant coverage of it beyond a mere trivial mention. If notability cannot be shown, the article is likely to be merged, redirected, or deleted. Find sources: "Philophobia" fear – news · newspapers · books · scholar · JSTOR (December 2016) (Learn how and when to remove this template message) (Learn how and when to remove this template message) Philophobia (from Greek "φιλέω-φιλώ" (love) and "φοβία" (phobia)) is the fear of falling in love.[1][2][3] Not included in the DSM-5.[4][5] The risk is usually when a person has confronted any emotional turmoil relating to love but also can be a chronic phobia.[citation needed] This affects the quality of life and pushes a person away from commitment. A negative aspect of this fear of being in love or falling in love is that it keeps a person in solitude. It can also evolve out of religious and cultural beliefs that prohibit love.[citation needed] It represents certain guilt and frustration towards the reaction coming from inside. ## References[edit] 1. ^ Tavormina, Romina (November 2014). "Why are we afraid to love?". Psychiatria Danubina. 26 Suppl 1: 178–183. ISSN 0353-5053. PMID 25413537. 2. ^ "Definition of philophobia \| Dictionary.com". www.dictionary.com. Retrieved 2020-11-03. 3. ^ "philophobia - Wiktionary". en.wiktionary.org. Retrieved 2020-11-03. 4. ^ "What is philophobia?". 5. ^ "What Is Philophobia, and How Can You Manage Fear of Falling in Love?". [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Philophobia (fear)	None	28,515	wikipedia	https://en.wikipedia.org/wiki/Philophobia_(fear)	2021-01-18T19:07:06	{"wikidata": ["Q26352"]}
Polysyndactyly or PPD4 is a form of preaxial polydactyly of fingers (see this term), a limb malformation syndrome, characterized by the presence of a thumb showing the mildest degree of duplication, being broad, bifid or with radially deviated distal phalanx. Syndactyly of various degrees of third-and-fourth fingers is occasionally present. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Polysyndactyly	c0265553	28,516	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93338	2021-01-23T17:04:00	{"gard": ["9903"], "mesh": ["D013576"], "omim": ["174700"], "umls": ["C0265553", "C1868111"], "icd-10": ["Q70.4"], "synonyms": ["PPD4", "Preaxial polydactyly type 4"]}
Severe neonatal lactic acidosis due to NFS1-ISD11 complex deficiency is a rare, hereditary, mitochondrial oxidative phosphorylation disorder characterized by severe neonatal lactic acidosis and deficiency of mitochondrial complexes I, II and III. Clinical features are variable and may include hypotonia, respiratory distress with cyanosis, failure to thrive, feeding difficulties, hypoglycemia, dehydration, vomiting, seizures, and a risk of multiple organ failure. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Severe neonatal lactic acidosis due to NFS1-ISD11 complex deficiency	c3810055	28,517	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=397593	2021-01-23T17:10:15	{"omim": ["615595"], "icd-10": ["E88.8"]}
African histoplasmosis SpecialtyInfectious disease African histoplasmosis is an infection caused by Histoplasma duboisii.[1]:316 Disease has been most often reported in Uganda, Nigeria, Zaire and Senegal. In human disease it manifests differently than histoplasmosis (caused by Histoplasma capsulatum), most often involving the skin and bones and rarely involving the lungs.[2] ## See also[edit] * Histoplasmosis ## References[edit] 1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. 2. ^ "Histoplama capsulatum (Histoplasmosis)". Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 8th Edition. ISBN 978-1-4557-4801-3. ## External links[edit] * Authors at the University of Nigeria have published African histoplasmosis: a review, which includes a thorough reference list. This infection-related cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e * 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	African histoplasmosis	c0153270	28,518	wikipedia	https://en.wikipedia.org/wiki/African_histoplasmosis	2021-01-18T18:56:47	{"umls": ["C0153270"], "wikidata": ["Q4690011"]}
A number sign (#) is used with this entry because Marshall-Smith syndrome (MRSHSS) is caused by heterozygous mutation in the NFIX gene (164005) on chromosome 19p13. Sotos syndrome-2 (SOTOS2; 614753) is also caused by heterozygous mutation in the NFIX gene. Description The Marshall-Smith syndrome is a malformation syndrome characterized by accelerated skeletal maturation, relative failure to thrive, respiratory difficulties, mental retardation, and unusual facies, including prominent forehead, shallow orbits, blue sclerae, depressed nasal bridge, and micrognathia (Adam et al., 2005). Clinical Features Marshall et al. (1971) described 2 infants with a syndrome characterized by accelerated skeletal maturation, failure to thrive, and dysmorphic facial features. Sperli et al. (1993) reviewed 20 reported cases. Chatel et al. (1998) reported an unusually severe form of Marshall-Smith syndrome characterized by neonatal death. Accelerated osseous maturation is a feature of all cases. Diab et al. (2003) emphasized osseous fragility as a clinically significant problem in Marshall-Smith syndrome. Butler (2004) provided a follow-up on the patient with Marshall-Smith syndrome reported by Summers et al. (1999). This child also had osteopenia and fractures without known trauma. His sclerae were blue (a feature typical of patients with Marshall-Smith syndrome) and the eyes were prominent. Skeletal survey at the age of 1 month had shown an estimated bone age of 3 to 4 years in the wrists, elbows, and femoral epiphyses; bone age at 15 months was estimated at 10 years, and at 3.5 years of age, his bone age was 11 years. Adam et al. (2005) commented on the study of Roodhooft et al. (1988) in which a patient with features of Marshall-Smith syndrome was found to have overall small muscle fibers with particularly striking hypoplasia of type IIa and IIb fibers by light microscopy. The patient exhibited persistent gait problems with frequent episodes of fatigue and poor appetite, which prompted the muscle biopsy. Although CT scans of the neck did not detect any muscular abnormalities, the appearance of the bones and spinal cord was not described. The clinical description of weak tendon reflexes, however, did not suggest a diagnosis of cervical spinal stenosis with spinal cord impingement. Cullen et al. (1997) estimated that 24 cases of Marshall-Smith syndrome had been described. Adam et al. (2005) found an additional 9 patients. They summarized the natural history of the disorder on the basis of 5 new cases and reviewed the clinical findings in 3 previously reported children, with special emphasis on skeletal and connective tissue manifestations. An increased rate of nontraumatic fractures and other bony and connective tissue abnormalities supported the hypothesis that the condition should be classified as an osteochondrodysplasia. Adam et al. (2005) noted that most patients with Marshall-Smith syndrome reported in the literature to that time had died in the neonatal period or early infancy, most commonly from respiratory compromise. Sperli et al. (1993) reported long survival of a patient who did not have respiratory complications, and Williams et al. (1997) reported a 3-year-old child whose failure to thrive had been successfully treated, with significant upper airway obstruction but no life-threatening respiratory complications. Adam et al. (2005) concluded that long-term survival is possible if respiratory problems are expectantly and aggressively managed. Shaw et al. (2010) reported 15 new patients with Marshall-Smith syndrome, provided an update on 4 previously reported patients (Williams et al., 1997; Dernedde et al., 1998; Adam et al., 2005; Deshpande et al., 2006), and compared these patients to 43 patients with Marshall-Smith syndrome or a very similar phenotype described in the literature. The primary clinical features were moderate to severe developmental delay with absent or limited speech, unusual behavior such as playing in a repetitive or stereotypic manner with a favorite toy, dysharmonic bone maturation, respiratory compromise secondary to upper airway obstruction, short stature, and kyphoscoliosis. Characteristic facial features included high forehead, underdeveloped midface, proptosis, anteverted nares, and everted lips. Minor abnormalities of brain morphology such as hypoplasia of the corpus callosum were common. Mortality from respiratory complications was high, but Shaw et al. (2010) noted that airway support increasingly allowed survival into adulthood. Molecular Genetics Based on an Nfix-deficient mouse model with a phenotype similar to that in Marshall-Smith syndrome, Malan et al. (2010) screened 9 individuals with MRSHSS for NFIX mutations and found heterozygosity for 7 independent frameshift mutations (164005.0002-164005.0008) and 2 different mutations within the donor splice site of exon 6 (164005.0009-164005.0010). All of the mutations occurred de novo and were not found in 300 control chromosomes. RT-PCR analysis of RNA from skin fibroblasts of 3 patients detected both normal and mutated alleles, suggesting that the mutated RNAs escape nonsense-mediated decay surveillance. Malan et al. (2010) suggested that the splice site mutations have a dominant-negative effect and result in a severe phenotype. INHERITANCE \- Autosomal dominant GROWTH Height \- Accelerated linear growth Weight \- Underweight for length Other \- Failure to thrive HEAD & NECK Face \- Prominent forehead \- Micrognathia \- Midface hypoplasia \- Short philtrum \- Prominent premaxilla \- Retrognathia Ears \- Deafness \- Low-set ears \- Overfolded helices Eyes \- Shallow orbits \- Prominent eyes \- Bluish sclerae \- Bushy eyebrows \- Synophrys Nose \- Upturned nose \- Flat nasal bridge \- Short nose \- Anteverted nares Mouth \- Glossoptosis \- Everted lips \- Gum hypertrophy Teeth \- Irregular dentition CARDIOVASCULAR Heart \- Atrial septal defect Vascular \- Patent ductus arteriosus RESPIRATORY Nasopharynx \- Choanal stenosis \- Choanal atresia \- Obstructive sleep apnea Larynx \- Laryngomalacia Airways \- Rudimentary epiglottis Lung \- Apnea \- Aspiration pneumonia \- Pulmonary hypertension CHEST Ribs Sternum Clavicles & Scapulae \- Short sternum \- Thick clavicles \- Large sternal ossification centers \- Pectus excavatum ABDOMEN External Features \- Umbilical hernia \- Omphalocele SKELETAL \- Accelerated skeletal maturation (bone age of 4 at birth) Skull \- Long cranium \- Prominent frontal bone \- Underdeveloped mandibular rami Spine \- Scoliosis \- Odontoid hypoplasia \- Atlantoaxial subluxation Limbs \- Thin long bones Hands \- Wide proximal and middle phalanges \- Bullet-shaped middle phalanges \- Narrow distal phalanges \- Distal widening of metacarpals SKIN, NAILS, & HAIR Hair \- Hypertrichosis NEUROLOGIC Central Nervous System \- Motor retardation \- Mental retardation \- Hypotonia \- Macrogyria \- Cerebral atrophy \- Absent corpus callosum \- Spinal stenoses MISCELLANEOUS \- Early death \- De novo mutation MOLECULAR BASIS \- Caused by mutation in the nuclear factor I/X gene (NFIX, 164005.0002 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	MARSHALL-SMITH SYNDROME	c0265211	28,519	omim	https://www.omim.org/entry/602535	2019-09-22T16:13:37	{"doid": ["0050858"], "mesh": ["C536026"], "omim": ["602535"], "orphanet": ["561"]}
Acinic cell carcinoma Micrograph of an acinic cell carcinoma (right of image) and acinar glands (parotid gland \- left of image). H&E stain. SpecialtyENT surgery Acinic cell carcinoma is a malignant tumor representing 2% of all salivary tumors. 90% of the time found in the parotid gland, 10% intraorally on buccal mucosa or palate. The disease presents as a slow growing mass, associated with pain or tenderness in 50% of the cases. Often appears pseudoencapsulated. ## Contents * 1 Diagnosis * 2 Prognosis * 3 Treatment * 4 Epidemiology * 5 Acinic cell carcinoma of the lung * 6 References * 7 External links ## Diagnosis[edit] Basophilic, bland cells similar to acinar cells. Growth pattern: solid - acinar cells, microcytic - small cystic spaces mucinous or eosinophilic, papillary-cystic - large cystic lined by epithelium, follicular - similar to thyroid tissue. These tumors, which resemble serous acinar cells, vary in their behavior from locally aggressive to blatantly malignant. It can also appear in the breast. The pancreatic form of acinic cell carcinoma is a rare subtype of exocrine pancreatic cancer. Exocrine pancreatic cancers are the most common form of pancreatic cancer when compared to endocrine pancreatic cancer.[1] Acinic cell carcinomas arise most frequently in the parotid gland. Other sites of primary tumors have included the submandibular gland and other major and minor salivary glands. There have been rare cases of primary tumors involving the parapharyngeal space and the sublingual gland.[2][3] * Micrograph of acinic cell carcinoma. Pap stain. Fine needle aspiration specimen. * Intermed. mag. * Very high mag. ## Prognosis[edit] Prognosis is good for acinic cell carcinoma of the parotid gland, with five-year survival rates approaching 90%, and 20-year survival exceeding 50%. Patients with acinic cell carcinomas with high grade transformation (sometimes also called dedifferentiation) have significantly worse survival.[3][4] The prognosis of an acinic cell carcinoma originating in the lung is much more guarded than cases of this rare histotype occurring in most other organs, but is still considerably better than for other types of lung cancer.[5] ## Treatment[edit] a) Surgical resection is mainstay of treatment, whenever possible. If tumor is completely removed, post-operative radiation therapy is typically not needed since acinic cell is considered a low-grade histology. Post-operative radiation therapy for acinic cell carcinoma is used if: 1) margins are positive, 2) incomplete resection, 3) tumor invades beyond gland, 4) positive lymph nodes. b) Neutron beam radiation c) Conventional radiation d) Chemotherapy [2] ## Epidemiology[edit] Acinic cell carcinoma appears in all age groups, but presents at a younger median age (approx. 52 years) than most other salivary gland cancers. Occurrences in children are quite common.[2] ## Acinic cell carcinoma of the lung[edit] Acinic cell carcinoma of the lung is a very rare variant of lung cancer that, in this organ, is classified among the salivary gland-like carcinoma of the lung. Fewer than 1% of malignancies beginning in the lower respiratory tract are acinic cell carcinomas.[5] ## References[edit] 1. ^ Coyne JD, Dervan PA (July 2002). "Primary acinic cell carcinoma of the breast". J. Clin. Pathol. 55 (7): 545–7. doi:10.1136/jcp.55.7.545. PMC 1769684. PMID 12101208. 2. ^ a b c "Acinic Cell Carcinoma Overview Archived 2009-12-15 at the Wayback Machine." Acinic Cell Carcinoma Information Center. Web. 07 Dec. 2009. 3. ^ a b Chiosea, SI; Griffith, C; Assaad, A; Seethala, RR (March 2012). "The profile of acinic cell carcinoma after recognition of mammary analog secretory carcinoma". The American Journal of Surgical Pathology. 36 (3): 343–50. doi:10.1097/pas.0b013e318242a5b0. PMID 22301503. 4. ^ Thompson, LDR; Aslam, MN; Stall, JN; Udager, AM; Chiosea, S; McHugh, JB (June 2016). "Clinicopathologic and Immunophenotypic Characterization of 25 Cases of Acinic Cell Carcinoma with High-Grade Transformation". Head and Neck Pathology. 10 (2): 152–160. doi:10.1007/s12105-015-0645-x. PMC 4838973. PMID 26245749. 5. ^ a b Travis, William D; Brambilla, Elisabeth; Muller-Hermelink, H Konrad; Harris, Curtis C, eds. (2004). Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart (PDF). World Health Organization Classification of Tumours. Lyon: IARC Press. ISBN 92-832-2418-3. Archived from the original (PDF) on 2009-08-23. Retrieved 27 March 2010. ## External links[edit] Classification D * ICD-10: C07 * ICD-9-CM: 142.0 * ICD-O: M8550/3 * Thompson, L.D.R. (2016), Diagnostic Pathology: Head and Neck, 2 ed, Elsevier, ISBN 978-0323392556 * Neville, Brad W. (2002). Oral & maxillofacial pathology (2nd ed.). Philadelphia: W.B. Saunders. ISBN 0-7216-9003-3. * Kahn, Michael A. Basic Oral and Maxillofacial Pathology. Volume 1. 2001. * v * t * e Glandular and epithelial cancer Epithelium Papilloma/carcinoma * Small-cell carcinoma * Combined small-cell carcinoma * Verrucous carcinoma * Squamous cell carcinoma * Basal-cell carcinoma * Transitional cell carcinoma * Inverted papilloma Complex epithelial * Warthin's tumor * Thymoma * Bartholin gland carcinoma Glands Adenomas/ adenocarcinomas Gastrointestinal * tract: Linitis plastica * Familial adenomatous polyposis * pancreas * Insulinoma * Glucagonoma * Gastrinoma * VIPoma * Somatostatinoma * Cholangiocarcinoma * Klatskin tumor * Hepatocellular adenoma/Hepatocellular carcinoma Urogenital * Renal cell carcinoma * Endometrioid tumor * Renal oncocytoma Endocrine * Prolactinoma * Multiple endocrine neoplasia * Adrenocortical adenoma/Adrenocortical carcinoma * Hürthle cell Other/multiple * Neuroendocrine tumor * Carcinoid * Adenoid cystic carcinoma * Oncocytoma * Clear-cell adenocarcinoma * Apudoma * Cylindroma * Papillary hidradenoma Adnexal and skin appendage * sweat gland * Hidrocystoma * Syringoma * Syringocystadenoma papilliferum Cystic, mucinous, and serous Cystic general * Cystadenoma/Cystadenocarcinoma Mucinous * Signet ring cell carcinoma * Krukenberg tumor * Mucinous cystadenoma / Mucinous cystadenocarcinoma * Pseudomyxoma peritonei * Mucoepidermoid carcinoma Serous * Ovarian serous cystadenoma / Pancreatic serous cystadenoma / Serous cystadenocarcinoma / Papillary serous cystadenocarcinoma Ductal, lobular, and medullary Ductal carcinoma * Mammary ductal carcinoma * Pancreatic ductal carcinoma * Comedocarcinoma * Paget's disease of the breast / Extramammary Paget's disease Lobular carcinoma * Lobular carcinoma in situ * Invasive lobular carcinoma Medullary carcinoma * Medullary carcinoma of the breast * Medullary thyroid cancer Acinar cell * Acinic cell carcinoma * v * t * e Tumors of lip, oral cavity and pharynx / head and neck cancer Oral cancer Salivary gland malignant epithelial tumors * Acinic cell carcinoma * Mucoepidermoid carcinoma * Adenoid cystic carcinoma * Salivary duct carcinoma * Epithelial-myoepithelial carcinoma * Polymorphous low-grade adenocarcinoma * Hyalinizing clear cell carcinoma benign epithelial tumors * Pleomorphic adenoma * Warthin's tumor ungrouped: * Oncocytoma Tongue * Leukoplakia * Rhabdomyoma * Oropharynx [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Acinic cell carcinoma	c0279738	28,520	wikipedia	https://en.wikipedia.org/wiki/Acinic_cell_carcinoma	2021-01-18T19:00:37	{"umls": ["C0279738"], "wikidata": ["Q55780150"]}
Type of progressive dementia Not to be confused with Lewy body dementia, an umbrella encompassing Parkinson's disease dementia as well as dementia with Lewy bodies. Dementia with Lewy bodies Other namesDiffuse Lewy body disease, dementia due to Lewy body disease Microscopic image of Lewy bodies SpecialtyNeurology, psychiatry SymptomsDementia, abnormal behavior during REM sleep, fluctuations in alertness, visual hallucinations, parkinsonism[1] Usual onsetAfter the age of 50,[2] median 76[3] DurationLong term[4] CausesUnknown[4] Diagnostic methodBased on symptoms and biomarkers[1] Differential diagnosisAlzheimer's, Parkinson's disease dementia, certain mental illnesses, vascular dementia[5] MedicationAcetylcholinesterase inhibitors such as donepezil and rivastigmine;[6] melatonin[7] PrognosisAverage survival 8 years from diagnosis[4] FrequencyAbout 0.4% of persons older than 65[8] Dementia with Lewy bodies (DLB) is a type of dementia accompanied by changes in sleep, behavior, cognition, movement, and autonomic bodily functions. Memory loss is not always an early symptom. The disease worsens over time and is usually diagnosed when cognitive decline interferes with normal daily functioning. Together with Parkinson's disease dementia, DLB is one of the two Lewy body dementias. It is a common form of dementia, but the prevalence is not known accurately and many diagnoses are missed. The disease was first described by Kenji Kosaka in 1976. REM sleep behavior disorder (RBD)—in which people lose the muscle paralysis that normally occurs during REM sleep and act out their dreams—is a core feature. RBD may appear years or decades before other symptoms. Other core features are visual hallucinations, marked fluctuations in attention or alertness, and parkinsonism (slowness of movement, trouble walking, or rigidity). Not all features must be present for a diagnosis. Definitive diagnosis usually requires an autopsy, but a likely diagnosis is made based on symptoms and tests which may include blood tests, neuropsychological tests, imaging, and sleep studies. Most people with DLB do not have affected family members, although occasionally DLB runs in a family. The exact cause is unknown, but involves widespread deposits of abnormal clumps of protein that form in neurons of the diseased brain. Known as Lewy bodies (discovered in 1912 by Frederic Lewy) and Lewy neurites, these clumps affect both the central nervous system and the autonomic nervous system. Heart function and every level of gastrointestinal function—from chewing to defecation—can be affected, constipation being one of the most common symptoms. Low blood pressure upon standing can also be a symptom. DLB also affects behavior; mood changes such as depression and apathy are common. DLB typically begins after the age of fifty[2] and people with the disease have a life expectancy of about eight years after diagnosis.[4] There is no cure or medication to stop the disease from progressing, and people in the latter stages of DLB may be unable to care for themselves. Treatments aim to relieve some of the symptoms and reduce the burden on caregivers. Medicines such as donepezil and rivastigmine are effective at improving cognition and overall functioning, and melatonin can be used for sleep-related symptoms.[9] Antipsychotics are usually avoided, even for hallucinations, because severe and life-threatening reactions occur in almost half of people with DLB,[10] and their use can result in death.[11] Management of the many different symptoms is challenging, as it involves multiple specialties and education of caregivers. ## Contents * 1 Classification * 2 Signs and symptoms * 2.1 Essential feature * 2.2 Core features * 2.2.1 Fluctuating cognition, alertness or attention * 2.2.2 REM sleep behavior disorder * 2.2.3 Parkinsonism * 2.2.4 Visual hallucinations * 2.3 Supportive features * 3 Causes * 4 Pathophysiology * 5 Diagnosis * 5.1 Criteria * 5.2 Clinical history and testing * 5.3 Differential * 5.3.1 Alzheimer's disease * 5.3.2 Synucleinopathies * 5.3.3 Frontotemporal dementias * 6 Management * 6.1 Medication * 6.1.1 Cognitive symptoms * 6.1.2 Motor symptoms * 6.1.3 Neuropsychiatric symptoms * 6.1.4 Sleep disorders * 6.1.5 Autonomic symptoms * 6.2 Other * 6.3 Caregiving * 7 Prognosis * 8 Epidemiology * 9 History * 10 Society and culture * 11 Research directions * 12 Notes * 13 References * 13.1 Works cited * 14 External links ## Classification[edit] Dementia with Lewy bodies (DLB) is a type of dementia that is progressive and neurodegenerative;[12] that is, it is characterized by degeneration of the central nervous system that worsens over time. Dementia with Lewy bodies is sometimes classified in other ways. It is one of the two Lewy body dementias, along with Parkinson's disease dementia.[13] The atypical parkinsonian syndromes include DLB, along with other conditions.[14] Lastly, DLB is a synucleinopathy, meaning that it is characterized by abnormal deposits of alpha-synuclein protein in the brain. The synucleinopathies include Parkinson's disease, multiple system atrophy, and other rarer conditions.[15] ## Signs and symptoms[edit] DLB is dementia that occurs with "some combination of fluctuating cognition, recurrent visual hallucinations, rapid eye movement (REM) sleep behavior disorder (RBD), and parkinsonism starting with or after the dementia diagnosis", according to Armstrong (2019).[16] DLB has widely varying symptoms and is more complex than many other dementias.[17][18] Several areas of functioning can be affected by Lewy pathology,[a] in which the alpha-synuclein deposits that cause DLB damage many different regions of the nervous system (such as the autonomic nervous system and numerous regions of the brain).[19] In DLB, there is an identifiable set of early signs and symptoms; these are called the prodromal, or pre-dementia, phase of the disease.[20] These early signs can appear 15 years or more before dementia develops.[20] The earliest signs are constipation and dizziness from autonomic dysfunction, hyposmia (reduced ability to smell), visual hallucinations, and RBD.[21] RBD may appear years or decades before other symptoms.[22] Memory loss is not always an early symptom.[23] The symptoms can be divided into essential, core, and supportive features.[1] Dementia is the essential feature and must be present for diagnosis, while core and supportive features are further evidence in support of diagnosis (see diagnostic criteria below).[24] ### Essential feature[edit] A dementia diagnosis is made after cognitive decline progresses to a point of interfering with normal daily activities, or social or occupational function.[24] While dementia is an essential feature of DLB, it does not always appear early on, and is more likely to present as the condition progresses.[24][25] ### Core features[edit] While specific symptoms may vary, the core features of DLB are fluctuating cognition, alertness or attention; REM sleep behavior disorder; one or more of the cardinal features of parkinsonism, not due to medication or stroke; and repeated visual hallucinations.[1] The 2017 Fourth Consensus Report of the DLB Consortium determined these to be core features based on the availability of high-quality evidence indicating they are highly specific to the condition.[24] #### Fluctuating cognition, alertness or attention[edit] Besides memory loss, the three most common cognitive symptoms in DLB are impairments of attention, executive function, and visuospatial function.[26] These impairments are present early in the course of the disease.[24] Individuals with DLB may be easily distracted, have a hard time focusing on tasks,[27] or appear to be "delirium-like", "zoning out", or in states of altered consciousness[24][28] with spells of confusion, agitation or incoherent speech.[29] They may have disorganized speech and their ability to organize their thoughts may change during the day.[5][24] Executive function describes attentional and behavioral controls, memory and cognitive flexibility that aid problem solving and planning.[30] Problems with executive function surface in activities requiring planning and organizing.[8] Deficits can manifest in impaired job performance, inability to follow conversations, difficulties with multitasking, or mistakes in driving, such as misjudging distances or becoming lost.[31] The person with DLB may experience disorders of wakefulness or sleep disorders (in addition to REM sleep behavior disorder) that can be severe.[22] These disorders include daytime sleepiness, drowsiness or napping more than two hours a day, insomnia, periodic limb movements, restless legs syndrome and sleep apnea.[22] #### REM sleep behavior disorder[edit] REM sleep behavior disorder and dementia with Lewy bodies "REM sleep behavior disorder (RBD) has been studied more thoroughly in correlation with DLB and is now considered a core feature. ... Basically, dementia in the presence of polysomnogram-confirmed RBD suggests possible DLB." —B. Tousi (2017), Diagnosis and Management of Cognitive and Behavioral Changes in Dementia With Lewy Bodies.[32] REM sleep behavior disorder (RBD) is a parasomnia in which individuals lose the paralysis of muscles (atonia) that is normal during rapid eye movement (REM) sleep, and consequently act out their dreams or make other abnormal movements or vocalizations.[33] About 80% of those with DLB have RBD.[34] Abnormal sleep behaviors may begin before cognitive decline is observed,[24] and may appear decades before any other symptoms, often as the first clinical indication of DLB and an early sign of a synucleinopathy.[35] On autopsy, 94 to 98% of individuals with polysomnography-confirmed RBD have a synucleinopathy—most commonly DLB or Parkinson's disease[36][37] in about equal proportions.[38] More than three out of four people with RBD are diagnosed with a neurodegenerative condition within ten years,[39] but additional neurodegenerative diagnoses may emerge up to 50 years after RBD diagnosis.[37] RBD may subside over time.[24] Individuals with RBD may not be aware that they act out their dreams.[40] RBD behaviors may include yelling, screaming, laughing, crying, unintelligible talking, nonviolent flailing, or more violent punching, kicking, choking, or scratching.[41][42] The reported dream enactment behaviors are frequently violent,[43] and involve a theme of being chased or attacked.[36] People with RBD may fall out of bed or injure themselves or their bed partners,[24][36][42] which may cause bruises, fractures, or subdural hematomae.[44] Because people are more likely to remember or report violent dreams and behaviors—and to be referred to a specialist when injury occurs—recall or selection bias may explain the prevalence of violence reported in RBD.[45] #### Parkinsonism[edit] Parkinsonism is a clinical syndrome characterized by slowness of movement, rigidity, postural instability, and tremor;[46][47] it is found in DLB and many other conditions like Parkinson's disease, Parkinson's disease dementia, and others.[47] Parkinsonism occurs in more than 85% of people with DLB, who may have one or more of these cardinal features,[24] although tremor at rest is less common.[48] Motor symptoms may include shuffling gait, problems with balance, falls, blank expression, reduced range of facial expression, and low speech volume or a weak voice.[2] Presentation of motor symptoms is variable, but they are usually symmetric, presenting on both sides of the body.[49] Only one of the cardinal symptoms of parkinsonism may be present,[1] and the symptoms may be less severe than in persons with Parkinson's disease.[50] #### Visual hallucinations[edit] Up to 80% of people with DLB have visual hallucinations, typically early in the course of the disease.[24][51] They are recurrent and frequent; may be scenic, elaborate and detailed;[52] and usually involve animated perceptions of animals or people, including children and family members.[5] Examples of visual hallucinations "vary from 'little people' who casually walk around the house, 'ghosts' of dead parents who sit quietly at the bedside, to 'bicycles' that hang off of trees in the back yard".[53] These hallucinations can sometimes provoke fear, although their content is more typically neutral.[5] In some cases, the person with DLB may have insight that the hallucinations are not real.[54] Among those with more disrupted cognition, the hallucinations can become more complex, and they may be less aware that their hallucinations are not real.[55] Visual misperceptions or illusions are also common in DLB but differ from visual hallucinations. While visual hallucinations occur in the absence of real stimuli, visual illusions occur when real stimuli are incorrectly perceived;[55] for example, a person with DLB may misinterpret a floor lamp for a person.[5] ### Supportive features[edit] Supportive features of DLB have less diagnostic weight, but they provide evidence for the diagnosis.[24] Supportive features may be present early in the progression, and persist over time; they are common but they are not specific to the diagnosis. The supportive features are:[1] * marked sensitivity to antipsychotics (neuroleptics);[1] * marked dysautonomia (autonomic dysfunction) in which the autonomic nervous system does not work properly;[1] * hallucinations in senses other than vision[1] (hearing, touch, taste, and smell;[56] * hypersomnia (excessive sleepiness);[1] * hyposmia (reduced ability to smell);[1] * false beliefs and delusions organized around a common theme;[1] * postural instability, loss of consciousness, and frequent falls;[1][28] * apathy, anxiety, or depression.[1][28] People with DLB are very sensitive to antipsychotic medications like haloperidol,[26] which carry an increased risk of morbidity and mortality in DLB.[9][57][58] Partly because of loss of cells that release the neurotransmitter dopamine, people with DLB may have neuroleptic malignant syndrome, impairments in cognition or alertness, or irreversible exacerbation of parkinsonism including severe rigidity,[43] and dysautonomia from the use of antipsychotics.[58] Dysautonomia (autonomic dysfunction) occurs when Lewy pathology affects the peripheral autonomic nervous system (the nerves that serve organs such as the intestines, heart, and urinary tract).[19] The first signs of autonomic dysfunction are often subtle.[45] Symptoms include blood pressure problems such as orthostatic hypotension (dizziness after standing up) and supine hypertension;[59] constipation,[60] urinary problems,[61] and sexual dysfunction;[62] loss of or reduced ability to smell;[45][63] and excessive sweating, drooling, or salivation, and problems swallowing (dysphagia).[63][64] Alpha-synuclein deposits can affect cardiac muscle and blood vessels.[65] "Degeneration of the cardiac sympathetic nerves is a neuropathological feature" of the Lewy body dementias, according to Yamada et al.[66] Almost all people with synucleinopathies have cardiovascular dysfunction, although most are asymptomatic.[67] Between 50 and 60% of individuals with DLB have orthostatic hypotension due to reduced blood flow, which can result in lightheadedness, feeling faint, and blurred vision.[65] From chewing to defecation, alpha-synuclein deposits affect every level of gastrointestinal function.[68][69] Almost all persons with DLB have upper gastrointestinal tract dysfunction (such as gastroparesis, delayed gastric emptying) or lower gastrointestinal dysfunction (such as constipation and prolonged stool transit time).[69] Persons with Lewy body dementia almost universally experience nausea, gastric retention, or abdominal distention from delayed gastric emptying.[69] Problems with gastrointestinal function can affect medication absorption.[68] Constipation can present a decade before diagnosis,[70] and is one of the most common symptoms for people with Lewy body dementia.[68] Dysphagia is milder than in other synucleinopathies and presents later.[71] Urinary difficulties (urinary retention, waking at night to urinate, increased urinary frequency and urgency, and over- or underactive bladder) typically appear later and may be mild or moderate.[72] Sexual dysfunction usually appears early in synucleinopathies, and may include erectile dysfunction and difficulty achieving orgasm or ejaculating.[62] Among the other supportive features, psychiatric symptoms are often present when the individual first comes to clinical attention and are more likely, compared to AD, to cause more impairment.[73] About one-third of people with DLB have depression, and they often have anxiety as well.[10] Anxiety leads to increased risk of falls,[74] and apathy may lead to less social interaction.[2] Agitation, behavioral disturbances,[75] and delusions typically appear later in the course of the disease.[5] Delusions may have a paranoid quality, involving themes like a house being broken in to, infidelity,[5] or abandonment.[56] Individuals with DLB who misplace items may have delusions about theft.[5] Capgras delusion may occur, in which the person with DLB loses knowledge of the spouse, caregiver, or partner's face,[76] and is convinced that an imposter has replaced them.[5] Hallucinations in other modalities are sometimes present, but are less frequent.[56] Sleep disorders (disrupted sleep cycles, sleep apnea, and arousal from periodic limb movement disorder) are common in DLB and may lead to hypersomnia.[77] Loss of sense of smell may occur several years before other symptoms.[21] ## Causes[edit] A ribbon diagram of apolipoprotein E. Variants of this protein influence the risk of developing DLB.[78] Like other synucleinopathies,[79] the exact cause of DLB is unknown.[80] Synucleinopathies are typically caused by interactions of genetic and environmental influences.[79] Most people with DLB do not have affected family members, although occasionally DLB runs in a family.[4] The heritability of DLB is thought to be around 30% (that is, about 70% of traits associated with DLB are not inherited).[81] There is overlap in the genetic risk factors for DLB, Alzheimer's disease (AD), Parkinson's disease, and Parkinson's disease dementia.[78][82] The APOE gene has three common variants. One, APOE ε4, is a risk factor for DLB and Alzheimer's disease, whereas APOE ε2 may be protective against both.[78][83] Mutations in GBA, a gene for a lysosomal enzyme, are associated with both DLB and Parkinson's disease.[84] Rarely, mutations in SNCA, the gene for alpha-synuclein, or LRRK2, a gene for a kinase enzyme, can cause any of DLB, Alzheimer's disease, Parkinson's disease or Parkinson's disease dementia.[78] This suggests some shared genetic pathology may underlie all four diseases.[78] The greatest risk of developing DLB is being over the age of 50. Having REM sleep behavior disorder or Parkinson's disease confers a higher risk for developing DLB. Risk of developing DLB has not been linked to any specific lifestyle factors.[2] Risk factors for rapid conversion of RBD to a synucleinopathy include impairments in color vision or the ability to smell, mild cognitive impairment, and abnormal dopaminergic imaging.[85] ## Pathophysiology[edit] This photomicrograph shows brown-immunostained alpha-synuclein in Lewy bodies (large clumps) and Lewy neurites (thread-like structures) in the neocortical tissue of a person who died with Lewy body disease. DLB is characterized by the development of abnormal collections of alpha-synuclein protein within diseased brain neurons, known as Lewy bodies and Lewy neurites.[78] When these clumps of protein form, neurons function less optimally and eventually die.[18] Neuronal loss in DLB leads to profound dopamine dysfunction[86] and marked cholinergic pathology;[87] other neurotransmitters might be affected, but less is known about them.[88] Damage in the brain is widespread, and affects many domains of functioning.[18][a] Loss of acetylcholine-producing neurons is thought to account for degeneration in memory and learning, while the death of dopamine-producing neurons appears to be responsible for degeneration of behavior, cognition, mood, movement, motivation, and sleep.[2] The extent of Lewy body neuronal damage is a key determinant of dementia in the Lewy body disorders.[90][91] The precise mechanisms contributing to DLB are not well understood and are a matter of some controversy.[92] The role of alpha-synuclein deposits is unclear, because individuals with no signs of DLB have been found on autopsy to have advanced alpha-synuclein pathology.[78] The relationship between Lewy pathology and widespread cell death is contentious.[92] It is not known if the pathology spreads between cells or follows another pattern.[93] The mechanisms that contribute to cell death, how the disease advances through the brain, and the timing of cognitive decline are all poorly understood.[92] There is no model to account for the specific neurons and brain regions that are affected.[92] Autopsy studies and amyloid imaging studies using Pittsburgh compound B (PiB)[94] indicate that tau protein pathology and amyloid plaques,[95] which are hallmarks of AD,[96] are also common in DLB[97] and more common than in Parkinson's disease dementia.[98] Amyloid-beta (Aβ) deposits are found in the tauopathies—neurodegenerative diseases characterized by neurofibrillary tangles of hyperphosphorylated tau protein[96][99][100]—but the mechanism underlying dementia is often mixed, and Aβ is also a factor in DLB.[101] A proposed pathophysiology for RBD implicates neurons in the reticular formation that regulate REM sleep. RBD might appear decades earlier than other symptoms in the Lewy body dementias because these cells are affected earlier, before spreading to other brain regions.[41] ## Diagnosis[edit] Dementia with Lewy bodies can only be definitively diagnosed after death with an autopsy of the brain (or in rare familial cases, via a genetic test),[2] so diagnosis of the living is referred to as probable or possible.[24] Diagnosing DLB can be challenging because of the wide range of symptoms with differing levels of severity in each individual.[3] DLB is often misdiagnosed[102] or, in its early stages, confused with Alzheimer’s disease.[103] As many as one in three diagnoses of DLB may be missed.[104] Another complicating factor is that DLB can occur along with AD; autopsy reveals that most people with DLB have some level of changes attributed to AD in their brains, which contributes to the wide-ranging variety of symptoms and diagnostic difficulty.[3][105][106] Despite the difficulty in diagnosis, a prompt diagnosis is important because of the serious risks of sensitivity to antipsychotics and the need to inform both the person with DLB and the person's caregivers about those medications' side effects.[57][107] The management of DLB is difficult in comparison to many other neurodegenerative diseases, so an accurate diagnosis is important.[17] ### Criteria[edit] The 2017 Fourth Consensus Report established diagnostic criteria for probable and possible DLB, recognizing advances in detection since the earlier Third Consensus (2005)[108] version.[b] The 2017 criteria are based on essential, core, and supportive clinical features, and diagnostic biomarkers.[1] The essential feature is dementia; for a DLB diagnosis, it must be significant enough to interfere with social or occupational functioning.[24] The four core clinical features (described in the Signs and symptoms section) are fluctuating cognition, visual hallucinations, REM sleep behavior disorder, and signs of parkinsonism. Supportive clinical features are marked sensitivity to antipsychotics; marked autonomic dysfunction; nonvisual hallucinations; hypersomnia; reduced ability to smell; false beliefs and delusions organized around a common theme; postural instability, loss of consciousness and frequent falls; and apathy, anxiety, or depression.[1][28] Positron emission tomography, for example, using PiB is helpful in the diagnosis of DLB.[24][94] Direct laboratory-measurable biomarkers for DLB diagnosis are not known, but several indirect methods can lend further evidence for diagnosis.[24] The indicative diagnostic biomarkers are: reduced dopamine transporter uptake in the basal ganglia shown on PET or SPECT imaging; low uptake of 123iodine-metaiodobenzylguanidine (123I-MIBG) shown on myocardial scintigraphy; and loss of atonia during REM sleep evidenced on polysomnography. Supportive diagnostic biomarkers (from PET, SPECT, CT, or MRI brain imaging studies or EEG monitoring) are: lack of damage to medial temporal lobe; reduced occipital activity; and prominent slow-wave activity.[24] Probable DLB can be diagnosed when dementia and at least two core features are present, or when one core feature and at least one indicative biomarker are present. Possible DLB can be diagnosed when dementia and only one core feature are present or, if no core features are present, then at least one indicative biomarker is present.[24][110] DLB is distinguished from Parkinson's disease dementia by the time frame in which dementia symptoms appear relative to parkinsonian symptoms. DLB is diagnosed when cognitive symptoms begin before or at the same time as parkinsonian motor signs. Parkinson's disease dementia would be the diagnosis when Parkinson's disease is well established before the dementia occurs (the onset of dementia is more than a year after the onset of parkinsonian symptoms).[111] DLB is listed in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) as major or mild neurocognitive disorder with Lewy bodies.[78] The differences between the DSM and DLB Consortium diagnostic criteria are: 1) the DSM does not include low dopamine transporter uptake as a supportive feature, and 2) unclear diagnostic weight is assigned to biomarkers in the DSM.[64] Lewy body dementias are classified by the World Health Organization in its ICD-10, the International Statistical Classification of Diseases and Related Health Problems, in chapter VI, as diseases of the nervous system, code 31.8.[112] ### Clinical history and testing[edit] Diagnostic tests can be used to establish some features of the condition and distinguish them from symptoms of other conditions. Diagnosis may include taking the person's medical history, a physical exam, assessment of neurological function, testing to rule out conditions that may cause similar symptoms, brain imaging, neuropsychological testing to assess cognitive function,[2][113] sleep studies, or myocardial scintigraphy.[24] Laboratory testing can rule out other conditions that can cause similar symptoms, such as abnormal thyroid function, syphilis, HIV, or vitamin deficiencies that may cause symptoms similar to dementia.[113][114] Dementia screening tests are the Mini-Mental State Examination and the Montreal Cognitive Assessment.[26] For tests of attention, digit span, serial sevens, and spatial span can be used for simple screening, and the Revised Digit Symbol Subtest of the Wechsler Adult Intelligence Scale may show defects in attention that are characteristic of DLB.[115] The Frontal Assessment Battery, Stroop test and Wisconsin Card Sorting Test are used for evaluation of executive function, and there are many other screening instruments available.[116] Adult connected to wires from sensors for polysomnography If DLB is suspected when parkinsonism and dementia are the only presenting features, PET or SPECT imaging may show reduced dopamine transporter activity. A DLB diagnosis may be warranted if other conditions with reduced dopamine transporter uptake can be ruled out.[24] RBD is diagnosed either by sleep study recording or, when sleep studies cannot be performed, by medical history and validated questionnaires.[24][44][c] In individuals with dementia and a history of RBD, a probable DLB diagnosis can be justified (even with no other core feature or biomarker) based on a sleep study showing REM sleep without atonia because it is so highly predictive.[24] Conditions similar to RBD, like severe sleep apnea and periodic limb movement disorder, must be ruled out.[24] Prompt evaluation and treatment of RBD is indicated when a prior history of violence or injury is present as it may increase the likelihood of future violent dream enactment behaviors.[42] Individuals with RBD may not be able to provide a history of dream enactment behavior, so bed partners are also consulted.[24][45] The REM Sleep Behavior Disorder Single-Question Screen offers diagnostic sensitivity and specificity in the absence of polysomnography with one question:[44] "Have you ever been told, or suspected yourself, that you seem to 'act out your dreams' while asleep (for example, punching, flailing your arms in the air, making running movements, etc.)?"[117] Because some individuals with DLB do not have RBD, normal findings from a sleep study can not rule out DLB.[118] Since 2001, 123iodine-metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy has been used diagnostically in East Asia (principally Japan), but not in the United States.[32][119][120] MIBG is taken up by sympathetic nerve endings, such as those that innervate the heart, and is labeled for scintigraphy with radioactive 123iodine.[120] Autonomic dysfunction resulting from damage to nerves in the heart in patients with DLB is associated with lower cardiac uptake of 123I-MIBG.[120] There is no genetic test to determine if an individual will develop DLB[2][24] and, according to the Lewy Body Dementia Association, genetic testing is not routinely recommended because there are only rare instances of hereditary DLB.[121] ### Differential[edit] Many neurodegenerative conditions share cognitive and motor symptoms with dementia with Lewy bodies. The differential diagnosis includes Alzheimer's disease; such synucleinopathies as Parkinson's disease dementia, Parkinson's disease, and multiple system atrophy; vascular dementia; and progressive supranuclear palsy, corticobasal degeneration, and corticobasal syndrome.[5] The symptoms of DLB are easily confused with delirium,[122] or more rarely as psychosis;[103] prodromal subtypes of delirium-onset DLB and psychiatric-onset DLB have been proposed.[20] Mismanagement of delirium is a particular concern because of the risks to people with DLB associated with antipsychotics.[122] A careful examination for features of DLB is warranted in individuals with unexplained delirium.[123] PET or SPECT imaging showing reduced dopamine transporter uptake can help distinguish DLB from delirium.[122] Lewy pathology affects the peripheral autonomic nervous system; autonomic dysfunction is observed less often in AD, frontotemporal, or vascular dementias, so its presence can help differentiate them.[124] MRI scans almost always show abnormalities in the brains of people with vascular dementia, which can begin suddenly.[125] #### Alzheimer's disease[edit] DLB is distinguishable from AD even in the prodromal phase.[21] Short-term memory impairment is seen early in AD and is a prominent feature, while fluctuating attention is uncommon; impairment in DLB is more often seen first as fluctuating cognition.[126] In contrast to AD—in which the hippocampus is among the first brain structures affected, and episodic memory loss related to encoding of memories is typically the earliest symptom—memory impairment occurs later in DLB.[31][127] People with amnestic mild cognitive impairment (in which memory loss is the main symptom) may progress to AD, whereas those with non-amnestic mild cognitive impairment (which has more prominent impairments in language, visuospatial, and executive domains) are more likely to progress towards DLB.[128] Memory loss in DLB has a different progression from AD because frontal structures are involved earlier, with later involvement of temporoparietal brain structures.[127] Verbal memory is not as severely affected as in AD.[129] While 74% of people with autopsy-confirmed DLB had deficits in planning and organization, they show up in only 45% of people with AD.[130] Visuospatial processing deficits are present in most individuals with DLB,[57] and they show up earlier and are more pronounced than in AD.[131] Hallucinations typically occur early in the course of DLB,[5] are less common in early AD, but usually occur later in AD.[76] AD pathology frequently co-occurs in DLB, so the cerebrospinal fluid (CSF) testing for Aβ and tau protein that is often used to detect AD is not useful in differentiating AD and DLB.[49] PET or SPECT imaging can be used to detect reduced dopamine transporter uptake and distinguish AD from DLB.[49][132] Severe atrophy of the hippocampus is more typical of AD than DLB.[133] Before dementia develops (during the mild cognitive impairment phase), MRI scans show normal hippocampal volume. After dementia develops, MRI shows more atrophy among individuals with AD, and a slower reduction in volume over time among people with DLB than those with AD.[26] Compared to people with AD, FDG-PET brain scans in people with DLB often show a cingulate island sign.[26] In East Asia, particularly Japan,123I-MIBG is used in the differential diagnosis of DLB and AD, because reduced labeling of cardiac nerves is seen only in Lewy body disorders.[103][120] Other indicative and supportive biomarkers are useful in distinguishing DLB and AD (preservation of medial temporal lobe structures, reduced occipital activity, and slow-wave EEG activity).[24] #### Synucleinopathies[edit] Dementia with Lewy bodies and Parkinson's disease dementia are clinically similar after dementia occurs in Parkinson's disease.[134] Delusions in Parkinson's disease dementia are less common than in DLB,[135] and persons with Parkinson's disease are typically less caught up in their visual hallucinations than those with DLB.[76] There is a lower incidence of tremor at rest in DLB than in Parkinson's disease, and signs of parkinsonism in DLB are more symmetrical.[34] In multiple system atrophy, autonomic dysfunction appears earlier and is more severe,[31] and is accompanied by uncoordinated movements, while visual hallucinations and fluctuating cognition are less common than in DLB.[136] Urinary difficulty is one of the earliest symptoms with multiple system atrophy, and is often severe.[61] #### Frontotemporal dementias[edit] Corticobasal syndrome, corticobasal degeneration and progressive supranuclear palsy are frontotemporal dementias[137] with features of parkinsonism and impaired cognition. Similar to DLB, imaging may show reduced dopamine transporter uptake. Corticobasal syndrome and degeneration, and progressive supranuclear palsy, are usually distinguished from DLB by history and examination. Motor movements in corticobasal syndrome are asymmetrical. There are differences in posture, gaze and facial expressions in the most common variants of progressive supranuclear palsy, and falling backwards is more common relative to DLB. Visual hallucinations and fluctuating cognition are unusual in corticobasal degeneration and progressive supranuclear palsy.[137] ## Management[edit] Palliative care is offered to ameliorate symptoms, but there are no medications that can slow, stop, or improve the relentless progression of the disease.[138][139] No medications for DLB are approved by the United States Food and Drug Administration as of 2020,[140] although donepezil is licensed in Japan and the Philippines for the treatment of DLB.[141] As of 2020, there has been little study on the best management for non-motor symptoms such as sleep disorders and autonomic dysfunction; most information on management of autonomic dysfunction in DLB is based on studies of people with Parkinson's disease.[142] Management can be challenging because of the need to balance treatment of different symptoms: cognitive dysfunction, neuropsychiatric features, impairments related to the motor system, and other nonmotor symptoms.[143] Individuals with DLB have widely different symptoms that fluctuate over time, and treating one symptom can worsen another; suboptimal care can result from a lack or coordination among the physicians treating different symptoms.[142] A multidisciplinary approach—going beyond early and accurate diagnosis to include educating and supporting the caregivers—is favored.[9][144] ### Medication[edit] Antipsychotic sensitivity "The most fraught decision in the management of DLB relates to the use of antipsychotic medications ... DLB patients are particularly at risk of antipsychotic medication morbidity and mortality." —B.P. Boot (2015), Comprehensive treatment of dementia with Lewy bodies[58] Pharmacological management of DLB is complex because of adverse effects to medications[41] and the wide range of symptoms to be treated (cognitive, motor, neuropsychiatric, autonomic, and sleep).[9][17] Anticholinergic and dopaminergic agents can have adverse effects or result in psychosis in individuals with DLB,[9] and a medication that addresses one feature might worsen another.[145] For example, acetylcholinesterase inhibitors (AChEIs) for cognitive symptoms can lead to complications in dysautonomia features; treatment of movement symptoms with dopamine agonists may worsen neuropsychiatric symptoms; and treatment of hallucinations and psychosis with antipsychotics may worsen other symptoms or lead to a potentially fatal reaction.[143] Extreme caution is required in the use of antipsychotic medication in people with DLB because of their sensitivity to these agents.[146] Severe and life-threatening reactions occur in almost half of people with DLB,[10][57] and can be fatal after a single dose.[58] Antipsychotics with D2 dopamine receptor-blocking properties are used only with great caution.[56] According to Boot (2013), "electing not to use neuroleptics is often the best course of action".[147] People with Lewy body dementias who take neuroleptics are at risk for neuroleptic malignant syndrome, a life-threatening illness.[43] There is no evidence to support the use of antipsychotics to treat the Lewy body dementias,[10] and they carry the additional risk of stroke when used in the elderly with dementia.[77] Medications (including tricyclic antidepressants and treatments for urinary incontinence) with anticholinergic properties that cross the blood-brain barrier can cause memory loss.[148] The antihistamine medication diphenhydramine (Benadryl), sleep medications like zolpidem,[148] and benzodiazepines may worsen confusion[149] or neuropsychiatric symptoms.[150] Some general anesthetics may cause confusion or delirium upon waking in persons with Lewy body dementias, and may result in permanent decline.[2] #### Cognitive symptoms[edit] There is strong evidence for the use of AChEIs to treat cognitive problems; these medications include rivastigmine and donepezil.[3][6] Both are first-line treatments in the UK.[6] Even when the AChEIs do not lead to improvement in cognitive symptoms, people taking them may have less deterioration overall,[6] although there may be adverse gastrointestinal effects.[151] The use of these medications has demonstrated a reduced burden on caregivers, and improvement in activities of daily living for the individual with DLB.[6] The AChEIs are initiated carefully as they may aggravate autonomic dysfunction or sleep behaviors.[152] There is less evidence for the efficacy of memantine in DLB,[6] but it may be used alone or with an AChEI because of its low side effect profile.[9] Anticholinergic drugs are avoided because they worsen cognitive symptoms.[151] To improve daytime alertness, there is mixed evidence for the use of stimulants such as methylphenidate and dextroamphetamine; although worsening of neuropsychiatric symptoms is not common, they can increase the risk of psychosis.[153] Modafinil and armodafinil may be effective for daytime sleepiness.[154] #### Motor symptoms[edit] Motor symptoms in DLB appear to respond somewhat less to medications used to treat Parkinson's disease, like levodopa, and these medications can increase neuropsychiatric symptoms.[9][48] Almost one out of every three individuals with DLB develops psychotic symptoms from levadopa.[48] If such medications are needed for motor symptoms, cautious introduction with slow increases to the lowest possible dose may help avoid psychosis.[9] #### Neuropsychiatric symptoms[edit] Neuropsychiatric symptoms of DLB (aggression, anxiety, apathy, delusions, depression and hallucinations) do not always require treatment.[10] The first line of defense in decreasing visual hallucinations is to reduce the use of dopaminergic drugs, which can worsen hallucinations.[151] If new neuropsychiatric symptoms appear, the use of medications (such as anticholinergics, tricyclic antidepressants, benzodiazepines and opioids) that might be contributing to these symptoms is reviewed.[155] Among the AChEIs, rivastigmine, donepezil, and galantamine can help reduce neuropsychiatric symptoms,[10] and improve the frequency and severity of hallucinations in the less severe stages of DLB.[53] Although it has been shown effective in Parkinson's disease, there is limited evidence for the use of clozapine to treat visual hallucinations in DLB, and its use requires regular blood monitoring.[151] Quetiapine is relatively safe[9] and well tolerated for psychosis and agitation in DLB, but there is little evidence for its efficacy.[156] Apathy may be treated with AChEIs, and they may also reduce hallucinations, delusions, anxiety and agitation.[9] Most medications to treat anxiety and depression have not been adequately investigated for DLB.[10] Antidepressants may affect sleep and worsen RBD.[22][10][74] Mirtazapine and SSRIs can be used to treat depression, depending on how well they are tolerated, and guided by general advice for the use of antidepressants in dementia.[9] Antidepressants with anticholinergic properties may worsen hallucinations and delusions.[77] People with Capgras syndrome may not tolerate AChEIs.[56] #### Sleep disorders[edit] Injurious dream enactment behaviors are a treatment priority.[42] RBD may be treated with melatonin or clonazepam.[157] Sleep medications are carefully evaluated for each individual as they carry increased risk of falls, increased daytime sleepiness, and worsening cognition.[22] Melatonin may be more helpful in preventing injuries,[158] and it offers a safer alternative, because clonazepam can produce deteriorating cognition,[9] and worsen sleep apnea.[158] For some people, memantine is useful.[22] Modafinil may be used for hypersomnia, but no trials support its use in DLB.[77] Mirtazapine can be used for hypersomnia, but it can exacerbate RBD.[77] Antidepressants (SSRIs, SNRIs, tricyclics, and MAOIs), AChEIs, beta blockers, caffeine, and tramadol may worsen RBD.[158] #### Autonomic symptoms[edit] Decreasing the dosage of dopaminergic or atypical antipsychotic drugs may be needed with orthostatic hypotension, and high blood pressure drugs can sometimes be stopped.[77] When non-pharmacological treatments for orthostatic hypotension have been exhausted, fludrocortisone, droxidopa, or midodrine are options,[159] but these drugs have not been specifically studied for DLB as of 2020.[68] Delayed gastric emptying can be worsened by dopaminergic medications, and constipation can be worsened by opiates and anticholinergic medications.[68] Muscarinic antagonists used for urinary symptoms might worsen cognitive impairment in people with Lewy body dementias.[68] ### Other[edit] There is no high-quality evidence for non-pharmacological management of DLB,[9][68] but some interventions have been shown effective for addressing similar symptoms that occur in other dementias.[160] For example, organized activities, music therapy, physical activity and occupational therapy may help with psychosis or agitation, while exercise and gait training can help with motor symptoms.[160] Cognitive behavioral therapy can be tried for depression or hallucinations, although there is no evidence for its use in DLB.[161] Cues can be used to help with memory retrieval.[31] The first steps in managing sleep disorders are to evaluate the use of medications that impact sleep and provide education about sleep hygiene.[22] Frequency and severity of RBD may be lessened by treating sleep apnea, if it is present.[157] For autonomic dysfunction, several non-medication strategies may be helpful. Dietary changes include avoiding meals high in fat[68] and sugary foods, eating smaller and more frequent meals,[162] after-meal walks, and increasing fluids or dietary fiber to treat constipation.[68] Stool softeners and exercise also help with constipation.[68] Excess sweating can be helped by avoiding alcohol and spicy foods, and using cotton bedding and loose fitting clothing.[68] Physical exercise in a sitting or recumbent position, and exercise in a pool, can help maintain conditioning.[163] Compression stockings and elevating the head of the bed may also help, and increasing fluid intake or table salt can be tried to reduce orthostatic hypotension.[68] To lessen the risk of fractures in individuals at risk for falls, bone mineral density screening and testing of vitamin D levels are used,[164] and caregivers are educated on the importance of preventing falls.[165] Physiotherapy has been shown helpful for Parkinson's disease dementia, but as of 2020, there is no evidence to support physical therapy in people with DLB.[48] ### Caregiving[edit] Further information: Caring for people with dementia Teaching caregivers how to manage neuropsychiatric symptoms (such as agitation and psychosis) is recommended.[164] Because of the neuropsychiatric symptoms associated with DLB, the demands placed on caregivers are higher than in AD,[145] but education for caregivers has not been studied as thoroughly as in AD or Parkinson's disease.[9] Contributing factors to the caregiver burden in DLB are emotional fluctuations,[145] psychosis, aggression, agitation, and night-time behaviors such as parasomnias,[122] that lead to a loss of independence earlier than in AD.[166] Caregivers may experience depression and exhaustion, and they may need support from other people.[167] Other family members who are not present in the daily caregiving may not observe the fluctuating behaviors or recognize the stress on the caregiver, and conflict can result when family members are not supportive.[2] Caregiver education reduces not only distress for the caregiver, but symptoms for the individual with dementia.[160] Visual hallucinations associated with DLB create a particular burden on caregivers.[168] Educating caregivers on how to distract or change the subject when confronted with hallucinations is more effective than arguing over the reality of the hallucination.[169][170] Coping strategies may help and are worth trying, even though there is no evidence for their efficacy.[171] These strategies include having the person with DLB look away or look at something else, focus on or try to touch the hallucination, wait for it to go away on its own, and speak with others about the visualization.[172] Delusions and hallucinations may be reduced by increasing lighting in the evening, and making sure there is no light at night when the individual with DLB is sleeping.[169] With the increased risk of side effects from antipsychotics for people with DLB, educated caregivers are able to act as advocates for the person with DLB.[173] If evaluation or treatment in an emergency room is needed, the caregiver may be able to explain the risks associated with neuroleptic use for persons with DLB.[43] Caregiver training, watchful waiting, identifying sources of pain, and increasing social interaction can help minimize agitation.[75] Individuals with dementia may not be able to communicate that they are in pain, and pain is a common trigger of agitation.[174] Medical alert bracelets or notices about medication sensitivity are available and can save lives.[175] A home safety assessment can be done when there is risk of falling.[9] Handrails and shower chairs can help avoid falls.[176] Individuals and their caregivers can be counselled about the need to improve bedroom safety for RBD symptoms.[177] Sleep-related injuries from falling or jumping out of bed can be avoided by lowering the height of the bed,[22] placing a mattress next to the bed to soften the impact of a fall, and removing sharp objects from around the bed.[22] Sharp surfaces near the bed can be padded, bed alarm systems may help with sleepwalking, and bed partners may find it safer to sleep in another room.[177] According to St Louis and Boeve, firearms should be locked away, out of the bedroom.[177] Driving ability may be impaired early in DLB because of visual hallucinations, movement issues related to parkinsonism, and fluctuations in cognitive ability, and at some point it becomes unsafe for the person to drive.[178] Driving ability is assessed as part of management, and family members generally determine when driving privileges are removed.[178][176] ## Prognosis[edit] The prognosis for DLB has not been well studied; early studies had methodological limitations, such as small sample size and selection bias.[179] Relative to AD, DLB generally leads to higher disability, lower life expectancy and a reduced quality of life, with increased costs of care.[180] Depression, apathy, and visual hallucinations contribute to the reduced quality of life.[181] Decline may be more rapid when severe visuospatial deficits show up early in the course of the Lewy body dementias,[182] when the APOE gene is present, or when AD—or its biomarkers—is also present.[183] The severity of orthostatic hypotension also predicts a worse prognosis.[184] Compared to AD, which is better studied, memory is retained longer, while verbal fluency may be lost faster.[183] There are more neuropsychiatric symptoms in DLB than AD, and they may emerge earlier, so those with DLB may have a less favorable prognosis, with more rapid cognitive decline, more admissions to residential care, and a lower life expectancy.[185][179] An increased rate of hospitalization compared to AD is most commonly related to hallucinations and confusion, followed by falls and infection.[186] Life expectancy is difficult to predict, and limited study data are available.[167] Survival may be defined from the point of disease onset, or from the point of diagnosis.[187] A 2017 review found survival from disease onset between 5.5 and 7.7 years, survival from diagnosis between 1.9 and 6.3 years, and a shorter survival time after diagnosis than in AD. The difference in survival between AD and DLB could be because DLB is harder to diagnose, and may be diagnosed later in the course of the disease.[187] The US National Institute of Neurological Disorders and Stroke writes that people with DLB typically live 8 years following diagnosis, about the same as AD,[4] though some people with Lewy body dementias live for 20 years.[2] Shorter life expectancy is more likely when visual hallucinations, abnormal gait, and variable cognition are present early on.[167] In the late part of the disease, people may be unable to care for themselves.[18] Falls—caused by many factors including parkinsonism, dysautonomia, and frailness—increase morbidity and mortality.[48] Aspiration pneumonia, a complication of dysphagia that results from dysautonomia, commonly causes death among people with the Lewy body dementias.[71] Following pneumonia, cardiovascular disease and sepsis are common causes of death.[145] ## Epidemiology[edit] The Lewy body dementias are as a group the second most common form of neurodegenerative dementia after AD as of 2020.[142] DLB itself is one of the three most common types of dementia, along with AD and vascular dementia.[2][188][d] The diagnostic criteria for DLB before 2017 were highly specific, but not very sensitive,[189] so that more than half of cases were missed historically.[166] Dementia with Lewy bodies was under-recognized as of 2020,[102] and there is little data on its epidemiology.[134] The incidence and prevalence of DLB are not known accurately, but estimates are increasing with better recognition of the condition since 2017.[190] About 0.4% of those over the age 65 are affected with DLB,[8] and between 1 and 4 per 1,000 people develop the condition each year.[191][192] Symptoms usually appear between the ages of 50 and 80,[8] (median 76[3]) and it is not uncommon for it to be diagnosed before the age of 65.[134] DLB is thought to be slightly more common in men than women,[3] but a 2014 review challenged that view, and said that the gender distribution was unclear.[193] An estimated 10 to 15% of diagnosed dementias are Lewy body type, but estimates range as high as 23%[134] for those in clinical studies.[145] A French study found an incidence among persons 65 years and older almost four times higher than a US study (32 US vs 112 France per 100,000 person-years), but the US study may have excluded people with only mild or no parkinsonism, while the French study screened for parkinsonism.[134] Neither of the studies assessed systematically for RBD, so DLB may have been underdiagnosed in both studies.[134] A door-to-door study in Japan found a prevalence of 0.53% for persons 65 and older, and a Spanish study found similar results.[194] ## History[edit] Frederic Lewy (1885–1950) was the first to discover the abnormal protein deposits in the early 1900s.[195][196] In 1912, studying Parkinson's disease (paralysis agitans),[197] he described findings of these inclusions in the vagus nerve, the nucleus basalis of Meynert and other brain regions.[145][198] He published a book, The Study on Muscle Tone and Movement. Including Systematic Investigations on the Clinic, Physiology, Pathology, and Pathogenesis of Paralysis agitans, in 1923 and except for one brief paper a year later, never mentioned his findings again.[199] In 1961, Okazaki et al. published an account of diffuse Lewy-type inclusions associated with dementia in two autopsied cases.[195][200] Dementia with Lewy bodies was fully described in an autopsied case by Japanese psychiatrist and neuropathologist Kenji Kosaka in 1976.[201][202] Kosaka first proposed the term Lewy body disease four years later, based on 20 autopsied cases.[32][200] DLB was thought to be rare until it became easier to diagnose in the 1980s after the discovery of alpha-synuclein immunostaining that highlighted Lewy bodies in post mortem brains.[195] Kosaka et al. described thirty-four more cases in 1984, which were mentioned along with four UK cases by Gibb et al. in 1987 in the journal Brain, bringing attention of the Japanese work to the Western world.[203] A year later, Burkhardt et al. published the first general description of diffuse Lewy body disease.[204] With Japanese, UK, and US researchers finding in the 1990s that DLB was a common dementia, there were nonetheless no diagnostic guidelines, and each group was using different terminology.[205] The different groups of researchers began to realize that a collaborative approach was needed if research was to advance.[206] The DLB Consortium was established, and in 1996, the term dementia with Lewy bodies was agreed upon[80] and the first criteria for diagnosing DLB were elaborated.[32] Two 1997 discoveries highlighted the importance of Lewy body inclusions in neurodegenerative processes: a mutation in the SNCA gene that encodes the alpha-synuclein protein was found in kindreds with Parkinson's disease, and Lewy bodies and neurites were found to be immunoreactive for alpha-synuclein.[207] Thus, alpha-synuclein aggregation as the primary building block of the synucleinopathies was established.[207] Between 1995 and 2005, the DLB Consortium issued three Consensus Reports on DLB.[208] DLB was included in the fourth text revision of the DSM (DSM-IV-TR, published in 2000) under "Dementia due to other general medical conditions”. In the 2010s, the possibility of a genetic basis began to emerge.[81] The Fourth Consensus Report was issued in 2017, giving increased diagnostic weighting to RBD and 123I-MIBG myocardial scintigraphy.[105] ## Society and culture[edit] Main article: Lewy body dementia § Society and culture His widow said Robin Williams (shown in 2011) was diagnosed during autopsy as having diffuse Lewy bodies.[209][210][211] The British author and poet Mervyn Peake died in 1968 and was diagnosed posthumously as a probable case of DLB in a 2003 study published in JAMA Neurology.[212] Based on signs in his work and letters of progressive deterioration, fluctuating cognitive decline, deterioration in visuospatial function, declining attention span, and visual hallucinations and delusions, his may be the earliest known case where DLB was found to have been the likely cause of death.[212] At the time of his suicide on August 11, 2014, Robin Williams, the American actor and comedian, had been diagnosed with Parkinson's disease.[209] According to his widow, Williams had experienced depression, anxiety and increasing paranoia.[210] His widow said that his autopsy found diffuse Lewy body disease,[209][210][211] while the autopsy used the term diffuse Lewy body dementia.[213] Dennis Dickson, a spokesperson for the Lewy Body Dementia Association, clarified the distinction by stating that diffuse Lewy body dementia is more commonly called diffuse Lewy body disease and refers to the underlying disease process.[213] According to Dickson, "Lewy bodies are generally limited in distribution, but in DLB, the Lewy bodies are spread widely throughout the brain, as was the case with Robin Williams."[213] Ian G. McKeith, professor and researcher of Lewy body dementias, commented that Williams' symptoms and autopsy findings were explained by DLB.[214] ## Research directions[edit] The identification of prodromal biomarkers for DLB will enable treatments to begin sooner,[215] improve the ability to select subjects and measure efficacy in clinical trials,[216] and help families and clinicians plan for early interventions and awareness of potential adverse affects from the use of antipsychotics.[217] Criteria were proposed in 2020 to help researchers better recognize DLB in the pre-dementia phase.[20][218] Three syndromes of prodromal DLB have been proposed: 1) mild cognitive impairment with Lewy bodies (MCI-LB); 2) delirium-onset DLB; and 3) psychiatric-onset DLB.[20] The three early syndromes may overlap.[219] As of 2020, the DLB Diagnostic Study Group's position is that criteria for MCI-LB can be recommended, but that it remains difficult to distinguish delirium-onset and pschiatric-onset DLB without better biomarkers.[219] The diagnosis of DLB is made using the DLB Consortium criteria, but a 2017 study of skin samples from 18 people with DLB found that all of them had deposits of phosphorylated alpha-synuclein, while none of the controls did,[220] suggesting that skin samples are a potential biomarker.[221] Other potential biomarkers under investigation are quantitative electroencephalography, imaging examination of brain structures, and measures of CSF.[222] Cognitive training, deep brain stimulation and transcranial direct-current stimulation have been studied more in Parkinson's and Alzheimer's disease than they have in dementia with Lewy bodies, and all are potential therapies for DLB.[215] As of 2019, clinical trials for several drugs are underway. Trials for the antipsychotic pimavanserin for individuals with DLB are ongoing,[10] but it has risks of cardiac side effects and increased mortality.[29] The anticonvulsant zonisamide is approved in Japan for treating Parkinson's disease and is in clinical trials for treating parkinsonism symptoms in DLB.[29] Strategies for future intervention involve modifying the course of the disease using immunotherapy, gene therapy, and stem cell therapy, and reducing amyloid beta or alpha-synuclein accumulation. Therapies under study as of 2019 aim to reduce brain levels of alpha-synuclein (with the pharmaceuticals ambroxol, NPT200-11, and E2027) or to use immunotherapy to reduce widespread neuroinflammation resulting from alpha-synuclein deposits.[215][223] ## Notes[edit] 1. ^ a b Areas of the brain and functions affected:[18] * cerebral cortex – thought, perception and language; * limbic cortex – emotions and behavior; * hippocampus – memory; * midbrain and basal ganglia – movement; * brain stem – sleep, alertness, and autonomic dysfunction; * olfactory cortex – smell. Also affected are the hypothalamus, spinal cord and peripheral nervous system—autonomic dysfunction.[89] 2. ^ The European Federation of Neurological Societies—European Neurological Society and the British Association for Psychopharmacology also have diagnostic guidelines, but they were not developed specifically for DLB, hence the DLB Consortium guidelines are the most widely used and cited.[109] 3. ^ Questionnaires such as the REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ), the REM Sleep Behavior Questionnaires – Hong-Kong (RBD-HK), the Mayo Sleep Questionnaire (MSQ), the Innsbruck REM Sleep Behavior Disorder Inventory, and the REM Sleep Behavior Disorder Single-Question Screen are well-validated.[42] 4. ^ Kosaka (2017) writes: "Dementia with Lewy bodies (DLB) is now well known to be the second most frequent dementia following Alzheimer disease (AD). Of all types of dementia, AD is known to account for about 50%, DLB about 20% and vascular dementia (VD) about 15%. Thus, AD, DLB, and VD are now considered to be the three major dementias."[188] The NINDS (2020) says that Lewy body dementia "is one of the most common causes of dementia, after Alzheimer’s disease and vascular disease."[2] Hershey (2019) says, "DLB is the third most common of all the neurodegenerative diseases behind both Alzheimer's disease and Parkinson's disease".[3] ## References[edit] 1. ^ a b c d e f g h i j k l m n o p McKeith, Boeve & Dickson 2017, Table 1, p. 90. 2. ^ a b c d e f g h i j k l m n "Lewy body dementia: Hope through research". National Institute of Neurological Disorders and Stroke. US National Institutes of Health. January 10, 2020. Retrieved March 18, 2020. 3. ^ a b c d e f g Hershey & Coleman-Jackson 2019, p. 309. 4. ^ a b c d e f "Dementia with Lewy bodies information page". National Institute of Neurological Disorders and Stroke. March 27, 2019. Retrieved March 18, 2020. 5. ^ a b c d e f g h i j k Gomperts 2016, p. 437. 6. ^ a b c d e f Taylor, McKeith & Burn 2020, sec. "Cognitive impairment". 7. ^ Taylor, McKeith & Burn 2020, sec. "Sleep disturbances" (The "Nocturnal sleep disturbances" and "Excessive Daytime Sleepiness" sections were combined on final publication, so the courtesy online copy differs from the actual journal article). 8. ^ a b c d Levin et al. 2016, p. 62. 9. ^ a b c d e f g h i j k l m n o McKeith, Boeve & Dickson 2017, sec. "Clinical management", pp. 93–95. 10. ^ a b c d e f g h i Taylor, McKeith & Burn 2020, sec. "Neuropsychiatric symptoms". 11. ^ Boot 2015, sec. "Introduction". 12. ^ Weil et al. 2017, Abstract. 13. ^ Taylor, McKeith & Burn 2020, Abstract. 14. ^ Levin et al. 2016, p. 61. 15. ^ Goedert, Jakes & Spillantini 2017, p. S56. 16. ^ Armstrong 2019, p. 128. 17. ^ a b c Boot 2015, Abstract. 18. ^ a b c d e "What is Lewy body dementia?". National Institute on Aging. US National Institutes of Health. 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Classification D * ICD-11: 8A22/6D82 * ICD-10: G31.8 * ICD-9-CM: 331.82 * MeSH: D020961 * v * t * e Diseases of the nervous system, primarily CNS Inflammation Brain * Encephalitis * Viral encephalitis * Herpesviral encephalitis * Limbic encephalitis * Encephalitis lethargica * Cavernous sinus thrombosis * Brain abscess * Amoebic Brain and spinal cord * Encephalomyelitis * Acute disseminated * Meningitis * Meningoencephalitis Brain/ encephalopathy Degenerative Extrapyramidal and movement disorders * Basal ganglia disease * Parkinsonism * PD * Postencephalitic * NMS * PKAN * Tauopathy * PSP * Striatonigral degeneration * Hemiballismus * HD * OA * Dyskinesia * Dystonia * Status dystonicus * Spasmodic torticollis * Meige's * Blepharospasm * Athetosis * Chorea * Choreoathetosis * Myoclonus * Myoclonic epilepsy * Akathisia * Tremor * Essential tremor * Intention tremor * Restless legs * Stiff-person Dementia * Tauopathy * Alzheimer's * Early-onset * Primary progressive aphasia * Frontotemporal dementia/Frontotemporal lobar degeneration * Pick's * Dementia with Lewy bodies * Posterior cortical atrophy * Vascular dementia Mitochondrial disease * Leigh syndrome Demyelinating * Autoimmune * Inflammatory * Multiple sclerosis * For more detailed coverage, see Template:Demyelinating diseases of CNS Episodic/ paroxysmal Seizures and epilepsy * Focal * Generalised * Status epilepticus * For more detailed coverage, see Template:Epilepsy Headache * Migraine * Cluster * Tension * For more detailed coverage, see Template:Headache Cerebrovascular * TIA * Stroke * For more detailed coverage, see Template:Cerebrovascular diseases Other * Sleep disorders * For more detailed coverage, see Template:Sleep CSF * Intracranial hypertension * Hydrocephalus * Normal pressure hydrocephalus * Choroid plexus papilloma * Idiopathic intracranial hypertension * Cerebral edema * Intracranial hypotension Other * Brain herniation * Reye syndrome * Hepatic encephalopathy * Toxic encephalopathy * Hashimoto's encephalopathy Both/either Degenerative SA * Friedreich's ataxia * Ataxia–telangiectasia MND * UMN only: * Primary lateral sclerosis * Pseudobulbar palsy * Hereditary spastic paraplegia * LMN only: * Distal hereditary motor neuronopathies * Spinal muscular atrophies * SMA * SMAX1 * SMAX2 * DSMA1 * Congenital DSMA * Spinal muscular atrophy with lower extremity predominance (SMALED) * SMALED1 * SMALED2A * SMALED2B * SMA-PCH * SMA-PME * Progressive muscular atrophy * Progressive bulbar palsy * Fazio–Londe * Infantile progressive bulbar palsy * both: * Amyotrophic lateral sclerosis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Dementia with Lewy bodies	c0752347	28,521	wikipedia	https://en.wikipedia.org/wiki/Dementia_with_Lewy_bodies	2021-01-18T19:08:31	{"mesh": ["D020961"], "wikidata": ["Q101245788"]}
A number sign (#) is used with this entry because of evidence that mitochondrial complex I deficiency nuclear type 32 (MC1DN32) is caused by compound heterozygous mutation in the NDUFB8 gene (602140) on chromosome 10q24. For a discussion of genetic heterogeneity of mitochondrial complex I deficiency, see 252010. Clinical Features Piekutowska-Abramczuk et al. (2018) reported 2 unrelated children with mitochondrial complex I deficiency. One child presented at 3 months of age with respiratory failure, seizures, and increased serum and CSF lactate. He had hypotonia, failure to thrive, and severely delayed psychomotor development with limited contact with his environment. He also developed left ventricular cardiac hypertrophy. Brain imaging showed signal alterations in the midbrain, putamen, and thalamus, consistent with Leigh syndrome (see 256000) with later development of supratentorial and brainstem atrophy and cystic lesions. The patient was ventilator-dependent and fully dependent for all daily life activities. The other child was born at term and needed immediate resuscitation. He had poor growth, hypotonia, and delayed development. Laboratory studies showed increased serum and CSF lactate and lesions in the basal ganglia and internal capsule, consistent with Leigh syndrome. He died at age 15 months. Molecular Genetics In 2 unrelated children with mitochondrial complex I deficiency nuclear type 32 manifest as Leigh syndrome, Piekutowska-Abramczuk et al. (2018) identified compound heterozygous mutations in the NDUFB8 gene (602140.0001-602140.0004). The mutations, which were found by whole-exome or targeted exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. INHERITANCE \- Autosomal recessive GROWTH Other \- Failure to thrive CARDIOVASCULAR Heart \- Cardiac hypertrophy (1 of 2 patients) RESPIRATORY \- Respiratory insufficiency MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Delayed or absent psychomotor development \- Poor interaction with environment \- Seizures \- White matter abnormalities consistent with Leigh syndrome seen on brain imaging \- Supratentorial and brainstem atrophy METABOLIC FEATURES \- Metabolic acidosis LABORATORY ABNORMALITIES \- Increased serum lactate \- Increased CSF lactate \- Mitochondrial complex I deficiency in various tissues MISCELLANEOUS \- Onset in infancy \- Early death may occur \- Two unrelated patients have been reported (last curated January 2019) MOLECULAR BASIS \- Caused by mutation in the NADH-ubiquinone oxidoreductase subunit B8 gene (NDUFB8, 602140.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 32	None	28,522	omim	https://www.omim.org/entry/618252	2019-09-22T15:42:48	{"omim": ["618252"], "orphanet": ["70474"], "synonyms": ["Cardiomyopathy with hypotonia due to cytochrome C oxidase deficiency", "Cardiomyopathy with myopathy due to COX deficiency", "Leigh disease with myopathy"]}
Sheldon-Hall syndrome, also known as distal arthrogryposis type 2B, is a disorder characterized by joint deformities (contractures) that restrict movement in the hands and feet. The term "arthrogryposis" comes from the Greek words for joint (arthro-) and crooked or hooked (gryposis). "Distal" refers to areas of the body away from the center. The characteristic features of this condition include permanently bent fingers and toes (camptodactyly), overlapping fingers, and a hand deformity called ulnar deviation in which all of the fingers are angled outward toward the fifth (pinky) finger. Inward- and upward-turning feet (a condition called clubfoot) is also commonly seen in Sheldon-Hall syndrome. The specific hand and foot abnormalities vary among affected individuals; the abnormalities are present at birth and generally do not get worse over time. People with Sheldon-Hall syndrome also usually have distinctive facial features, which include a triangular face; outside corners of the eyes that point downward (down-slanting palpebral fissures); deep folds in the skin between the nose and lips (nasolabial folds); and a small mouth with a high, arched roof of the mouth (palate). Other features that may occur in Sheldon-Hall syndrome include extra folds of skin on the neck (webbed neck) and short stature. Sheldon-Hall syndrome does not usually affect other parts of the body, and intelligence and life expectancy are normal in this disorder. ## Frequency The prevalence of Sheldon-Hall syndrome is unknown; however, it is thought to be the most common type of distal arthrogryposis. About 100 affected individuals have been described in the medical literature. ## Causes Sheldon-Hall syndrome can be caused by mutations in the MYH3, TNNI2, TNNT3, or TPM2 gene. These genes provide instructions for making proteins that are involved in muscle tensing (contraction). Muscle contraction occurs when thick filaments made of proteins called myosins slide past thin filaments made of proteins called actins. The MYH3 gene provides instructions for making a myosin protein that is normally active only before birth and is important for early development of the muscles. The process of muscle contraction is controlled (regulated) by other proteins called troponins and tropomyosins, which affect the interaction of myosin and actin. Certain troponin proteins are produced from the TNNI2 and TNNT3 genes. The TPM2 gene provides instructions for making a tropomyosin protein. Mutations in the MYH3, TNNI2, TNNT3, or TPM2 gene likely interfere with normal muscle development or prevent muscle contractions from being properly controlled, resulting in the contractures and other muscle and skeletal abnormalities associated with Sheldon-Hall syndrome. It is unknown why the contractures mainly affect the hands and feet or how these gene mutations are related to other features of this disorder. ### Learn more about the genes associated with Sheldon-Hall syndrome * MYH3 * TNNI2 * TNNT3 * TPM2 ## Inheritance Pattern This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In about 50 percent of cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Sheldon-Hall syndrome	c1834523	28,523	medlineplus	https://medlineplus.gov/genetics/condition/sheldon-hall-syndrome/	2021-01-27T08:25:47	{"gard": ["9909"], "mesh": ["C538400"], "omim": ["601680"], "synonyms": []}
Probenecid and pyrazinamide are the drugs most widely used in the evaluation of the renal handling of urate. By application of these drugs, three types of tubular defects responsible for renal hypouricemia have been identified (De Vries and Sperling, 1979). They include presecretory, postsecretory, and combined urate reabsorption in the kidney (see 220150). A fourth type of renal hypouricemia was described by Shichiri et al. (1982), Dumont and Decaux (1983), and Sanz et al. (1983). In this type of hypouricemia, responses of renal urate clearance to probenecid or pyrazinamide are normal, sometimes even exaggerated, and the hypouricemia appears to be due to tubular hypersecretion. Nakajima et al. (1987) described the familial occurrence of this form. Two brothers had hypouricemia and their mother had serum urate levels in the low normal range. Data were not provided on the father. It is noteworthy that the proband was a 36-year-old carpenter with eunuchoidism and a 48,XXYY karyotype. His brother and mother had normal karyotypes. GU \- Renal hypouricemia Lab \- Renal tubular urate hypersecretion Inheritance \- X-linked ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	HYPOURICEMIA, FAMILIAL RENAL, DUE TO TUBULAR HYPERSECRETION	c1843972	28,524	omim	https://www.omim.org/entry/307830	2019-09-22T16:18:09	{"mesh": ["C564405"], "omim": ["307830", "220150"], "orphanet": ["94088"], "synonyms": []}
Nail–patella syndrome Other namesNPS Nail of a patient with nail–patella syndrome SpecialtyMedical genetics Nail–patella syndrome is a genetic disorder that results in small, poorly developed nails and kneecaps, but can also affect many other areas of the body, such as the elbows, chest, and hips. The name "nail–patella" can be very misleading because the syndrome often affects many other areas of the body, including even the production of certain proteins.[1]:666 Those affected by NPS may have one or more affected areas of the body, and its severity varies depending on the individual. It is also referred to as iliac horn syndrome, hereditary onychoosteodysplasia (HOOD syndrome), Fong disease or Turner–Kieser syndrome.[2] Diagnosis of NPS can be made at birth, but is common for it to remain undiagnosed for several generations. While there is no cure available for NPS, treatment is available and recommended. ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Diagnosis * 4 Treatment * 5 See also * 6 References * 7 External links ## Signs and symptoms[edit] The skeletal structures of individuals who have this disorder may have pronounced deformities. As reported by several medical doctors, the following features are commonly found in people who suffer from nail–patella syndrome:[3] Bones and joints AP radiograph showing a hypoplastic patella in NPS AP radiograph of the right iliac crest showing a bony exostosis or posterior iliac horn, which is pathognomonic of NPS * Patellar involvement is present in approximately 90% of patients; however, patellar aplasia occurs in only 20%. * In instances in which the patellae are smaller or luxated, the knees may be unstable. * The elbows may have limited motion (e.g., limited pronation, supination, extension). * Subluxation of the radial head may occur. * Arthrodysplasia of the elbows is reported in approximately 90% of patients. * General hyperextension of the joints can be present. * Exostoses arising from the posterior aspect of the iliac bones ("iliac horns") are present in as many as 80% of patients; this finding is considered pathognomonic for the syndrome. * Other reported bone changes include scoliosis, scapular hypoplasia, and the presence of cervical ribs. * An elbow of a man who suffers from nail–patella syndrome (NPS) * This is a view from a different angle of the same man's other elbow Kidney issues may arise such as deposition of protein in the urine and nephritis. Proteinuria is usually the first sign of kidney involvement and either rapidly or years after suffering from asymptomatic deposition of protein in the urine, kidney failure occurs in around 5% of NPS patients. Hypothyroidism, irritable bowel syndrome, attention deficit hyperactivity disorder (ADHD), and thin tooth enamel are associated with NPS, but whether these are related or simply coincidences are unclear.[4] ## Genetics[edit] Nail–patella syndrome is inherited in an autosomal dominant pattern. The Nail–patella syndrome is inherited via autosomal dominancy linked to aberrancy on human chromosome 9's q arm (the longer arm), 9q34. This autosomal dominancy means that only a single copy, instead of both, is sufficient for the disorder to be expressed in the offspring, meaning the chance of getting the disorder from an affected heterozygous parent is 50%. The frequency of the occurrence is 1/50,000. The disorder is linked to the ABO blood group locus.[citation needed] It is associated with random mutations in the LMX1B gene. Studies have been conducted and 83 mutations of this gene have been identified.[5][6][7] ## Diagnosis[edit] The hallmark features of this syndrome are poorly developed fingernails, toenails, and patellae (kneecaps). Sometimes, this disease causes the affected person to have either no thumbnails or a small piece of a thumbnail on the edge of the thumb. The lack of development, or complete absence of fingernails results from the loss of function mutations in the LMX1B gene. This mutation may cause a reduction in dorsalising signals, which then results in the failure to normally develop dorsal specific structures such as nails and patellae.[8] Other common abnormalities include elbow deformities, abnormally shaped pelvic (hip) bones, and kidney disease.[citation needed] ## Treatment[edit] Treatment for NPS varies depending on the symptoms observed. * Perform screening for kidney disease and glaucoma, surgery, intensive physiotherapy, or genetic counseling.[5] * ACE inhibitors are taken to treat proteinuria and hypertension in NPS patients. * Dialysis and kidney transplant. * Physical therapy, bracing and analgesics for joint pain. * Other surgery treatments such as patella realignment, joint replacement, and the cutting away of the head of radius. ## See also[edit] * List of cutaneous conditions * List of radiographic findings associated with cutaneous conditions ## References[edit] 1. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0. 2. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. Page 786-7. ISBN 0-7216-2921-0. 3. ^ Choczaj-Kukula, A., & Janniger, C. K. (2009). Nail–patella syndrome. In emedicine: WebMD. Retrieved October 11, 2009, from WebMD database. 4. ^ Buatti Chris (August 2007). "Nail-Patella Syndrome". Consultant 360. 47 (8). 5. ^ a b Sweeney E, Fryer A (March 2003). "Nail patella syndrome: a review of the phenotype aided by developmental biology". Journal of Medical Genetics. 40 (3): 153–162. doi:10.1136/jmg.40.3.153. PMC 1735400. PMID 12624132. 6. ^ Towers AL, Clay CA, Sereika SM, McIntosh I, Greenspan SL (April 2005). "Skeletal integrity in patients with nail patella syndrome". J. Clin. Endocrinol. Metab. 90 (4): 1961–5. doi:10.1210/jc.2004-0997. PMID 15623820. 7. ^ Romero P.; Sanhueza F.; Lopez P.; Reyes L.; Herrera L. (2011). "c.194 A>C (Q65P) mutation in the LMX1B gene in patients with nail-patella syndrome associated with glaucoma". Molecular Vision. 17: 1929–39. PMC 3154131. PMID 21850167. 8. ^ Wright M J (September 2000). "Achondroplasia and nail-patella syndrome: the compound phenotype". Journal of Medical Genetics. 37 (9): 25e–25. doi:10.1136/jmg.37.9.e25. PMC 1734684. PMID 10978372. ## External links[edit] * GeneReview/NCBI/NIH/UW entry on nail–patella syndrome Classification D * ICD-10: Q87.2 (ILDS Q87.230) * ICD-9-CM: 756.89 * OMIM: 161200 * MeSH: D009261 * DiseasesDB: 8773 * SNOMED CT: 22199006 External resources * eMedicine: ped/1546 derm/813 * Orphanet: 2614 * v * t * e Congenital abnormality syndromes Craniofacial * Acrocephalosyndactylia * Apert syndrome * Carpenter syndrome * Pfeiffer syndrome * Saethre–Chotzen syndrome * Sakati–Nyhan–Tisdale syndrome * Bonnet–Dechaume–Blanc syndrome * Other * Baller–Gerold syndrome * Cyclopia * Goldenhar syndrome * Möbius syndrome Short stature * 1q21.1 deletion syndrome * Aarskog–Scott syndrome * Cockayne syndrome * Cornelia de Lange syndrome * Dubowitz syndrome * Noonan syndrome * Robinow syndrome * Silver–Russell syndrome * Seckel syndrome * Smith–Lemli–Opitz syndrome * Snyder–Robinson syndrome * Turner syndrome Limbs * Adducted thumb syndrome * Holt–Oram syndrome * Klippel–Trénaunay–Weber syndrome * Nail–patella syndrome * Rubinstein–Taybi syndrome * Gastrulation/mesoderm: * Caudal regression syndrome * Ectromelia * Sirenomelia * VACTERL association Overgrowth syndromes * Beckwith–Wiedemann syndrome * Proteus syndrome * Perlman syndrome * Sotos syndrome * Weaver syndrome * Klippel–Trénaunay–Weber syndrome * Benign symmetric lipomatosis * Bannayan–Riley–Ruvalcaba syndrome * Neurofibromatosis type I Laurence–Moon–Bardet–Biedl * Bardet–Biedl syndrome * Laurence–Moon syndrome Combined/other, known locus * 2 (Feingold syndrome) * 3 (Zimmermann–Laband syndrome) * 4/13 (Fraser syndrome) * 8 (Branchio-oto-renal syndrome, CHARGE syndrome) * 12 (Keutel syndrome, Timothy syndrome) * 15 (Marfan syndrome) * 19 (Donohue syndrome) * Multiple * Fryns syndrome * v * t * e Genetic disorders relating to deficiencies of transcription factor or coregulators (1) Basic domains 1.2 * Feingold syndrome * Saethre–Chotzen syndrome 1.3 * Tietz syndrome (2) Zinc finger DNA-binding domains 2.1 * (Intracellular receptor): Thyroid hormone resistance * Androgen insensitivity syndrome * PAIS * MAIS * CAIS * Kennedy's disease * PHA1AD pseudohypoaldosteronism * Estrogen insensitivity syndrome * X-linked adrenal hypoplasia congenita * MODY 1 * Familial partial lipodystrophy 3 * SF1 XY gonadal dysgenesis 2.2 * Barakat syndrome * Tricho–rhino–phalangeal syndrome 2.3 * Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome * Denys–Drash syndrome * Duane-radial ray syndrome * MODY 7 * MRX 89 * Townes–Brocks syndrome * Acrocallosal syndrome * Myotonic dystrophy 2 2.5 * Autoimmune polyendocrine syndrome type 1 (3) Helix-turn-helix domains 3.1 * ARX * Ohtahara syndrome * Lissencephaly X2 * MNX1 * Currarino syndrome * HOXD13 * SPD1 synpolydactyly * PDX1 * MODY 4 * LMX1B * Nail–patella syndrome * MSX1 * Tooth and nail syndrome * OFC5 * PITX2 * Axenfeld syndrome 1 * POU4F3 * DFNA15 * POU3F4 * DFNX2 * ZEB1 * Posterior polymorphous corneal dystrophy * Fuchs' dystrophy 3 * ZEB2 * Mowat–Wilson syndrome 3.2 * PAX2 * Papillorenal syndrome * PAX3 * Waardenburg syndrome 1&3 * PAX4 * MODY 9 * PAX6 * Gillespie syndrome * Coloboma of optic nerve * PAX8 * Congenital hypothyroidism 2 * PAX9 * STHAG3 3.3 * FOXC1 * Axenfeld syndrome 3 * Iridogoniodysgenesis, dominant type * FOXC2 * Lymphedema–distichiasis syndrome * FOXE1 * Bamforth–Lazarus syndrome * FOXE3 * Anterior segment mesenchymal dysgenesis * FOXF1 * ACD/MPV * FOXI1 * Enlarged vestibular aqueduct * FOXL2 * Premature ovarian failure 3 * FOXP3 * IPEX 3.5 * IRF6 * Van der Woude syndrome * Popliteal pterygium syndrome (4) β-Scaffold factors with minor groove contacts 4.2 * Hyperimmunoglobulin E syndrome 4.3 * Holt–Oram syndrome * Li–Fraumeni syndrome * Ulnar–mammary syndrome 4.7 * Campomelic dysplasia * MODY 3 * MODY 5 * SF1 * SRY XY gonadal dysgenesis * Premature ovarian failure 7 * SOX10 * Waardenburg syndrome 4c * Yemenite deaf-blind hypopigmentation syndrome 4.11 * Cleidocranial dysostosis (0) Other transcription factors 0.6 * Kabuki syndrome Ungrouped * TCF4 * Pitt–Hopkins syndrome * ZFP57 * TNDM1 * TP63 * Rapp–Hodgkin syndrome/Hay–Wells syndrome/Ectrodactyly–ectodermal dysplasia–cleft syndrome 3/Limb–mammary syndrome/OFC8 Transcription coregulators Coactivator: * CREBBP * Rubinstein–Taybi syndrome Corepressor: * HR (Atrichia with papular lesions) [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Nail–patella syndrome	c0027341	28,525	wikipedia	https://en.wikipedia.org/wiki/Nail%E2%80%93patella_syndrome	2021-01-18T19:07:21	{"gard": ["7160"], "mesh": ["D009261"], "umls": ["C0027341"], "icd-9": ["756.89"], "orphanet": ["2614"], "wikidata": ["Q2035109"]}
A number sign (#) is used with this entry because pachyonychia congenita-1 (PC1) is caused by heterozygous mutation in the keratin-16 gene (KRT16; 148067) on chromosome 17q21. Description Pachyonychia congenita (PC) is an autosomal dominant genodermatosis with the main clinical features of hypertrophic nail dystrophy, painful and highly debilitating plantar keratoderma, oral leukokeratosis, and a variety of epidermal cysts. Although the condition had previously been subdivided clinically into Jadassohn-Lewandowsky PC type 1 and Jackson-Lawler PC type 2, patients with PC were later found to have a mixed constellation of both types, leading to a classification of PC based on genotype (summary by Sybert, 2010; Eliason et al., 2012; McLean et al., 2011). ### Historical Classification of Pachyonychia Congenita Gorlin et al. (1976) suggested that 2 distinct syndromes are subsumed under the designation pachyonychia congenita. PC type 1, the Jadassohn-Lewandowsky type, shows oral leukokeratosis. PC type 2, the Jackson-Lawler type, has natal teeth and epidermoid cysts (cylindromas), but no oral leukoplakia. Corneal dystrophy may be a feature exclusively of the Jackson-Lawler type. Smith et al. (1998) stated that PC type 2, in contrast to PC type 1, has minimal oral involvement and milder keratoderma, and multiple steatocystomas (184500) is a major clinical feature. Steatocystoma, also known as eruptive vellus cyst, is a cystic hamartoma lined by sebaceous ductal epithelium. On the basis of a study of 13 patients with PC type 1 or type 2, Terrinoni et al. (2001) concluded that the presence of pilosebaceous cysts following puberty is the best indicator of PC type 2; prepubescent patients are more difficult to classify due to the lack of cysts. Natal teeth are indicative of PC type 2, although their absence does not preclude the PC type 2 diagnosis. ### Genetic Heterogeneity of Pachyonychia Congenita See pachyonychia congenita-2 (PC2; 167210), caused by mutation in the KRT17 gene (148069) on chromosome 17; PC3 (615726), caused by mutation in the KRT6A gene (148041) on chromosome 2; and PC4 (615728), caused by mutation or in the KRT6B gene (148042) on chromosome 12. See 260130 for a possible autosomal recessive form of pachyonychia congenita. Nomenclature The form of PC caused by mutation in the KRT16 gene, here designated PC1, has also been designated PC-16 (Eliason et al., 2012) and PC-K16 (Shah et al., 2014). Clinical Features Pachyonychia congenita is characterized by oral leukokeratosis, onychogryposis, hyperkeratosis of the palms and soles, follicular keratosis, especially of the knees and elbows, and hyperhidrosis of the hands and feet. Occasionally dystrophic changes are also observed in the hair or cornea (Witkop and Gorlin, 1961). Laryngeal changes requiring tracheostomy for respiratory distress during childhood were reported by Stieglitz and Centerwall (1983) in father and son. Feinstein et al. (1988) classified 168 reported cases into 4 types, of which type IV, present in 7.2% of the cases, had laryngeal lesions, hoarseness, mental retardation, hair anomalies, and alopecia. Leachman et al. (2005) analyzed clinical, pathologic, and genetic data from the literature in 2 research registries. They found that more than 97% of PC cases exhibited fingernail and toenail thickening, and painful plantar keratoderma. Prospective evaluation of 57 PC patients from 41 families revealed variable clinical findings: hyperhidrosis (79%), oral leukokeratosis (75%), follicular keratosis (65%), palmar keratoderma (60%), cutaneous cysts (35%), hoarseness or laryngeal involvement (16%), coarse or twisted hair (26%), early primary tooth loss (14%), and presence of natal or prenatal teeth (2%). Stratification of these data by keratin mutation confirmed the increased incidence of cyst formation and natal teeth among PC2 patients, although cysts were more commonly seen in PC1 patients than had previously been reported (25-33%). Previously unreported clinical features of PC included development of painful oral and nipple lesions during breastfeeding, copious production of waxy material in ears, and inability to walk without an ambulatory aid (50%). ### Pachyonychia Congenita, Late-Onset Pachyonychia congenita with late onset of symptoms has been described by several authors (Paller et al., 1991; Iraci et al., 1993; Lucker and Steijlen, 1995; Mouaci-Midoun et al., 1996; Hannaford and Stapleton, 2000) and has been referred to as pachyonychia congenita tarda. Paller et al. (1991) described a late-onset form in which typical subungual hyperkeratoses began during the teenage years. Leukokeratosis and keratoderma of the palms and soles were associated. The family history of 3 of the 5 patients was consistent with autosomal dominant inheritance. Connors et al. (2001) described a young girl with clinical features of pachyonychia congenita type 1 in whom the typical skin and nail changes were not noted until the age of 6 years. Direct sequencing of the KRT16 gene revealed a novel lys354 to asn mutation (K354N; 148067.0008) in the central 2B domain of the KRT16 polypeptide. Mutations in this region of KRT16 had not been described, but had been described in homologous regions of KRT14 (148066) in the milder Koebner (131900) and Weber-Cockayne (131800) variants of epidermolysis simplex. It was unclear whether the position of the mutation was sufficient to explain the late-onset phenotype. Inheritance Pachyonychia congenita is inherited as an autosomal dominant trait (Gorlin et al., 1976). Murray (1921) found 7 affected in 3 generations. Kumer and Loos (1935) found 24 affected in 5 generations. McKusick (1971) observed an apparent new mutation with transmission from father to son in a Jewish family. Diagnosis ### Prenatal Diagnosis Using a genomic PCR system, Smith et al. (1999) carried out the first prenatal diagnosis of Jadassohn-Lewandowsky syndrome using CVS material, correctly predicting a normal fetus. Molecular Genetics In a sporadic case of pachyonychia congenita-1, described as the Jadassohn-Lewandowsky type, McLean et al. (1995) identified heterozygosity for a missense mutation (L132P; 148067.0001) in the helix initiation motif of KRT16. In affected members of a 5-generation Dutch family with the Jadassohn-Lewandowsky type of PC, Smith et al. (1999) identified heterozygosity for a missense mutation (R127P; 148067.0005) in the KRT16 gene. In a sporadic case of pachyonychia congenita-1, they identified heterozygosity for a 3-bp deletion in KRT16 (148067.0004). Smith et al. (2005) identified keratin mutations in 30 probands from the International Pachyonychia Congenita Research Registry, including 8 patients with mutations in the KRT16 gene (see, e.g., 148067.0001-148067.0003 and 148067.0012). Smith et al. (2005) noted that the probands from 2 families with the same mutation, N125S (148067.0003), had different phenotypes: 1 proband, who had complete lack of thickening and only minor splinter hemorrhages of the nails, was given a diagnosis of FNEPPK (613000), whereas the other proband had typical hypertrophic dystrophy involving 17 of 20 nails. The authors suggested that in keratin disorders, a combination of factors, genetic and environmental, might be involved in determining the overall clinical phenotype. In a 36-year-old Chinese woman with severe hypertrophic dystrophy of the toenails and diffuse painful plantar keratoderma, with subtle focal palmar hyperkeratoses and normal nails of the hands, Du et al. (2012) identified heterozygosity for a KRT16 missense mutation (N125G; 148067.0013). Her 5-year-old daughter, who had only focal plantar hyperkeratosis at pressure points, without nail or hand involvement, was also heterozygous for the mutation. Both patients reported hyperhidrosis of the hands and feet. The mutation was not found in unaffected family members or in 100 controls. INHERITANCE \- Autosomal dominant HEAD & NECK Mouth \- Oral leukokeratosis SKIN, NAILS, & HAIR Skin \- Palmoplantar hyperkeratosis \- Follicular hyperkeratosis Nails \- Onychogryposis MISCELLANEOUS \- Genetic heterogeneity MOLECULAR BASIS \- Caused by mutation in the keratin 16 gene (KRT16, 148067.0001 ) \- Caused by mutation in the keratin 6A gene (KRT6A, 148041.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	PACHYONYCHIA CONGENITA 1	c0265334	28,526	omim	https://www.omim.org/entry/167200	2019-09-22T16:36:48	{"mesh": ["D053549"], "omim": ["167200"], "orphanet": ["2309"], "synonyms": ["Alternative titles", "PACHYONYCHIA CONGENITA, JADASSOHN-LEWANDOWSKY TYPE, FORMERLY", "JADASSOHN-LEWANDOWSKY SYNDROME, FORMERLY"], "genereviews": ["NBK1280"]}
Neck mass SpecialtyENT surgery A neck mass or neck lump is an ambiguous mass found in the neck area. There are many different possible causes,[1] including congenital conditions like branchial anomalies and thyroglossal duct cysts.[2] ## Contents * 1 Workup * 2 See also * 3 References * 4 External links ## Workup[edit] Workup of a neck mass includes a medical history and a physical examination, where important characteristics are location, size, shape, consistency, tenderness, mobility, and color.[3] When this is not conclusive, further workup includes: * Blood tests * Medical imaging: Contrast CT is generally the initial study of choice for adults.[3] Medical ultrasound of the neck is useful in children because it avoids the radiation dose of CT.[3] In some cases, fine needle aspiration may assist in the diagnosis. ## See also[edit] * Cervical lymphadenopathy ## References[edit] 1. ^ "Neck Mass: Approach to the Patient With Nasal and Pharyngeal Symptoms: Merck Manual Professional". 2. ^ Schwetschenau E, Kelley DJ (September 2002). "The adult neck mass". Am Fam Physician. 66 (5): 831–8. PMID 12322776. 3. ^ a b c Daniel G Deschler, Joseph Zenga. "Evaluation of a neck mass in adults". UpToDate. This topic last updated: Dec 04, 2017. ## External links[edit] Classification D * ICD-10: R22.1 * ICD-9-CM: 784.2 * v * t * e Symptoms and signs relating to skin and subcutaneous tissue Disturbances of skin sensation * Hypoesthesia * Paresthesia * Formication * Hyperesthesia * Hypoalgesia * Hyperalgesia Circulation * Cyanosis * Pallor * Livedo * Livedo reticularis * Flushing * Petechia * Blanching Edema * Peripheral edema * Anasarca Other * Rash * Desquamation * Induration * Diaphoresis * Mass * Neck mass Skin * Asboe-Hansen sign * Auspitz's sign * Borsari's sign * Braverman's sign * Crowe sign * Dennie–Morgan fold * Darier's sign * Fitzpatrick's sign * Florid cutaneous papillomatosis * Gottron's sign * Hutchinson's sign * Janeway lesion * Kerr's sign * Koebner's phenomenon * Koplik's spots * Leser-Trelat sign * Nikolsky's sign * Pastia's sign * Russell's sign * Wickham striae * Wolf's isotopic response * Munro's microabscess Nails * Aldrich-Mees' lines * Beau's lines * Muehrcke's lines * Terry's nails 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Neck mass	c0149736	28,527	wikipedia	https://en.wikipedia.org/wiki/Neck_mass	2021-01-18T18:47:09	{"wikidata": ["Q6985524"]}
Hartsfield syndrome is a rare condition characterized by holoprosencephaly, which is an abnormality of brain development, and a malformation of the hands and feet called ectrodactyly. During early development before birth, the brain normally divides into two halves, the right and left hemispheres. Holoprosencephaly occurs when the brain fails to divide properly. In the most severe forms of holoprosencephaly, the brain does not divide at all. These affected individuals have one central eye (cyclopia) and a tubular nasal structure (proboscis) located above the eye. Most babies with severe holoprosencephaly die before birth or soon after. In less severe cases of holoprosencephaly, the brain is partially divided. The life expectancy of these affected individuals depends on the severity of signs and symptoms. People with Hartsfield syndrome often have other brain abnormalities associated with holoprosencephaly. Affected individuals may have a malfunctioning pituitary, which is a gland located at the base of the brain that produces several hormones. Because pituitary dysfunction leads to the partial or complete absence of these hormones, it can cause a variety of disorders. These include diabetes insipidus, which disrupts the balance between fluid intake and urine excretion; a shortage (deficiency) of growth hormone, leading to slow or delayed growth; and hypogonadotropic hypogonadism, which affects the production of hormones that direct sexual development. Dysfunction in other parts of the brain can cause seizures, feeding difficulties, and problems regulating body temperature and sleep patterns. People with Hartsfield syndrome have delayed development that ranges from mild to severe. The other hallmark feature of Hartsfield syndrome is ectrodactyly. Ectrodactyly is a deep split in the hands, feet, or both, with missing fingers or toes and partial fusion of the remaining digits. It can affect the hands and feet on one or both sides. Other features that have been described in people with Hartsfield syndrome include premature fusion of certain bones of the skull (craniosynostosis), heart defects, abnormalities of the bones of the spine (vertebrae), and abnormal genitalia. Some affected individuals have distinctive facial features, including eyes that are widely spaced (hypertelorism) or closely spaced (hypotelorism), ears that are abnormally small or unusually shaped, and a split in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate). ## Frequency Hartsfield syndrome appears to be a rare disorder. Fewer than 20 cases have been reported in the medical literature. For unknown reasons, most of the people who have been diagnosed with this disorder are male. ## Causes Hartsfield syndrome is caused by mutations in the FGFR1 gene, which provides instructions for making a protein called fibroblast growth factor receptor 1 (FGFR1). This receptor interacts with proteins called fibroblast growth factors (FGFs) to trigger signaling within cells. Signaling via the FGFR1 protein is involved in many critical processes, such as cell division and the regulation of cell growth and maturation. This signaling is important for the normal development and growth of several parts of the body, including the brain, bones of the head and face (craniofacial bones), and bones in the hands and feet. The FGFR1 gene mutations that cause Hartsfield syndrome severely disrupt the function of the FGFR1 protein, including its ability to bind to FGFs. As a result, the receptor is unable to transmit signals properly, which impairs many aspects of normal development. It is unclear how these changes lead specifically to holoprosencephaly, ectrodactyly, and the other features of Hartsfield syndrome. Some people with Hartsfield syndrome do not have an identified mutation in the FGFR1 gene. In these cases, the cause of the condition is unknown. Researchers are looking for other genetic changes that may also be associated with this disorder. ### Learn more about the gene associated with Hartsfield syndrome * FGFR1 ## Inheritance Pattern Hartsfield syndrome can have either an autosomal dominant or autosomal recessive pattern of inheritance. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. In these cases, the condition usually results from a new (de novo) mutation in the FGFR1 gene that occurs during the formation of reproductive cells (eggs or sperm) or in early embryonic development. Most of these affected individuals have no history of the disorder in their family. However, in a small number of cases, people with Hartsfield syndrome have inherited the altered gene from an unaffected parent who has an FGFR1 gene mutation only in the sperm or egg cells. This phenomenon is called germline mosaicism. Less commonly, Hartsfield syndrome is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Hartsfield syndrome	c1845146	28,528	medlineplus	https://medlineplus.gov/genetics/condition/hartsfield-syndrome/	2021-01-27T08:25:25	{"gard": ["2725"], "mesh": ["C564484"], "omim": ["615465"], "synonyms": []}
A rare congenital aortic malformation characterized by an aortic valve with four cusps instead of the usual three. The cusps can be equal-sized or vary in size. The malformation is an isolated finding in the majority of cases but may also be associated with other cardiac anomalies. The most common complication is aortic regurgitation. Aortic stenosis is infrequently observed. Patients usually become symptomatic in the fifth to sixth decade of life and may present with palpitations, chest pain, dyspnea, fatigue, pedal edema, and syncope. In severe cases, congestive heart failure can be the presenting symptom. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Quadricuspid aortic valve	c0345002	28,529	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=542568	2021-01-23T18:16:19	{}
Weill-Marchesani syndrome is a disorder of connective tissue. Connective tissue forms the body's supportive framework, providing structure and strength to the muscles, joints, organs, and skin. The major signs and symptoms of Weill-Marchesani syndrome include short stature, eye abnormalities, unusually short fingers and toes (brachydactyly), and joint stiffness. Adult height for men with Weill-Marchesani syndrome ranges from 4 feet, 8 inches to 5 feet, 6 inches. Adult height for women with this condition ranges from 4 feet, 3 inches to 5 feet, 2 inches. An eye abnormality called microspherophakia is characteristic of Weill-Marchesani syndrome. This term refers to a small, sphere-shaped lens, which is associated with nearsightedness (myopia) that worsens over time. The lens also may be positioned abnormally within the eye (ectopia lentis). Many people with Weill-Marchesani syndrome develop glaucoma, an eye disease that increases the pressure in the eye and can lead to blindness. Occasionally, heart defects or an abnormal heart rhythm can occur in people with Weill-Marchesani syndrome. ## Frequency Weill-Marchesani syndrome appears to be rare; it has an estimated prevalence of 1 in 100,000 people. ## Causes Mutations in the ADAMTS10 and FBN1 genes can cause Weill-Marchesani syndrome. The ADAMTS10 gene provides instructions for making a protein whose function is unknown. This protein is important for normal growth before and after birth, and it appears to be involved in the development of the eyes, heart, and skeleton. Mutations in this gene disrupt the normal development of these structures, which leads to the specific features of Weill-Marchesani syndrome. A mutation in the FBN1 gene has also been found to cause Weill-Marchesani syndrome. The FBN1 gene provides instructions for making a protein called fibrillin-1. This protein is needed to form threadlike filaments, called microfibrils, that help provide strength and flexibility to connective tissue. The FBN1 mutation responsible for Weill-Marchesani syndrome leads to an unstable version of fibrillin-1. Researchers believe that the unstable protein interferes with the normal assembly of microfibrils, which weakens connective tissue and causes the abnormalities associated with Weill-Marchesani syndrome. In some people with Weill-Marchesani syndrome, no mutations in ADAMTS10 or FBN1 have been found. Researchers are looking for other genetic changes that may be responsible for the disorder in these people. ### Learn more about the genes associated with Weill-Marchesani syndrome * ADAMTS10 * FBN1 ## Inheritance Pattern Weill-Marchesani syndrome can be inherited in either an autosomal recessive or an autosomal dominant pattern. When Weill-Marchesani syndrome is caused by mutations in the ADAMTS10 gene, it has an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Other cases of Weill-Marchesani syndrome, including those caused by mutations in the FBN1 gene, have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the genetic change from one parent with the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Weill-Marchesani syndrome	c4552002	28,530	medlineplus	https://medlineplus.gov/genetics/condition/weill-marchesani-syndrome/	2021-01-27T08:25:05	{"gard": ["4936"], "omim": ["277600", "608328"], "synonyms": []}
A number sign (#) is used with this entry because Schimmelpenning-Feuerstein-Mims (SFM) syndrome can be caused by postzygotic somatic mutation in the HRAS (190020) gene on chromosome 11p15, the KRAS (190070) gene on chromosome 12p12, or the NRAS gene (164790) on chromosome 1p13. Isolated nevus sebaceous (see 162900) can be caused by somatic mutation in several genes, including HRAS and KRAS. Description Schimmelpenning-Feuerstein-Mims syndrome, also known as linear sebaceous nevus syndrome, is characterized by sebaceous nevi, often on the face, associated with variable ipsilateral abnormalities of the central nervous system, ocular anomalies, and skeletal defects (summary by Happle, 1991 and Ernst et al., 2007). The linear sebaceous nevi follow the lines of Blaschko (Hornstein and Knickenberg, 1974; Bouwes Bavinck and van de Kamp, 1985). All cases are sporadic. The syndrome is believed to be caused by an autosomal dominant lethal mutation that survives by somatic mosaicism (Gorlin et al., 2001). Clinical Features Feuerstein and Mims (1962) described 2 unrelated patients with linear nevus sebaceous of the midline of the face associated with epilepsy, focal EEG abnormalities, and mental retardation. Mehregan and Pinkus (1965) outlined the natural history of organoid nevi. The first stage is characterized by alopecia with absent or primitive hair follicles and numerous small hypoplastic sebaceous glands. At puberty, the lesions become verrucous with hyperplastic sebaceous glands. Benign or malignant tumors develop in later stages. Zaremba (1978) reviewed 37 reported cases of this disorder, described under different terms and eponyms. He also reviewed an original 19th century publication of Jadassohn and concluded that it was so good and extensive that his name deserved being attached to the disorder. He proposed that the condition be termed 'Jadassohn naevus phakomatosis' (JNP). Zaremba et al. (1978) reported 2 cases from their own experience. One of the patients required neurosurgical intervention, and histologic changes in the brain were reported. Baker et al. (1987) reported 4 patients with epidermal nevus syndrome and neurologic manifestations, including mental retardation, seizures, ophthalmologic anomalies, intracranial aneurysm, and porencephalic cyst. A review of 60 reported cases suggested that central nervous system complications were more likely associated with epidermal nevi on the head and that the anomalies were most often ipsilateral to the skin lesion. Monk and Vollum (1982) reported mother and daughter with nevus sebaceous of Jadassohn of the scalp. They suggested that this was the first familial occurrence reported. A similar condition, inflammatory linear verrucous epidermal nevus, was described by Hamm and Happle (1986) in mother and daughter. In a black man, his daughter and a granddaughter, Sahl (1990) described nevus sebaceus of the scalp. A basal cell carcinoma had arisen in the nevus in the grandfather. Benedetto et al. (1990) described the disorder in a boy and his maternal half brother. Dodge and Dobyns (1995) described a girl, born of unrelated parents, with sebaceous nevus syndrome, hemihypertrophy, coloboma of the left iris, talipes equinovarus, genu recurvatum, syndactyly 3-4 on the left foot, left hemimegalencephaly, and pachygyria. In addition, Dandy-Walker malformation and agenesis of the corpus callosum were found on cranial MRI. Consistent with the proposal by Happle (1991), Dodge and Dobyns (1995) suggested that sebaceous nevus syndrome may be caused by mosaic mutation of a gene that would be lethal if expressed in all cells. Heike et al. (2005) described a 19-year-old man with epidermal nevus syndrome who had right-sided linear skin lesions, generalized weakness, diffuse osteopenia associated with hypophosphatemic rickets, and distinctive focal bone lesions ipsilateral to the skin findings. The patient did not have the typical radiographic or histopathologic findings of fibrous dysplasia, although his circulating FGF23 (605380) level was elevated; screening of the GNAS gene (139320) revealed no mutation. Heike et al. (2005) reviewed 33 reported cases of ENS and systemic skeletal disease and found 8 (24%) involving distinctly asymmetric bone disease with more severe changes ipsilateral to the skin lesions. Heike et al. (2005) suggested that the focal skeletal disease, although different from fibrous dysplasia, may be a source of FGF23 in ENS. Hoffman et al. (2005) reported a 17.5-year-old man of Korean ancestry who had onset of linear nevus sebaceous syndrome before age 1 year. At 7 years of age, he developed hypophosphatemic rickets and exhibited a learning disability and an attention deficit disorder. Laboratory studies showed elevated plasma FGF23, a phosphaturic peptide. Treatment with the somatostatin (SST; 182450) agonist octreotide and excision of the nevus resulted in normalization of plasma FGF23 and clinical improvement. In addition, the patient had increased serum IgE levels, which decreased somewhat after octreotide and surgery. Hoffman et al. (2005) suggested that the hypophosphatemic rickets observed in linear nevus sebaceous syndrome is a type of tumor-induced osteomalacia resulting from a tumor-produced phosphaturic substance, and suggested that FGF23 and perhaps IgE are the mediators. Ernst et al. (2007) reported a 5-year-old girl with Schimmelpenning syndrome. She had an extensive, darkly pigmented, verrucous skin patch involving a large portion of the left side of her face and a smaller similar lesion on the right side. She also had a linear verrucoid lesion of the facial midline extending from the hairline to the chin. Neurologic involvement included blindness, seizures, and developmental delay. She presented with large mass in the left maxilla that was surgically removed and shown to be a central giant cell granuloma. About 1 year later, she developed a swelling on the right side of her face. Pathology showed foci of central giant cell granulomas and complex fibroosseous lesions in the maxilla, and an adenomatoid odontogenic tumor in the mandible. Hard tissue specimens from the mouth showed irregular accumulations of enamel, dentin, cementum, and pulp tissue, consistent with odontomas and foci of globular mineralized dentin. She also had multiple pigmented malformed teeth. Cytogenetic analysis of tissue from the second operation showed a complex karyotype with 62 to 68 chromosomes per cell; every chromosome pair had numerical or structural alterations. Eleven months later, another central giant cell granuloma was excised from the left maxilla. Zutt et al. (2003) reported a 52-year-old woman with Schimmelpenning-Feuerstein-Mims syndrome and hypophosphatemic rickets. At birth she was noted to have a large, right-sided nevus sebaceous following the lines of Blaschko and extending to her head, neck, arm, and trunk. The scalp was also involved, resulting in alopecia. The patient developed recurrent syringocystadenoma papilliferum and basal cell carcinoma within the nevus. Other features included generalized growth retardation, bone deformation due to rickets, exotropia and ophthalmoplegia of the left eye, corneal clouding, xanthelasmata on the eyelids, and precocious puberty. Intelligence was normal. She was treated with multiple dermabrasions over the years. Phosphaturia disappeared after a long period of time, and Zutt et al. (2003) postulated that a phosphaturic factor may have been produced by the nevus. There was no family history of a similar disorder. Inheritance Schimmelpenning-Feuerstein-Mims syndrome is believed to be caused by an autosomal dominant lethal mutation that survives by somatic mosaicism. All reported cases have occurred sporadically (Gorlin et al., 2001). Schworm et al. (1996) reported a pair of 5-year-old Turkish monozygotic twin girls discordant for SFM syndrome. The affected girl was noted at birth to have a right-sided skin nevus on the temple, and bilateral but asymmetric keratoconjunctival dermoids, more severe on the right. Skull radiographs were normal. At age 5 years, she had skin lesions limited to the scalp with associated frontoparietal alopecia. The right eye was more severely involved, with decreased visual acuity and esotropia. Mental development was age-appropriate. The other twin showed no signs of the disorder. The report supported the concept of a postzygotic somatic mutation in the etiology of the syndrome. Rijntjes-Jacobs et al. (2010) reported a second case of monozygotic twins discordant for SFM syndrome. The male monochorionic-diamniotic twins were born of a Dutch mother. The affected infant was noted to have several yellowish plaque skin lesions along the lines of Blaschko on the face, and severe eye abnormalities, including cryptophthalmus, coloboma, microcornea, and epibulbar lipodermoids. There was also a cleft palate and patent ductus arteriosus, and brain imaging suggested cerebral atrophy and calcifications. The child died on day 16 of life. The other twin was normal. The findings provided evidence for a postzygotic mutation as a pathogenetic mechanism. Pathogenesis Happle (1986) suggested that this condition may be explained by a dominant lethal gene arising as a somatic mutation in the early embryo or a gametic half-chromatid mutation and surviving by mosaicism. The experimental model in mice is the rescue of a lethal genotype by chimerism with a normal embryo (Bennett, 1978). Happle (1986) suggested a similar mechanism for the Proteus syndrome (176920) and the McCune-Albright syndrome (174800). Kousseff (1992) posited that JNP is, like other phakomatoses, a paracrine growth regulation disorder or paracrinopathy, i.e., dysregulation of paracrine growth and of transforming growth factors at cellular and extracellular matrix levels, leading to localized over- and undergrowth anomalies. For the deficiencies, he adopted the term used by Gomez (1988), i.e., hamartias, parallel to the term hamartomas. He reviewed 13 cases, including one of extraordinarily severe and widespread distribution. Molecular Genetics Groesser et al. (2012) analyzed tissue from 2 unrelated patients with Schimmelpenning-Feuerstein-Mims syndrome for RAS hotspot mutations. One patient (Zutt et al., 2003) carried a mutation in the HRAS gene (G13R; 190020.0017) and the other patient (Rijntjes-Jacobs et al., 2010) carried a mutation in the KRAS gene (G12D; 190070.0005). In both patients, the mutations were present in lesional tissue, including nevus sebaceous, but not in nonlesional skin or blood leukocytes, consistent with a somatic mosaic state. Functional analysis of mutant cells carrying the HRAS G13R mutation showed constitutive activation of the MAPK (see 176948) and PI3K (see 171834)/AKT (164730) signaling pathways. Somatic mutations in the HRAS and/or KRAS genes were also found in 97% of 65 isolated sebaceous nevi tissues. The authors postulated that the mosaic mutation likely extends to extracutaneous tissues in SFM compared to isolated sebaceous nevi, which could explain the phenotypic pleiotropy. Lim et al. (2014) identified a somatic NRAS mutation (Q61R; 164790.0002) in a 7-year-old Caucasian female who presented at birth with linear epidermal nevi on the left side of her body as well as dysplastic bone with a sclerotic appearance of the femur. INHERITANCE \- Somatic mosaicism GROWTH Height \- Short stature Other \- Growth retardation \- Asymmetric overgrowth HEAD & NECK Head \- Cranial asymmetry Eyes \- Lid lipodermoid \- Coloboma of eyelids, iris, and choroid \- Ophthalmoplegia (in some) \- Corneal clouding (in some) Teeth \- Pigmented, malformed teeth CARDIOVASCULAR Vascular \- Coarctation of aorta GENITOURINARY Kidneys \- Horseshoe kidney SKELETAL \- Osteopenia \- Recurrent fractures \- Bone deformities Spine \- Kyphoscoliosis Hands \- Finger abnormalities Feet \- Toe abnormalities SKIN, NAILS, & HAIR Skin \- Linear nevus sebaceous, often in midfacial area \- Lesions follow the lines of Blaschko \- Ichthyosis hystrix \- Nevus unius lateris \- Hemangioma \- Hypopigmentation Hair \- Alopecia within lesion NEUROLOGIC Central Nervous System \- Neurologic abnormalities in about 7% \- Mental retardation \- Seizures \- Hemimegalencephaly ENDOCRINE FEATURES \- Hypophosphatemic vitamin D-resistant rickets (in some) \- Precocious puberty (less common) NEOPLASIA \- Basal cell carcinoma \- Syringocystadenoma papilliferum \- Central giant cell granuloma \- Trichoblastoma LABORATORY ABNORMALITIES \- Phosphaturia (in some) \- Phosphaturia may disappear after a long period of time MISCELLANEOUS \- Onset of skin lesions at birth \- Extracutaneous manifestations are variable \- Secondary tumors develop within the skin lesions MOLECULAR BASIS \- Caused by mutation in the V-Ki-Ras2 kirsten rat sarcoma viral oncogene homolog gene (KRAS, 190070.0005 ) \- Caused by mutation in the V-Ha-Ras harvey rat sarcoma viral oncogene homolog gene (HRAS, 190020.0017 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	SCHIMMELPENNING-FEUERSTEIN-MIMS SYNDROME	c3854181	28,531	omim	https://www.omim.org/entry/163200	2019-09-22T16:37:23	{"omim": ["163200"], "orphanet": ["2612"], "synonyms": ["Alternative titles", "SFM SYNDROME", "LINEAR SEBACEOUS NEVUS SYNDROME", "SEBACEOUS NEVUS SYNDROME, LINEAR", "JADASSOHN NEVUS PHAKOMATOSIS", "NEVUS SEBACEUS OF JADASSOHN", "ORGANOID NEVUS PHAKOMATOSIS", "EPIDERMAL NEVUS SYNDROME, FORMERLY"]}
Tegumentary leishmaniasis due to the parasite Leishmania braziliensis occurs in 2 stages after the infected sandfly bite: (1) a primary cutaneous lesion followed by (2) a secondary mucosal involvement generally resulting in severe facial deformities. To assess genetic and environmental factors involved in the development of the cutaneous lesion, Alcais et al. (1997) performed a family study in a region of Bolivia where the disease is endemic. This study involved 118 nuclear families, each with at least 1 cutaneous affected subject; 41 families were of native origin, and 77 (designated 'migrant') had recently settled in the area. The investigators concluded that in the 77 migrant families a recessive major gene controlled the onset of the primary cutaneous lesion, with residual familial dependencies and age-genotype interaction. Penetrance estimation showed that young subjects were genetically more susceptible than older subjects, suggesting that this genetic component could concern mechanisms involved in the development of individual protection during childhood. There was a significant genetic heterogeneity according to the native or migrant origin of the families, and no major-gene effect was found in the native subsample. Leishmania parasites in Latin America cause cutaneous (CL) and mucocutaneous leishmaniasis (MCL). MCL is associated with persistent inflammatory immune responses. Parasites from MCL patients reproduce the metastatic phenotype in a hamster model. Using DNA microarray analysis and metastatic and nonmetastatic Leishmania guyanensis clones in infected and uninfected mouse bone marrow-derived macrophages, Ives et al. (2011) observed increased expression of Ccl5 (187011), Cxcl10 (147310), Ifnb (147640), Tnf (191160), and Il6 (147620) after infection with metastatic parasites compared with nonmetastatic parasites or parasites obtained from CL patients. Induction of these proinflammatory cytokines and chemokines occurred in a Tlr3 (603029)- and Trif (TICAM1; 607601)-dependent manner. Metastatic L. guyanensis expressed higher levels of a Leishmania double-stranded RNA virus, LRV1, and this virus alone induced high chemokine and cytokine expression. Mice lacking Tlr3 had decreased parasite burden and footpad swelling after infection compared with wildtype mice. Ives et al. (2011) concluded that recognition of LRV1 within metastatic Leishmania parasites promotes inflammation and subverts the immune response to Leishmania, leading to parasite persistence. Inheritance \- Autosomal recessive \- Heterogeneity \- Age dependent penetrance Skin \- Tegumentary leishmaniasis susceptibility ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	LEISHMANIASIS, TEGUMENTARY, SUSCEPTIBILITY TO	c2748501	28,532	omim	https://www.omim.org/entry/602068	2019-09-22T16:14:05	{"omim": ["602068"]}
EML4-ALK positive lung cancer Micrograph showing ALK positive lung adenocarcinoma. H&E stain. SpecialtyOncology EML4-ALK positive lung cancer is a primary malignant lung tumor whose cells contain a characteristic abnormal configuration of DNA wherein the echinoderm microtubule-associated protein-like 4 (EML4) gene is fused to the anaplastic lymphoma kinase (ALK) gene. This abnormal gene fusion leads to the production of a protein (EML4-ALK) that appears, in many cases, to promote and maintain the malignant behavior of the cancer cells.[1] The transforming EML4-ALK fusion gene was first reported in non-small cell lung carcinoma (NSCLC) in 2007.[2] ## Contents * 1 Signs and symptoms * 2 Diagnosis * 2.1 Classification * 3 Screening * 4 Treatment * 5 Prognosis * 6 Epidemiology * 7 References * 8 External links ## Signs and symptoms[edit] The signs and symptoms of this lung cancer variant seem to mimic those of the underlying major cell type.[citation needed] ## Diagnosis[edit] ### Classification[edit] Most lung carcinomas containing the EML4-ALK gene fusion are adenocarcinomas. Some studies suggest that the papillary adenocarcinoma and the signet ring cell adenocarcinoma[3] variants are more likely to carry this fused gene than other histological variants. ## Screening[edit] Micrograph showing an ALK positive adenocarcinoma of the lung. ALK immunostain. Screening for ALK positive lung cancer is now a standard of care in the United States and Canada. Screening can be done with immunostaining, FISH, or next-generation sequencing (NGS).[citation needed] ## Treatment[edit] Crizotinib is a targeted therapy (FDA approved in 2011), manufactured by Pfizer and marketed under the brand name Xalkori and Crizalk that targets the EML4/ALK fusion gene.[citation needed] Ceritinib is a second generation targeted therapy (FDA approved in 2014), manufactured by Novartis and sold under the brand name Zykadia that also targets the EML4 fusion gene, but as a second generation drug it has a smaller molecule that allows superior penetration of the Blood Brain Barrier (BBB) over Crizotinib and is more capable of protecting the Central Nervous System (CNS).[citation needed] Alectinib another second generation targeted therapy and was approved (for this) by Japan in 2014[4] and by US FDA in 2015.,[5] manufactured by Genentech and marketed under the brand name Alecensa. Brigatinib a second generation targeted therapy (FDA approved in 2017), manufactured by Takeda and is marketed under the brand name Alunbrig. Ensartinib is a second generation targeted therapy (trial drug X-396), manufactured by XCovery.[citation needed] Lorlatinib is a third generation targeted therapy (awaiting FDA approval under trial drug PF-6463922), manufactured by Pfizer.[citation needed] TPX-0005 is a new third generation targeted therapy drug trial.[citation needed] ## Prognosis[edit] Treatment with crizotinib achieves 60% response rate.[6] However, crizotinib showed no improvement on overall survival compared to chemotherapy.[7] This may be due to the fact that there was a 70% crossover rate to crizotinib in patients treated initially with chemotherapy.[8] Also, patients who tested negative for EML4/ALK fusion had a response rate to crizotinib of up to 35%.[9] ## Epidemiology[edit] EML4-ALK gene fusions occur almost exclusively in carcinomas arising in non-smokers.[10][11] About 4% of non-small-cell lung carcinomas involve an EML4-ALK tyrosine kinase fusion gene.[12] 4–6% of lung adenocarcinomas involve the fusion gene.[6] EML4-ALK mutation rarely occurs in combination with K-RAS or EGFR mutations. ## References[edit] 1. ^ Soda M, Choi YL, Enomoto M, et al. (August 2007). "Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer". Nature. 448 (7153): 561–6. Bibcode:2007Natur.448..561S. doi:10.1038/nature05945. PMID 17625570. S2CID 2172543. 2. ^ Sasaki T, Rodig SJ, Chirieac LR, Jänne PA (July 2010). "The biology and treatment of EML4-ALK non-small cell lung cancer". Eur. J. Cancer. 46 (10): 1773–80. doi:10.1016/j.ejca.2010.04.002. PMC 2888755. PMID 20418096. 3. ^ Koh Y, Kim DW, Kim TM, et al. (May 2011). "Clinicopathologic characteristics and outcomes of patients with anaplastic lymphoma kinase-positive advanced pulmonary adenocarcinoma: suggestion for an effective screening strategy for these tumors". J Thorac Oncol. 6 (5): 905–12. doi:10.1097/JTO.0b013e3182111461. PMID 21358343. S2CID 38377715. 4. ^ Japan becomes first country to approve Roche’s alectinib for people with a specific form of advanced lung cancer 5. ^ New Oral Therapy To Treat ALK-Positive Lung Cancer. Dec 2015 6. ^ a b Bayliss, R; Choi, J (March 2016). "Molecular mechanisms that underpin EML4-ALK driven cancers and their response to targeted drugs". Cellular and Molecular Life Sciences. 73 (6): 1209–1224. doi:10.1007/s00018-015-2117-6. PMC 4761370. PMID 26755435. 7. ^ https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/202570s019lbl.pdf 8. ^ Solomon, Benjamin J.; Mok, Tony; Kim, Dong-Wan; Wu, Yi-Long; Nakagawa, Kazuhiko; Mekhail, Tarek; Felip, Enriqueta; Cappuzzo, Federico; Paolini, Jolanda; Usari, Tiziana; Iyer, Shrividya; Reisman, Arlene; Wilner, Keith D.; Tursi, Jennifer; Blackhall, Fiona; PROFILE 1014 Investigators (2014). "First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer". New England Journal of Medicine. 371 (23): 2167–2177. doi:10.1056/NEJMoa1408440. hdl:2434/426878. PMID 25470694. 9. ^ https://www.accessdata.fda.gov/cdrh_docs/pdf11/P110012B.pdf 10. ^ Shaw AT, Yeap BY, Mino-Kenudson M, et al. (September 2009). "Clinical Features and Outcome of Patients With Non–Small-Cell Lung Cancer Who Harbor EML4-ALK". Journal of Clinical Oncology. 27 (26): 4247–4253. doi:10.1200/JCO.2009.22.6993. PMC 2744268. PMID 19667264. 11. ^ Martelli MP, Sozzi G, Hernandez L, et al. (February 2009). "EML4-ALK rearrangement in non-small cell lung cancer and non-tumor lung tissues". Am. J. Pathol. 174 (2): 661–70. doi:10.2353/ajpath.2009.080755. PMC 2630573. PMID 19147828. 12. ^ Kumar, V; Abbas AK; Aster JC (2013). "Chapter 5". Robbins Basic Pathology (9th ed.). Elsevier Saunders. p. 212. ISBN 978-1-4377-1781-5. ## External links[edit] * Entrez Gene EML4 echinoderm microtubule associated protein like 4 Homo sapiens [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	EML4-ALK positive lung cancer	None	28,533	wikipedia	https://en.wikipedia.org/wiki/EML4-ALK_positive_lung_cancer	2021-01-18T18:33:23	{"wikidata": ["Q5323525"]}
Phantom eye syndrome Anatomy of the eye. The external eye muscles are shown in red. SpecialtyPsychiatry, Neurology Duration11-15 days Frequency5% The phantom eye syndrome (PES) is a phantom pain in the eye and visual hallucinations after the removal of an eye (enucleation, evisceration). ## Contents * 1 Symptoms * 2 Pathogenesis * 2.1 Phantom pain and non-painful phantom sensations * 2.2 Visual hallucinations * 3 Treatment * 4 See also * 5 References * 6 External links ## Symptoms[edit] Many patients experience one or more phantom phenomena after the removal of the eye: * Phantom pain in the (removed) eye (prevalence: 26%)[1][2] * Non-painful phantom sensations[1][2] * Visual hallucinations. About 30% of patients report visual hallucinations of the removed eye.[1] Most of these hallucinations consist of basic perceptions (shapes, colors). In contrast, visual hallucinations caused by severe visual loss without removal of the eye itself (Charles Bonnet syndrome) are less frequent (prevalence 10%) and often consist of detailed images. ## Pathogenesis[edit] ### Phantom pain and non-painful phantom sensations[edit] Phantom pain and non-painful phantom sensations result from changes in the central nervous system due to denervation of a body part.[3][4] Phantom eye pain is considerably less common than phantom limb pain. The prevalence of phantom pain after limb amputation ranged from 50% to 78%. The prevalence of phantom eye pain, in contrast, is about 30%. Post-amputation changes in the cortical representation of body parts adjacent to the amputated limb are believed to contribute to the development of phantom pain and non-painful phantom sensations. One reason for the smaller number of patients with phantom eye pain compared with those with phantom limb pain may be the smaller cortical somatosensory representation of the eye compared with the limbs. In limb amputees, some,[5] but not all, studies have found a correlation between preoperative pain in the affected limb and postoperative phantom pain. There is a significant association between painful and non-painful phantom experiences, preoperative pain in the symptomatic eye and headache.[6] Based on the present data, it is difficult to determine if headaches or preoperative eye pain play a causal role in the development of phantom phenomena or if headache, preoperative eye pain, and postoperative phantom eye experiences are only epiphenomena of an underlying factor. However, a study in humans demonstrated that experimental pain leads to a rapid reorganization of the somatosensory cortex.[7] This study suggests that preoperative and postoperative pain may be an important co-factor for somatosensory reorganization and the development of phantom experiences. ### Visual hallucinations[edit] Enucleation of an eye and, similarly, retinal damage, lead to a cascade of events in the cortical areas receiving visual input. Cortical GABAergic (GABA: Gamma-aminobutyric acid) inhibition decreases, and cortical glutamatergic excitation increases, followed by increased visual excitability or even spontaneous activity in the visual cortex.[8] It is believed that spontaneous activity in the denervated visual cortex is the neural correlate of visual hallucinations. ## Treatment[edit] Treatment of painful phantom eye syndrome is provision of ocular prosthesis in the empty orbit.[2] ## See also[edit] * Visual system * Charles Bonnet syndrome * Phantom limb ## References[edit] 1. ^ a b c Sörös, P.; O. Vo; I.-W. Husstedt; S. Evers & H. Gerding (May 2003). "Phantom eye syndrome: Its prevalence, phenomenology, and putative mechanisms". Neurology. 60 (9): 1542–3. doi:10.1212/01.wnl.0000059547.68899.f5. PMID 12743251. S2CID 27474612. 2. ^ a b c Shah S.I.A (1994). "Painful Phantom Eye" (PDF). Pak J Ophthalmol. 10 (4 (Index Issue)): 77–78. 3. ^ Ramachandran, Vilayanur S.; W Hirstein (September 1998). "The perception of phantom limbs. The D. O. Hebb lecture". Brain. 121 (9): 1603–30. doi:10.1093/brain/121.9.1603. PMID 9762952. 4. ^ Nikolajsen, L.; T. S. Jensen (July 2001). "Phantom limb pain". British Journal of Anaesthesia. 87 (1): 107–16. doi:10.1093/bja/87.1.107. PMID 11460799. Retrieved 2008-09-23. 5. ^ Nikolajsen L, Ilkjaer S, Krøner K, Christensen JH, Jensen TS (September 1997). "The influence of preamputation pain on postamputation stump and phantom pain". Pain. 72 (3): 393–405. doi:10.1016/S0304-3959(97)00061-4. PMID 9313280. S2CID 24665497. 6. ^ Nicolodi, M.; R. Frezzotti; A. Diadori; A. Nuti; F. Sicuteri (June 1997). "Phantom eye: features and prevalence. The predisposing role of headache". Cephalalgia. 17 (4): 501–4. doi:10.1046/j.1468-2982.1997.1704501.x. PMID 9209770. S2CID 34799505. 7. ^ Sörös, Peter; Stefan Knecht; Carsten Bantel; Tanya Imai; Rainer Wüsten; Christo Pantev; Bernd Lütkenhöner; Hartmut Bürkle; Henning Henningsen (February 2001). "Functional reorganization of the human primary somatosensory cortex after acute pain demonstrated by magnetoencephalography". Neuroscience Letters. 298 (3): 195–8. doi:10.1016/S0304-3940(00)01752-3. PMID 11165440. S2CID 30936812. 8. ^ Eysel, Ulf T.; Georg Schweigart; Thomas Mittmann; Dirk Eyding; Ying Qu; Frans Vandesande; Guy Orban; Lutgarde Arckens (1999). "Reorganization in the visual cortex after retinal and cortical damage". Restorative Neurology and Neuroscience. 15 (2–3): 153–64. PMID 12671230. Archived from the original on 2013-01-29. Retrieved 2008-09-23. ## External links[edit] Classification D * ICD-10: G54.6, G54.7 * ICD-9-CM: 353.6 * Cole, Jonathan. "Phantom limb pain". Wellcome Trust. Archived from the original on 2008-09-12. Retrieved 2008-09-23. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Phantom eye syndrome	c4038876	28,534	wikipedia	https://en.wikipedia.org/wiki/Phantom_eye_syndrome	2021-01-18T19:09:13	{"umls": ["C4038876"], "icd-9": ["353.6"], "icd-10": ["G54.7", "G54.6"], "wikidata": ["Q3508908"]}
Gastric antral vascular ectasia Other namesWatermelon stomach, watermelon disease Endoscopic image of gastric antral vascular ectasia seen as a radial pattern around the pylorus before (top) and after (bottom) treatment with argon plasma coagulation SpecialtyGastroenterology SymptomsBleeding in the stomach and intestines, edema, dilated blood vessels Gastric antral vascular ectasia (GAVE) is an uncommon cause of chronic gastrointestinal bleeding or iron deficiency anemia.[1][2] The condition is associated with dilated small blood vessels in the pyloric antrum, which is a distal part of the stomach.[1] The dilated vessels result in intestinal bleeding.[3] It is also called watermelon stomach because streaky long red areas that are present in the stomach may resemble the markings on watermelon.[1][2][3][4] The condition was first discovered in 1952,[2] and reported in the literature in 1953.[5] Watermelon disease was first diagnosed by Wheeler et al. in 1979, and definitively described in four living patients by Jabbari et al. only in 1984.[4] As of 2011, the cause and pathogenesis are still not known.[4][6] However, there are several competing hypotheses as to various causes.[4] ## Contents * 1 Signs and symptoms * 2 Cause * 2.1 Associated conditions * 3 Pathogenesis * 4 Diagnosis * 4.1 Differential diagnosis * 5 Treatment * 5.1 Traditional treatments * 5.2 Medications * 5.3 Treatment of co-morbid conditions * 5.4 Surgery * 6 Epidemiology * 7 References * 8 Further reading * 9 External links ## Signs and symptoms[edit] Most patients who are eventually diagnosed with watermelon stomach come to a physician complaining of anemia and blood loss.[7] Sometimes, a patient may come to the physician because he or she notices blood in the stools—either melena (black and tarry stools) and/or hematochezia (red bloody stools).[7] ## Cause[edit] The literature, from 1953 through 2010, often cited that the cause of gastric antral vascular ectasia is unknown.[4][6][7] The causal connection between cirrhosis and GAVE has not been proven.[6] A connective tissue disease has been suspected in some cases.[7] Autoimmunity may have something to do with it,[8] as 25% of all sclerosis patients who had a certain anti-RNA marker have GAVE.[9] RNA autoimmunity has been suspected as a cause or marker since at least 1996.[8] Gastrin levels may indicate a hormonal connection.[6] ### Associated conditions[edit] Micrograph showing liver cirrhosis, a condition that often precedes hepatic encephalopathy. Trichrome stain. GAVE is associated with a number of conditions, including portal hypertension, chronic kidney failure, and collagen vascular diseases.[2][10][11] Watermelon stomach also occurs particularly with scleroderma,[2][12][13][14] and especially the subtype known as systemic sclerosis.[2][9] A full 5.7% of persons with sclerosis have GAVE, and 25% of all sclerosis patients who had a certain anti-RNA polymerase marker have GAVE.[9] In fact: > Most patients with GAVE suffer from liver cirrhosis, autoimmune disease, chronic kidney failure and bone marrow transplantation. The typical initial presentations range from occult bleeding causing transfusion-dependent chronic iron-deficiency anemia to severe acute gastrointestinal bleeding. > > — Masae Komiyama, et al., 2010.[10] The endoscopic appearance of GAVE is similar to portal hypertensive gastropathy, but is not the same condition, and may be concurrent with cirrhosis of the liver.[2][6][15][16] 30% of all patients have cirrhosis associated with GAVE.[6] Sjögren's syndrome has been associated with at least one patient.[17] The first case of ectopic pancreas associated with watermelon stomach was reported in 2010.[4] Patients with GAVE may have elevated gastrin levels.[6] The Genetic and Rare Diseases Information Center (GARD) states that pernicious anemia is one of the conditions associated with GAVE's,[18] and one separate study showed that over three-fourths of the patients in the study with GAVE's had some kind of Vitamin B12 deficiency including the associated condition pernicious anemia.[19] Intestinal permeability and diverticulitis may occur in some patients with GAVE. ## Pathogenesis[edit] GAVE is characterized by dilated capillaries in the lamina propria with fibrin thrombi. The main histomorphologic differential diagnosis is portal hypertension, which is often apparent from clinical findings. Research in 2010 has shown that anti-RNA polymerase III antibodies may be used as a risk marker for GAVE in systemic sclerosis patients.[9] ## Diagnosis[edit] Micrograph showing gastric antral vascular ectasia. A large spherical, eosinophilic (i.e. pink) fibrin thrombus is seen off-center right. Stomach biopsy. H&E stain. GAVE is usually diagnosed definitively by means of an endoscopic biopsy.[6][7][10][20] The tell-tale watermelon stripes show up during the endoscopy.[7] Surgical exploration of the abdomen may be needed to diagnose some cases, especially if the liver or other organs are involved.[4] ### Differential diagnosis[edit] GAVE results in intestinal bleeding similar to duodenal ulcers and portal hypertension.[3][6] The GI bleeding can result in anemia.[6][7] It is often overlooked, but can be more common in elderly patients.[3][7] It has been seen in a female patient of 26 years of age.[6] Watermelon stomach has a different etiology and has a differential diagnosis from portal hypertension.[6][15] In fact, cirrhosis and portal hypertension may be missing in a patient with GAVE.[6] The differential diagnosis is important because treatments are different.[3][6][7][10] ## Treatment[edit] ### Traditional treatments[edit] GAVE is treated commonly by means of an endoscope, including argon plasma coagulation and electrocautery.[6][7][21] Since endoscopy with argon photocoagulation is "usually effective", surgery is "usually not required".[7] Coagulation therapy is well tolerated but "tends to induce oozing and bleeding."[7] "Endoscopy with thermal ablation" is favored medical treatment because of its low side effects and low mortality, but is "rarely curative."[6] Treatment of GAVE can be categorized into endoscopic, surgical and pharmacologic. Surgical treatment is definitive but it is rarely done nowadays with the variety of treatment options available. Some of the discussed modalities have been used in GAVE patients with another underlying disease rather than SSc; they are included as they may be tried in resistant SSc-GAVE patients. Symptomatic treatment includes iron supplementation and blood transfusion for cases with severe anemia, proton pump inhibitors may ameliorate the background chronic gastritis and minute erosions that commonly co-existed in biopsy reports.[11] ### Medications[edit] Other medical treatments have been tried and include estrogen and progesterone therapy,[21] Corticostreoids are effective, but are "limited by their side effects."[7] ### Treatment of co-morbid conditions[edit] A transjugular intrahepatic portosystemic shunt (TIPS or TIPSS) procedure is used to treat portal hypertension when that is present as an associated condition. Unfortunately, the TIPSS, which has been used for similar conditions, may cause or exacerbate hepatic encephalopathy.[22][23] TIPSS-related encephalopathy occurs in about 30% of cases, with the risk being higher in those with previous episodes of encephalopathy, higher age, female sex, and liver disease due to causes other than alcohol.[24] The patient, with his or her physician and family, must balance out a reduction in bleeding caused by TIPS with the significant risk of encephalopathy.[22][23][24] Various shunts have been shown in a meta-study of 22 studies to be effective treatment to reduce bleeding, yet none have any demonstrated survival advantage.[22] If there is cirrhosis of the liver that has progressed to liver failure, then lactulose may be prescribed for hepatic encephalopathy, especially for Type C encephalopathy with diabetes.[24] Also, "antibiotics such as neomycin, metronidazole, and rifaximin" may be used effectively to treat the encephalopathy by removing nitrogen-producing bacteria from the gut.[24] Paracentesis, a medical procedure involving needle drainage of fluid from a body cavity,[25] may be used to remove fluid from the peritoneal cavity in the abdomen for such cases.[23] This procedure uses a large needle, similar to the better-known amniocentesis. ### Surgery[edit] Surgery, consisting of excision of part of the lower stomach, also called antrectomy, is another option.[6][16] Antrectomy is "the resection, or surgical removal, of a part of the stomach known as the antrum".[2] Laparoscopic surgery is possible in some cases, and as of 2003, was a "novel approach to treating watermelon stomach".[26] A treatment used sometimes is endoscopic band ligation.[27] In 2010, a team of Japanese surgeons performed a "novel endoscopic ablation of gastric antral vascular ectasia".[10] The experimental procedure resulted in "no complications".[10] Relapse is possible, even after treatment by argon plasma coagulation and progesterone.[21] Antrectomy or other surgery is used as a last resort for GAVE.[2][6][7][10][15][16] ## Epidemiology[edit] The average age of diagnosis for GAVE is 73 years of age for females,[3][7] and 68 for males.[2] Women are about twice as often diagnosed with gastric antral vascular ectasia than men.[2][7] 71% of all cases of GAVE are diagnosed in females.[3][7] Patients in their thirties have been found to have GAVE.[6] It becomes more common in women in their eighties, rising to 4% of all such gastrointestinal conditions.[10] 5.7% of all sclerosis patients (and 25% of those who had a certain anti-RNA marker) have GAVE.[9] ## References[edit] 1. ^ a b c Suit, PF; Petras, RE; Bauer, TW; Petrini Jr, JL (1987). "Gastric antral vascular ectasia. A histologic and morphometric study of "the watermelon stomach"". The American Journal of Surgical Pathology. 11 (10): 750–7. doi:10.1097/00000478-198710000-00002. PMID 3499091. 2. ^ a b c d e f g h i j k Surgery Encyclopedia website page on Antrectomy. Accessed September 29, 2010. 3. ^ a b c d e f g Nguyen, Hien; Le, Connie; Nguyen, Hanh (2009). "Gastric antral vascular ectasia (watermelon stomach)-an enigmatic and often-overlooked cause of gastrointestinal bleeding in the elderly". The Permanente Journal. 13 (4): 46–9. doi:10.7812/TPP/09-055. PMC 2911825. PMID 20740102. 4. ^ a b c d e f g Yildiz, Baris; Sokmensuer, Cenk; Kaynaroglu, Volkan (2010). "Chronic anemia due to watermelon stomach". Annals of Saudi Medicine. 30 (2): 156–8. doi:10.4103/0256-4947.60524. PMC 2855069. PMID 20220268. 5. ^ Rider, JA; Klotz, AP; Kirsner, JB (1953). "Gastritis with veno-capillary ectasia as a source of massive gastric hemorrhage". Gastroenterology. 24 (1): 118–23. doi:10.1016/S0016-5085(53)80070-3. PMID 13052170. 6. ^ a b c d e f g h i j k l m n o p q r s Tuveri, Massimiliano; Borsezio, Valentina; Gabbas, Antonio; Mura, Guendalina (2007). "Gastric antral vascular ectasia—an unusual cause of gastric outlet obstruction: report of a case". Surgery Today. 37 (6): 503–5. doi:10.1007/s00595-006-3430-3. PMID 17522771. 7. ^ a b c d e f g h i j k l m n o p q Rosenfeld, G; Enns, R (2009). "Argon photocoagulation in the treatment of gastric antral vascular ectasia and radiation proctitis". Canadian Journal of Gastroenterology. 23 (12): 801–4. doi:10.1155/2009/374138. PMC 2805515. PMID 20011731. 8. ^ a b Valdez, BC; Henning, D; Busch, RK; Woods, K; Flores-Rozas, H; Hurwitz, J; Perlaky, L; Busch, H (1996). "A nucleolar RNA helicase recognized by autoimmune antibodies from a patient with watermelon stomach disease". Nucleic Acids Research. 24 (7): 1220–4. doi:10.1093/nar/24.7.1220. PMC 145780. PMID 8614622. 9. ^ a b c d e Ceribelli, A; Cavazzana, I; Airò, P; Franceschini, F (2010). "Anti-RNA polymerase III antibodies as a risk marker for early gastric antral vascular ectasia (GAVE) in systemic sclerosis" (PDF). The Journal of Rheumatology. 37 (7): 1544. doi:10.3899/jrheum.100124. PMID 20595295. 10. ^ a b c d e f g h Komiyama, Masae; Fu, K; Morimoto, T; Konuma, H; Yamagata, T; Izumi, Y; Miyazaki, A; Watanabe, S (2010). "A novel endoscopic ablation of gastric antral vascular ectasia". World Journal of Gastrointestinal Endoscopy. 2 (8): 298–300. doi:10.4253/wjge.v2.i8.298. PMC 2999147. PMID 21160630. 11. ^ a b El-Gendy, Hala; Shohdy, Kyrillus S.; Maghraby, Gehad G.; Abadeer, Kerolos; Mahmoud, Moustafa (2017-02-01). "Gastric antral vascular ectasia in systemic sclerosis: Where do we stand?". International Journal of Rheumatic Diseases. 20 (12): 2133–2139. doi:10.1111/1756-185X.13047. ISSN 1756-185X. PMID 28217887. 12. ^ Scleroderma Association website Archived 2015-05-07 at the Wayback Machine. Accessed September 29, 2010. 13. ^ Marie, I.; Ducrotte, P.; Antonietti, M.; Herve, S.; Levesque, H. (2008). "Watermelon stomach in systemic sclerosis: its incidence and management". Alimentary Pharmacology & Therapeutics. 28 (4): 412–421. doi:10.1111/j.1365-2036.2008.03739.x. PMID 18498445. 14. ^ Ingraham, KM; O'Brien, MS; Shenin, M; Derk, CT; Steen, VD (2010). "Gastric antral vascular ectasia in systemic sclerosis: demographics and disease predictors". The Journal of Rheumatology. 37 (3): 603–7. doi:10.3899/jrheum.090600. PMID 20080908. 15. ^ a b c Spahr, L; Villeneuve, J-P; Dufresne, M-P; Tasse, D; Bui, B; Willems, B; Fenyves, D; Pomier-Layrargues, G (1999). "Gastric antral vascular ectasia in cirrhotic patients: absence of relation with portal hypertension". Gut. 44 (5): 739–42. doi:10.1136/gut.44.5.739. PMC 1727493. PMID 10205216. 16. ^ a b c Spahr, L; Villeneuve, JP; Dufresne, MP; Tassé, D; Bui, B; Willems, B; Fenyves, D; Pomier-Layrargues, G (1999). "Gastric antral vascular ectasia in cirrhotic patients: absence of relation with portal hypertension". Gut. 44 (5): 739–42. doi:10.1136/gut.44.5.739. PMC 1727493. PMID 10205216. 17. ^ Krstić, M; Alempijević, T; Andrejević, S; Zlatanović, M; Damjanov, N; Ivanović, B; Jovanović, I; Tarabar, D; Milosavljević, T (2010). "Watermelon stomach in a patient with primary Sjögren's syndrome". Vojnosanitetski Pregled. Military-medical and Pharmaceutical Review. 67 (3): 256–8. doi:10.2298/VSP1003256K. PMID 20361704. 18. ^ "Watermelon Stomach"Genetic and Rare Diseases Information Center (GARD), National Institution of Health. 19. ^ "Watermelon Stomach and Radiiation Proctopathy CCS Publishing, August 1, 2011 20. ^ Gilliam, John H.; Geisinger, Kim R.; Wu, Wallace C.; Weidner, Noel; Richter, Joel E. (1989). "Endoscopic biopsy is diagnostic in gastric antral vascular ectasia". Digestive Diseases and Sciences. 34 (6): 885–8. doi:10.1007/BF01540274. PMID 2721320. 21. ^ a b c Shibukawa, G; Irisawa, A; Sakamoto, N; Takagi, T; Wakatsuki, T; Imamura, H; Takahashi, Y; Sato, A; et al. (2007). "Gastric antral vascular ectasia (GAVE) associated with systemic sclerosis: relapse after endoscopic treatment by argon plasma coagulation". Internal Medicine (Tokyo, Japan). 46 (6): 279–83. doi:10.2169/internalmedicine.46.6203. PMID 17379994. 22. ^ a b c Khan S, Tudur Smith C, Williamson P, Sutton R (2006). "Portosystemic shunts versus endoscopic therapy for variceal rebleeding in patients with cirrhosis". The Cochrane Database of Systematic Reviews (4): CD000553. doi:10.1002/14651858.CD000553.pub2. PMC 7045742. PMID 17054131. 23. ^ a b c Saab S, Nieto JM, Lewis SK, Runyon BA (2006). "TIPS versus paracentesis for cirrhotic patients with refractory ascites". The Cochrane Database of Systematic Reviews (4): CD004889. doi:10.1002/14651858.CD004889.pub2. PMID 17054221. 24. ^ a b c d Sundaram V, Shaikh OS (July 2009). "Hepatic encephalopathy: pathophysiology and emerging therapies". Med. Clin. North Am. 93 (4): 819–36, vii. doi:10.1016/j.mcna.2009.03.009. PMID 19577116. 25. ^ "paracentesis" at Dorland's Medical Dictionary 26. ^ Sherman, V; Klassen, DR; Feldman, LS; Jabbari, M; Marcus, V; Fried, GM (2003). "Laparoscopic antrectomy: a novel approach to treating watermelon stomach". Journal of the American College of Surgeons. 197 (5): 864–7. doi:10.1016/S1072-7515(03)00600-8. PMID 14585429. 27. ^ Wells, C; Harrison, M; Gurudu, S; Crowell, M; Byrne, T; Depetris, G; Sharma, V (2008). "Treatment of gastric antral vascular ectasia (watermelon stomach) with endoscopic band ligation". Gastrointestinal Endoscopy. 68 (2): 231–6. doi:10.1016/j.gie.2008.02.021. PMID 18533150. ## Further reading[edit] * Thonhofer, R; Siegel, C; Trummer, M; Gugl, A (2010). "Clinical images: Gastric antral vascular ectasia in systemic sclerosis". Arthritis and Rheumatism. 62 (1): 290. doi:10.1002/art.27185. PMID 20039398. ## External links[edit] Classification D * ICD-10: K31.8 * ICD-9-CM: 537.82 * MeSH: D020252 * DiseasesDB: 29505 * v * t * e Diseases of the digestive system Upper GI tract Esophagus * Esophagitis * Candidal * Eosinophilic * Herpetiform * Rupture * Boerhaave syndrome * Mallory–Weiss syndrome * UES * Zenker's diverticulum * LES * Barrett's esophagus * Esophageal motility disorder * Nutcracker esophagus * Achalasia * Diffuse esophageal spasm * Gastroesophageal reflux disease (GERD) * Laryngopharyngeal reflux (LPR) * Esophageal stricture * Megaesophagus * Esophageal intramural pseudodiverticulosis Stomach * Gastritis * Atrophic * Ménétrier's disease * Gastroenteritis * Peptic (gastric) ulcer * Cushing ulcer * Dieulafoy's lesion * Dyspepsia * Pyloric stenosis * Achlorhydria * Gastroparesis * Gastroptosis * Portal hypertensive gastropathy * Gastric antral vascular ectasia * Gastric dumping syndrome * Gastric volvulus * Buried bumper syndrome * Gastrinoma * Zollinger–Ellison syndrome Lower GI tract Enteropathy Small intestine (Duodenum/Jejunum/Ileum) * Enteritis * Duodenitis * Jejunitis * Ileitis * Peptic (duodenal) ulcer * Curling's ulcer * Malabsorption: Coeliac * Tropical sprue * Blind loop syndrome * Small bowel bacterial overgrowth syndrome * Whipple's * Short bowel syndrome * Steatorrhea * Milroy disease * Bile acid malabsorption Large intestine (Appendix/Colon) * Appendicitis * Colitis * Pseudomembranous * Ulcerative * Ischemic * Microscopic * Collagenous * Lymphocytic * Functional colonic disease * IBS * Intestinal pseudoobstruction / Ogilvie syndrome * Megacolon / Toxic megacolon * Diverticulitis/Diverticulosis/SCAD Large and/or small * Enterocolitis * Necrotizing * Gastroenterocolitis * IBD * Crohn's disease * Vascular: Abdominal angina * Mesenteric ischemia * Angiodysplasia * Bowel obstruction: Ileus * Intussusception * Volvulus * Fecal impaction * Constipation * Diarrhea * Infectious * Intestinal adhesions Rectum * Proctitis * Radiation proctitis * Proctalgia fugax * Rectal prolapse * Anismus Anal canal * Anal fissure/Anal fistula * Anal abscess * Hemorrhoid * Anal dysplasia * Pruritus ani GI bleeding * Blood in stool * Upper * Hematemesis * Melena * Lower * Hematochezia Accessory Liver * Hepatitis * Viral hepatitis * Autoimmune hepatitis * Alcoholic hepatitis * Cirrhosis * PBC * Fatty liver * NASH * Vascular * Budd–Chiari syndrome * Hepatic veno-occlusive disease * Portal hypertension * Nutmeg liver * Alcoholic liver disease * Liver failure * Hepatic encephalopathy * Acute liver failure * Liver abscess * Pyogenic * Amoebic * Hepatorenal syndrome * Peliosis hepatis * Metabolic disorders * Wilson's disease * Hemochromatosis Gallbladder * Cholecystitis * Gallstone / Cholelithiasis * Cholesterolosis * Adenomyomatosis * Postcholecystectomy syndrome * Porcelain gallbladder Bile duct/ Other biliary tree * Cholangitis * Primary sclerosing cholangitis * Secondary sclerosing cholangitis * Ascending * Cholestasis/Mirizzi's syndrome * Biliary fistula * Haemobilia * Common bile duct * Choledocholithiasis * Biliary dyskinesia * Sphincter of Oddi dysfunction Pancreatic * Pancreatitis * Acute * Chronic * Hereditary * Pancreatic abscess * Pancreatic pseudocyst * Exocrine pancreatic insufficiency * Pancreatic fistula Other Hernia * Diaphragmatic * Congenital * Hiatus * Inguinal * Indirect * Direct * Umbilical * Femoral * Obturator * Spigelian * Lumbar * Petit's * Grynfeltt-Lesshaft * Undefined location * Incisional * Internal hernia * Richter's Peritoneal * Peritonitis * Spontaneous bacterial peritonitis * Hemoperitoneum * Pneumoperitoneum [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Gastric antral vascular ectasia	c0267211	28,535	wikipedia	https://en.wikipedia.org/wiki/Gastric_antral_vascular_ectasia	2021-01-18T18:31:20	{"gard": ["7877"], "mesh": ["D020252"], "umls": ["C0267211"], "icd-9": ["537.82"], "icd-10": ["K31.88"], "wikidata": ["Q1484679"]}
A number sign (#) is used with this entry because of evidence that congenital interstitial lung disease with nephrotic syndrome and epidermolysis bullosa (ILNEB) is caused by homozygous mutation in the ITGA3 gene (605025) on chromosome 17q21. Description Mutations in the integrin alpha-3 gene are associated with disrupted basement-membrane structures and compromised barrier functions in kidney, lung, and skin. Patients exhibit a multiorgan disorder that includes congenital interstitial lung disease, nephrotic syndrome, and epidermolysis bullosa. The respiratory and renal features predominate, and lung involvement accounts for the lethal course of the disease (summary by Has et al., 2012). Clinical Features Has et al. (2012) described 3 unrelated children, a boy and 2 girls, who had congenital interstitial lung disease, nephrotic syndrome, and mild epidermolysis bullosa. The index patient was a boy from southern Italy who had respiratory distress at birth requiring high-flow supplemental oxygen; chest x-ray showed severe reticulonodular changes. At 2 weeks of age, he developed renal failure and nephrotic syndrome, and peritoneal dialysis was initiated. From the age of 3 months, the infant had increasing skin fragility, with small blisters and erosions after mechanical manipulation. There was no mucosal involvement. Scalp hair, eyebrows, and eyelashes were fine and sparse. The big toenails became dystrophic, and distal onycholysis followed mild trauma to the fingernails. Renal biopsy at 1 month of age showed globally atrophic glomeruli, focal segmental glomerulosclerosis, diffuse interstitial fibrosis, tubular atrophy, and loss and immaturity of the tubules. At 5.5 months, lung biopsy showed hyperinflation and mild to moderate simplification of air spaces and mild reactive changes in the bronchioles. The infant died at 7.5 months during an episode of pulmonary infection. The second patient was a girl born to healthy consanguineous parents from Gaza, the only affected of 9 sibs, who developed respiratory distress at 2 days of life. At 6 weeks of age, chest x-ray showed bilateral infiltrates, and CT findings were consistent with diffuse interstitial lung disease. Laboratory tests showed proteinuria in the nephrotic range, and peritoneal dialysis was begun. The girl died of multiorgan failure at 2 months of age. The third patient was a Pakistani girl, born to healthy consanguineous parents, who developed fever and respiratory distress at 2 months of age; chest x-ray showed changes consistent with right upper and middle lobe pneumonia. Proteinuria in the nephrotic range was noted, and a renal biopsy at 5 months of age showed focal segmental glomerulosclerosis. Progressive renal function deterioration required peritoneal dialysis at 17 months of age. She had recurrent respiratory infections and required supplemental oxygen to maintain peripheral saturation above 90%. At 4 months of age, she developed annular erythematous skin lesions that coalesced into blisters that were consistent with epidermolysis bullosa. She died of multiorgan failure at 19 months of age. Yalcin et al. (2015) reported a male infant, born of consanguineous parents, who presented in the first week of life with respiratory distress and cyanosis in the absence of evidence of infection with microorganisms. Lung imaging was consistent with interstitial lung disease, and biopsy showed abnormal alveolarization and poorly septated alveolar spaces. Laboratory studies showed nephrotic-range proteinuria and hypoalbuminemia associated with crossed fused renal ectopia. The patient had fine sparse scalp hair and dystrophic nails, but no overt clinical skin disease. Skin biopsy showed a junctional split. He died at age 6.5 months of respiratory infection. Pathogenesis Has et al. (2012) analyzed skin samples from an Italian boy who had mild epidermolysis bullosa associated with congenital interstitial lung disease and nephrotic syndrome. Light microscopy showed a flat epidermis without rete ridges, and subepidermal blisters were present. Transmission electron microscopy showed a thin lamina densa that was discontinuous between the hemidesmosomes. Keratin filaments, desmosomes, hemidesmosomes, and anchoring fibrils appeared to be normal. Immunofluorescence mapping revealed focal disruption of the dermal-epidermal junction with cleavage within the basement membrane. Has et al. (2012) noted that these changes did not correspond to any known type of epidermolysis bullosa in humans, but bore a striking resemblance to the findings described in the integrin alpha-3 (ITGA3; 605025) knockout mouse. Molecular Genetics In an Italian boy with congenital interstitial lung disease, nephrotic syndrome, and mild epidermolysis bullosa, who died at 7.5 months of age of a lung infection, Has et al. (2012) excluded mutation in the NPHS2 (604766) and WT1 (607102) genes as a cause of the nephrotic syndrome and also ruled out mutation in the CFTR (602421) and ABCA3 (601615) genes as a cause of the interstitial lung disease. The authors observed that patient skin samples resembled those of the integrin alpha-3 knockout mouse, and a lack of ITGA3 immunoreactivity in patient tissue samples was confirmed. Direct sequencing of patient DNA revealed homozygosity for a 1-bp deletion in the ITGA3 gene (605025.0001) that was present in heterozygosity in the unaffected parents. Analysis of ITGA3 in 2 similarly affected unrelated girls revealed homozygosity for a splice site and a missense mutation (605025.0002 and 605025.0003). In a male infant with ILNEB, Yalcin et al. (2015) identified a homozygous missense mutation in the ITGA3 gene (R463W; 605025.0004). Studies of patient cells indicated that the mutant protein did not undergo proper processing of N-linked oligosaccharides. There was intracellular accumulation of ITGA3, lack of expression at the cell membrane, and no association with the ITGB1 (135630) subunit. The findings suggested that the mutation caused impaired posttranslational processing of ITGA3. INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Microcephaly Face \- Round face \- Prominent forehead \- Retrognathism Ears \- Large ears Eyes \- Fine eyebrows \- Sparse eyebrows \- Sparse eyelashes \- Hypertelorism \- Antimongoloid slant Nose \- Prominent nose with long saddle Mouth \- Small mouth RESPIRATORY Lung \- Interstitial lung disease (seen in all patients) \- Respiratory distress, neonatal (seen in all patients) \- Recurrent respiratory infections CHEST External Features \- Narrow chest Breasts \- Gynecomastia GENITOURINARY Kidneys \- Nephrotic syndrome, congenital (seen in all patients) \- Renal failure \- Focal segmental glomerulosclerosis \- Diffuse interstitial fibrosis \- Tubular atrophy \- Tubular immaturity SKELETAL Skull \- Microcephaly Hands \- Clinodactyly, discrete Feet \- Deep furrows of soles SKIN, NAILS, & HAIR Skin \- Fragile skin \- Blisters and erosions after mechanical manipulation \- Residual erythema after healing Skin Histology \- Flat epidermis without rete ridges \- Subepidermal blisters \- Focal disruption of dermal-epidermal junction, with cleavage within the basement membrane Electron Microscopy \- Basement membrane abnormalities \- Thin lamina densa \- Discontinuities between hemidesmosomes Nails \- Dystrophic nails \- Distal onycholysis following minor trauma Hair \- Fine hair \- Sparse scalp hair \- Sparse eyebrows \- Sparse eyelashes MUSCLE, SOFT TISSUES \- Mild muscular hypotonia NEUROLOGIC Central Nervous System \- Mild muscular hypotonia \- Delayed neurologic development \- Normal psychosocial and cognitive development VOICE \- Shrill cry LABORATORY ABNORMALITIES \- Proteinuria (seen in all patients) \- Hypoalbuminemia \- Decreased glomerular filtration rate (seen in all patients) \- Respiratory acidosis MISCELLANEOUS \- Four unrelated patients reported (last curated August 2015) \- Variable phenotype \- Patients die in infancy due to infectious complications MOLECULAR BASIS \- Caused by mutation in the alpha-3 integrin gene (ITGA3, 605025.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	INTERSTITIAL LUNG DISEASE, NEPHROTIC SYNDROME, AND EPIDERMOLYSIS BULLOSA, CONGENITAL	c3553636	28,536	omim	https://www.omim.org/entry/614748	2019-09-22T15:54:19	{"omim": ["614748"], "orphanet": ["306504"], "synonyms": ["Congenital ILNEB syndrome", "Congenital NEP syndrome", "Congenital interstitial lung disease-nephrotic syndrome-epidermolysis bullosa syndrome", "Congenital nephrotic syndrome-epidermolysis bullosa-pulmonary disease syndrome", "Congenital nephrotic syndrome-interstitial lung disease-epidermolysis bullosa syndrome", "JEB with respiratory and renal involvement", "JEB-RR"]}
Cataract-deafness-hypogonadism syndrome is an extremely rare multiple congenital abnormality syndrome, described in only three brothers to date, that is characterized by the association of congenital cataract, sensorineural deafness, hypogonadism, mild intellectual deficit, hypertrichosis, and short stature. There have been no further descriptions in the literature since 1995. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Cataract-deafness-hypogonadism syndrome	c2931269	28,537	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1383	2021-01-23T18:43:38	{"gard": ["248"], "mesh": ["C536626"], "umls": ["C2931269"], "icd-10": ["Q87.8"], "synonyms": ["Cataract-hearing loss-hypogonadism syndrome", "Schaap-Taylor-Baraitser syndrome"]}
This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Vitelliform macular dystrophy" – news · newspapers · books · scholar · JSTOR (July 2016) (Learn how and when to remove this template message) Vitelliform macular dystrophy Other namesVitelliform dystrophy Best disease, the early-onset form of vitelliform macular dystrophy, has an autosomal dominant pattern of inheritance. SpecialtyOphthalmology, medical genetics Vitelliform macular dystrophy, is an irregular autosomal dominant eye disorder which can cause progressive vision loss. This disorder affects the retina, specifically cells in a small area near the center of the retina called the macula. The macula is responsible for sharp central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. The condition is characterized by yellow (or orange), slightly elevated, round structures similar to the yolk (Latin vitellus) of an egg.[1] ## Contents * 1 Genetics * 2 Pathophysiology * 3 Diagnosis * 4 References * 5 Further reading * 6 External links ## Genetics[edit] Best disease is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition. The inheritance pattern of adult-onset vitelliform macular dystrophy is definitively autosomal dominant.[1] Many affected people, however, have no history of the disorder in their family and only a small number of affected families have been reported. This is because the penetrance of the condition is incomplete; therefore, it is possible for an individual to have a copy of the mutant allele and not display the VMD phenotype. The ratio of males to females is approximately 1:1.[1] ## Pathophysiology[edit] Mutations in the RDS and VMD2 genes cause vitelliform macular dystrophy. Mutations in the VMD2 gene are responsible for Best disease. Changes in either the VMD2 or RDS gene can cause the adult-onset form of vitelliform macular dystrophy; however, fewer than a quarter of cases result from mutations in these two genes. In most cases, the cause of the adult-onset form is unknown. The VMD2 gene provides instructions for making a protein called bestrophin. Although its exact function is uncertain, this protein likely acts as a channel that controls the movement of negatively charged chlorine atoms (chloride ions) into or out of cells in the retina. Mutations in the VMD2 gene probably lead to the production of an abnormally shaped channel that cannot regulate the flow of chloride. Researchers have not determined how these malfunctioning channels are related to the buildup of lipofuscin in the macula and progressive vision loss. The RDS gene provides instructions for making a protein called peripherin. This protein is essential for the normal function of light-sensing (photoreceptor) cells in the retina. Mutations in the RDS gene disrupt the structures in these cells that contain light-sensing pigments, leading to vision loss. It is unclear why RDS mutations affect only central vision in people with adult-onset vitelliform macular dystrophy. ## Diagnosis[edit] Vitelliform macular dystrophy causes a fatty yellow pigment (lipofuscin) to build up in cells underlying the macula. The retinal pigment epithelium also degenerates. Over time, the abnormal accumulation of this substance can damage the cells that are critical for clear central vision. As a result, people with this disorder often lose their central vision and may experience blurry or distorted vision, and loss is rarely symmetric. Scotomata appear, first with red light and then for green; finally, relative (or in more serious cases, absolute) scotomata occur with white light. Vitelliform macular dystrophy does not affect side (peripheral) vision or the ability to see at night. Researchers have described two forms of vitelliform macular dystrophy with similar features. The early-onset form (known as Best disease) usually appears in childhood; however, the onset of symptoms and the severity of vision loss vary widely. The adult-onset form begins later, usually in middle age, and tends to cause relatively mild vision loss. The two forms of vitelliform macular dystrophy each have characteristic changes in the macula that can be detected during an eye examination. ## References[edit] 1. ^ a b c Deutman A, Hoyng C, van Lith-Verhoeven J (2006). "Macular dystrophies". Retina (4 ed.). Elsevier Mosby. pp. 1177–81. ## Further reading[edit] * MacDonald IM, Lee T (December 2003). "Best Vitelliform Macular Dystrophy". In Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Stephens K, Amemiya A, MacDonald IM, Lee T (eds.). GeneReviews. Seattle (WA): University of Washington, Seattle. PMID 20301346. * George Priya Doss C, Chakraborty C, Monford Paul Abishek N, Thirumal Kumar D, Narayanan V (2014). "Application of evolutionary based in silico methods to predict the impact of single amino acid substitutions in vitelliform macular dystrophy". Advances in Protein Chemistry and Structural Biology. 94: 177–267. doi:10.1016/B978-0-12-800168-4.00006-8. PMID 24629188. ## External links[edit] Classification D * OMIM: 608161 153700 * MeSH: D057826 * DiseasesDB: 34190 * Vitelliform macular dystrophy at NLM Genetics Home Reference * Best's disease - eMedicine.com * GeneReviews/NCBI/NIH/UW entry on Best Vitelliform Macular Dystrophy * NCBI Genetic Testing Registry * v * t * e * Diseases of the human eye Adnexa Eyelid Inflammation * Stye * Chalazion * Blepharitis * Entropion * Ectropion * Lagophthalmos * Blepharochalasis * Ptosis * Blepharophimosis * Xanthelasma * Ankyloblepharon Eyelash * Trichiasis * Madarosis Lacrimal apparatus * Dacryoadenitis * Epiphora * Dacryocystitis * Xerophthalmia Orbit * Exophthalmos * Enophthalmos * Orbital cellulitis * Orbital lymphoma * Periorbital cellulitis Conjunctiva * Conjunctivitis * allergic * Pterygium * Pseudopterygium * Pinguecula * Subconjunctival hemorrhage Globe Fibrous tunic Sclera * Scleritis * Episcleritis Cornea * Keratitis * herpetic * acanthamoebic * fungal * Exposure * Photokeratitis * Corneal ulcer * Thygeson's superficial punctate keratopathy * Corneal dystrophy * Fuchs' * Meesmann * Corneal ectasia * Keratoconus * Pellucid marginal degeneration * Keratoglobus * Terrien's marginal degeneration * Post-LASIK ectasia * Keratoconjunctivitis * sicca * Corneal opacity * Corneal neovascularization * Kayser–Fleischer ring * Haab's striae * Arcus senilis * Band keratopathy Vascular tunic * Iris * Ciliary body * Uveitis * Intermediate uveitis * Hyphema * Rubeosis iridis * Persistent pupillary membrane * Iridodialysis * Synechia Choroid * Choroideremia * Choroiditis * Chorioretinitis Lens * Cataract * Congenital cataract * Childhood cataract * Aphakia * Ectopia lentis Retina * Retinitis * Chorioretinitis * Cytomegalovirus retinitis * Retinal detachment * Retinoschisis * Ocular ischemic syndrome / Central retinal vein occlusion * Central retinal artery occlusion * Branch retinal artery occlusion * Retinopathy * diabetic * hypertensive * Purtscher's * of prematurity * Bietti's crystalline dystrophy * Coats' disease * Sickle cell * Macular degeneration * Retinitis pigmentosa * Retinal haemorrhage * Central serous retinopathy * Macular edema * Epiretinal membrane (Macular pucker) * Vitelliform macular dystrophy * Leber's congenital amaurosis * Birdshot chorioretinopathy Other * Glaucoma / Ocular hypertension / Primary juvenile glaucoma * Floater * Leber's hereditary optic neuropathy * Red eye * Globe rupture * Keratomycosis * Phthisis bulbi * Persistent fetal vasculature / Persistent hyperplastic primary vitreous * Persistent tunica vasculosa lentis * Familial exudative vitreoretinopathy Pathways Optic nerve Optic disc * Optic neuritis * optic papillitis * Papilledema * Foster Kennedy syndrome * Optic atrophy * Optic disc drusen Optic neuropathy * Ischemic * anterior (AION) * posterior (PION) * Kjer's * Leber's hereditary * Toxic and nutritional Strabismus Extraocular muscles Binocular vision Accommodation Paralytic strabismus * Ophthalmoparesis * Chronic progressive external ophthalmoplegia * Kearns–Sayre syndrome palsies * Oculomotor (III) * Fourth-nerve (IV) * Sixth-nerve (VI) Other strabismus * Esotropia / Exotropia * Hypertropia * Heterophoria * Esophoria * Exophoria * Cyclotropia * Brown's syndrome * Duane syndrome Other binocular * Conjugate gaze palsy * Convergence insufficiency * Internuclear ophthalmoplegia * One and a half syndrome Refraction * Refractive error * Hyperopia * Myopia * Astigmatism * Anisometropia / Aniseikonia * Presbyopia Vision disorders Blindness * Amblyopia * Leber's congenital amaurosis * Diplopia * Scotoma * Color blindness * Achromatopsia * Dichromacy * Monochromacy * Nyctalopia * Oguchi disease * Blindness / Vision loss / Visual impairment Anopsia * Hemianopsia * binasal * bitemporal * homonymous * Quadrantanopia subjective * Asthenopia * Hemeralopia * Photophobia * Scintillating scotoma Pupil * Anisocoria * Argyll Robertson pupil * Marcus Gunn pupil * Adie syndrome * Miosis * Mydriasis * Cycloplegia * Parinaud's syndrome Other * Nystagmus * Childhood blindness Infections * Trachoma * Onchocerciasis * v * t * e Diseases of ion channels Calcium channel Voltage-gated * CACNA1A * Familial hemiplegic migraine 1 * Episodic ataxia 2 * Spinocerebellar ataxia type-6 * CACNA1C * Timothy syndrome * Brugada syndrome 3 * Long QT syndrome 8 * CACNA1F * Ocular albinism 2 * CSNB2A * CACNA1S * Hypokalemic periodic paralysis 1 * Thyrotoxic periodic paralysis 1 * CACNB2 * Brugada syndrome 4 Ligand gated * RYR1 * Malignant hyperthermia * Central core disease * RYR2 * CPVT1 * ARVD2 Sodium channel Voltage-gated * SCN1A * Familial hemiplegic migraine 3 * GEFS+ 2 * Febrile seizure 3A * SCN1B * Brugada syndrome 6 * GEFS+ 1 * SCN4A * Hypokalemic periodic paralysis 2 * Hyperkalemic periodic paralysis * Paramyotonia congenita * Potassium-aggravated myotonia * SCN4B * Long QT syndrome 10 * SCN5A * Brugada syndrome 1 * Long QT syndrome 3 * SCN9A * Erythromelalgia * Febrile seizure 3B * Paroxysmal extreme pain disorder * Congenital insensitivity to pain Constitutively active * SCNN1B/SCNN1G * Liddle's syndrome * SCNN1A/SCNN1B/SCNN1G * Pseudohypoaldosteronism 1AR Potassium channel Voltage-gated * KCNA1 * Episodic ataxia 1 * KCNA5 * Familial atrial fibrillation 7 * KCNC3 * Spinocerebellar ataxia type-13 * KCNE1 * Jervell and Lange-Nielsen syndrome * Long QT syndrome 5 * KCNE2 * Long QT syndrome 6 * KCNE3 * Brugada syndrome 5 * KCNH2 * Short QT syndrome * KCNQ1 * Jervell and Lange-Nielsen syndrome * Romano–Ward syndrome * Short QT syndrome * Long QT syndrome 1 * Familial atrial fibrillation 3 * KCNQ2 * BFNS1 Inward-rectifier * KCNJ1 * Bartter syndrome 2 * KCNJ2 * Andersen–Tawil syndrome * Long QT syndrome 7 * Short QT syndrome * KCNJ11 * TNDM3 * KCNJ18 * Thyrotoxic periodic paralysis 2 Chloride channel * CFTR * Cystic fibrosis * Congenital absence of the vas deferens * CLCN1 * Thomsen disease * Myotonia congenita * CLCN5 * Dent's disease * CLCN7 * Osteopetrosis A2, B4 * BEST1 * Vitelliform macular dystrophy * CLCNKB * Bartter syndrome 3 TRP channel * TRPC6 * FSGS2 * TRPML1 * Mucolipidosis type IV Connexin * GJA1 * Oculodentodigital dysplasia * Hallermann–Streiff syndrome * Hypoplastic left heart syndrome * GJB1 * Charcot–Marie–Tooth disease X1 * GJB2 * Keratitis–ichthyosis–deafness syndrome * Ichthyosis hystrix * Bart–Pumphrey syndrome * Vohwinkel syndrome) * GJB3/GJB4 * Erythrokeratodermia variabilis * Progressive symmetric erythrokeratodermia * GJB6 * Clouston's hidrotic ectodermal dysplasia Porin * AQP2 * Nephrogenic diabetes insipidus 2 See also: ion channels [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Vitelliform macular dystrophy	c0339510	28,538	wikipedia	https://en.wikipedia.org/wiki/Vitelliform_macular_dystrophy	2021-01-18T18:46:59	{"gard": ["182", "10120"], "mesh": ["D057826"], "umls": ["C0339510"], "orphanet": ["99000", "1243"], "wikidata": ["Q830265"]}
Not to be confused with Granuloma inguinale. Granuloma annulare Perforating form of Granuloma annulare on hand SpecialtyDermatology Granuloma annulare is a fairly rare, chronic skin condition which presents as reddish bumps on the skin arranged in a circle or ring.[1] It can initially occur at any age and is four times more common in females. ## Contents * 1 Signs and symptoms * 2 Causes * 3 Pathology * 4 Diagnosis * 4.1 Types * 5 Treatment * 6 History * 7 See also * 8 References * 9 External links ## Signs and symptoms[edit] Micrograph showing a palisaded granuloma in a case of granuloma annulare. H&E stain. Aside from the visible rash, granuloma annulare is usually asymptomatic. Sometimes the rash may burn or itch. People with granuloma annulare usually notice a ring of small, firm bumps (papules) over the backs of the forearms, hands or feet, often centered on joints or knuckles. The bumps are caused by the clustering of T cells below the skin. These papules start as very small, pimple looking bumps, which spread over time from that size to dime, quarter, half-dollar size and beyond. Occasionally, multiple rings may join into one. Rarely, granuloma annulare may appear as a firm nodule under the skin of the arms or legs. It also occurs on the sides and circumferential at the waist and without therapy can continue to be present for many years. Outbreaks continue to develop at the edges of the aging rings.[citation needed] ## Causes[edit] The condition is usually seen in otherwise healthy people. Occasionally, it may be associated with diabetes or thyroid disease. It has also been associated with auto-immune diseases such as systemic lupus erythematosus, rheumatoid arthritis, Lyme disease and Addison's disease. At this time, no conclusive connection has been made between patients.[citation needed] ## Pathology[edit] Granuloma annulare microscopically consists of dermal epithelioid histiocytes around a central zone of mucin—a so-called palisaded granuloma.[citation needed] ## Diagnosis[edit] ### Types[edit] Granuloma annulare may be divided into the following types:[2]:703–5 * Localized granuloma annulare * Generalized granuloma annulare * Patch-type granuloma annulare * Subcutaneous granuloma annulare * Perforating granuloma annulare ## Treatment[edit] Because granuloma annulare is usually asymptomatic and self-limiting with a course of about 2 years, initial treatment is generally topical steroids or calcineurin inhibitors; if unimproved with topical treatments, it may be treated with intradermal injections of steroids. If local treatment fails it may be treated with systemic corticosteroids.[3][4] Treatment success varies widely, with most patients finding only brief success with the above-mentioned treatments. New research out of India suggests that the combination of rifampin (600 mg), ofloxacin (400 mg), and minocycline hydrochloride (100 mg) once monthly, or ROM therapy, produces promising results.[5] Most lesions of granuloma annulare disappear in pre-pubertal patients with no treatment within two years while older patients (50+) have rings for upwards of 20 years. The appearance of new rings years later is not uncommon.[6] ## History[edit] The disease was first described in 1895 by Thomas Colcott Fox and it was named granuloma annulare by Henry Radcliffe Crocker in 1902.[7] ## See also[edit] * Granuloma * Necrobiosis lipoidica ## References[edit] 1. ^ Dennis, Mark; Bowen, William Talbot; Cho, Lucy (2012). "Granuloma annulare". Mechanisms of Clinical Signs. Elsevier. p. 525. ISBN 978-0729540759; pbk 2. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: Clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. 3. ^ http://www.buzzle.com/articles/granuloma-annulare-treatment.html 4. ^ https://www.dermnetnz.org/topics/granuloma-annulare/ 5. ^ Marcus, D. V.; Mahmoud, B. H.; Hamzavi, I. H. (2009). "Granuloma annulare treated with rifampin, ofloxacin, and minocycline combination therapy". Archives of Dermatology. 145 (7): 787–9. doi:10.1001/archdermatol.2009.55. PMID 19620560. 6. ^ "Granuloma Annulare: Treatment & Medication - March 14, 2007". 7. ^ Shanmuga1, Sekar C.; Rai1, Reena; Laila1, A.; Shanthakumari, S.; Sandhya, V. (2010), "Generalized granuloma annulare with tuberculoid granulomas: A rare histopathological variant", Indian Journal of Dermatology, Venereology and Leprology, 76 (1): 73–75, doi:10.4103/0378-6323.58691, PMID 20061743, retrieved 23 May 2010 ## External links[edit] * DermNet dermal-infiltrative/granuloma-annulare Classification D * ICD-10: L92.0 * ICD-9-CM: 695.89 * MeSH: D016460 * DiseasesDB: 5414 External resources * MedlinePlus: 000833 * eMedicine: derm/169 * v * t * e Diseases of the skin and appendages by morphology Growths Epidermal * Wart * Callus * Seborrheic keratosis * Acrochordon * Molluscum contagiosum * Actinic keratosis * Squamous-cell carcinoma * Basal-cell carcinoma * Merkel-cell carcinoma * Nevus sebaceous * Trichoepithelioma Pigmented * Freckles * Lentigo * Melasma * Nevus * Melanoma Dermal and subcutaneous * Epidermal inclusion cyst * Hemangioma * Dermatofibroma (benign fibrous histiocytoma) * Keloid * Lipoma * Neurofibroma * Xanthoma * Kaposi's sarcoma * Infantile digital fibromatosis * Granular cell tumor * Leiomyoma * Lymphangioma circumscriptum * Myxoid cyst Rashes With epidermal involvement Eczematous * Contact dermatitis * Atopic dermatitis * Seborrheic dermatitis * Stasis dermatitis * Lichen simplex chronicus * Darier's disease * Glucagonoma syndrome * Langerhans cell histiocytosis * Lichen sclerosus * Pemphigus foliaceus * Wiskott–Aldrich syndrome * Zinc deficiency Scaling * Psoriasis * Tinea (Corporis * Cruris * Pedis * Manuum * Faciei) * Pityriasis rosea * Secondary syphilis * Mycosis fungoides * Systemic lupus erythematosus * Pityriasis rubra pilaris * Parapsoriasis * Ichthyosis Blistering * Herpes simplex * Herpes zoster * Varicella * Bullous impetigo * Acute contact dermatitis * Pemphigus vulgaris * Bullous pemphigoid * Dermatitis herpetiformis * Porphyria cutanea tarda * Epidermolysis bullosa simplex Papular * Scabies * Insect bite reactions * Lichen planus * Miliaria * Keratosis pilaris * Lichen spinulosus * Transient acantholytic dermatosis * Lichen nitidus * Pityriasis lichenoides et varioliformis acuta Pustular * Acne vulgaris * Acne rosacea * Folliculitis * Impetigo * Candidiasis * Gonococcemia * Dermatophyte * Coccidioidomycosis * Subcorneal pustular dermatosis Hypopigmented * Tinea versicolor * Vitiligo * Pityriasis alba * Postinflammatory hyperpigmentation * Tuberous sclerosis * Idiopathic guttate hypomelanosis * Leprosy * Hypopigmented mycosis fungoides Without epidermal involvement Red Blanchable Erythema Generalized * Drug eruptions * Viral exanthems * Toxic erythema * Systemic lupus erythematosus Localized * Cellulitis * Abscess * Boil * Erythema nodosum * Carcinoid syndrome * Fixed drug eruption Specialized * Urticaria * Erythema (Multiforme * Migrans * Gyratum repens * Annulare centrifugum * Ab igne) Nonblanchable Purpura Macular * Thrombocytopenic purpura * Actinic/solar purpura Papular * Disseminated intravascular coagulation * Vasculitis Indurated * Scleroderma/morphea * Granuloma annulare * Lichen sclerosis et atrophicus * Necrobiosis lipoidica Miscellaneous disorders Ulcers * Hair * Telogen effluvium * Androgenic alopecia * Alopecia areata * Systemic lupus erythematosus * Tinea capitis * Loose anagen syndrome * Lichen planopilaris * Folliculitis decalvans * Acne keloidalis nuchae Nail * Onychomycosis * Psoriasis * Paronychia * Ingrown nail Mucous membrane * Aphthous stomatitis * Oral candidiasis * Lichen planus * Leukoplakia * Pemphigus vulgaris * Mucous membrane pemphigoid * Cicatricial pemphigoid * Herpesvirus * Coxsackievirus * Syphilis * Systemic histoplasmosis * Squamous-cell carcinoma * v * t * e Cutaneous keratosis, ulcer, atrophy, and necrobiosis Epidermal thickening * keratoderma: Keratoderma climactericum * Paraneoplastic keratoderma * Acrokeratosis paraneoplastica of Bazex * Aquagenic keratoderma * Drug-induced keratoderma * psoriasis * Keratoderma blennorrhagicum * keratosis: Seborrheic keratosis * Clonal seborrheic keratosis * Common seborrheic keratosis * Irritated seborrheic keratosis * Seborrheic keratosis with squamous atypia * Reticulated seborrheic keratosis * Dermatosis papulosa nigra * Keratosis punctata of the palmar creases * other hyperkeratosis: Acanthosis nigricans * Confluent and reticulated papillomatosis * Callus * Ichthyosis acquisita * Arsenical keratosis * Chronic scar keratosis * Hyperkeratosis lenticularis perstans * Hydrocarbon keratosis * Hyperkeratosis of the nipple and areola * Inverted follicular keratosis * Lichenoid keratosis * Multiple minute digitate hyperkeratosis * PUVA keratosis * Reactional keratosis * Stucco keratosis * Thermal keratosis * Viral keratosis * Warty dyskeratoma * Waxy keratosis of childhood * other hypertrophy: Keloid * Hypertrophic scar * Cutis verticis gyrata Necrobiosis/granuloma Necrobiotic/palisading * Granuloma annulare * Perforating * Generalized * Subcutaneous * Granuloma annulare in HIV disease * Localized granuloma annulare * Patch-type granuloma annulare * Necrobiosis lipoidica * Annular elastolytic giant-cell granuloma * Granuloma multiforme * Necrobiotic xanthogranuloma * Palisaded neutrophilic and granulomatous dermatitis * Rheumatoid nodulosis * Interstitial granulomatous dermatitis/Interstitial granulomatous drug reaction Foreign body granuloma * Beryllium granuloma * Mercury granuloma * Silica granuloma * Silicone granuloma * Zirconium granuloma * Soot tattoo * Tattoo * Carbon stain Other/ungrouped * eosinophilic dermatosis * Granuloma faciale Dermis/ localized CTD Cutaneous lupus erythematosus * chronic: Discoid * Panniculitis * subacute: Neonatal * ungrouped: Chilblain * Lupus erythematosus–lichen planus overlap syndrome * Tumid * Verrucous * Rowell's syndrome Scleroderma/ Morphea * Localized scleroderma * Localized morphea * Morphea–lichen sclerosus et atrophicus overlap * Generalized morphea * Atrophoderma of Pasini and Pierini * Pansclerotic morphea * Morphea profunda * Linear scleroderma Atrophic/ atrophoderma * Lichen sclerosus * Anetoderma * Schweninger–Buzzi anetoderma * Jadassohn–Pellizzari anetoderma * Atrophoderma of Pasini and Pierini * Acrodermatitis chronica atrophicans * Semicircular lipoatrophy * Follicular atrophoderma * Linear atrophoderma of Moulin Perforating * Kyrle disease * Reactive perforating collagenosis * Elastosis perforans serpiginosa * Perforating folliculitis * Acquired perforating dermatosis Skin ulcer * Pyoderma gangrenosum Other * Calcinosis cutis * Sclerodactyly * Poikiloderma vasculare atrophicans * Ainhum/Pseudo-ainhum [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Granuloma annulare	c0085074	28,539	wikipedia	https://en.wikipedia.org/wiki/Granuloma_annulare	2021-01-18T18:55:32	{"gard": ["6546"], "mesh": ["D016460"], "umls": ["C0085074"], "icd-9": ["695.89"], "wikidata": ["Q455085"]}
Hyperekplexia Other namesExaggerated Surprise, Exaggerated Startle Response, Startle Disease[1] Mutations of the neuroreceptor, Glycine receptor subunit alpha-1(GLRA1) can cause Hyperekplexia. Pronunciation * /ˌhaɪ.pɚ.ɛkˈplɛk.si.ə/ SpecialtyNeurology, Genetics SymptomsIncreased startle response to sudden auditory, visual, or tactile stimulation. ComplicationsIncreased alcohol & drug use. DurationChronic. CausesMutation of either the GLRA1 gene, GLRB gene, SLC6A5 gene, X-linked (ARHGEF9) gene, or GPHN gene.[2] Differential diagnosisJumping Frenchmen of Maine Syndrome MedicationClonazepam or phenobarbital, carbamazepine, 5-hydroxytryptophan, phenytoin, sodium valproate, diazepam, or piracetam[2] Frequency1 in 40,000[2] Hyperekplexia /ˌhaɪ.pɚ.ɛkˈplɛk.si.ə/ ("exaggerated surprise") is a very rare neurologic disorder classically characterised by pronounced startle responses to tactile or acoustic stimuli and hypertonia. The hypertonia may be predominantly truncal, attenuated during sleep and less prominent after a year of age. Classic hyperekplexia is caused by genetic mutations in a number of different genes, all of which play an important role in glycine neurotransmission. Glycine is used by the central nervous system as an inhibitory neurotransmitter. Hyperekplexia is generally classified as a genetic disease,[3] but some disorders can mimic the exaggerated startle of hyperekplexia.[4] ## Contents * 1 Signs and symptoms * 2 Genetics * 2.1 GLRA1 * 2.2 GLRB * 2.3 SLC6A5 * 2.4 GPHN * 2.5 ARHGEF9 * 3 Diagnosis * 4 Treatment * 5 History * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] The three main signs of hyperekplexia are generalized stiffness, excessive startle beginning at birth and nocturnal myoclonus.[5] Affected individuals are fully conscious during episodes of stiffness, which consist of forced closure of the eyes and an extension of the extremities followed by a period of generalised stiffness and uncontrolled falling at times.[6] Initially, the disease was classified into a "major" and a "minor" form, with the minor form being characterized by an excessive startle reflex, but lacking stiffness.[6] There is only genetic evidence for the existence of the major form.[6] Other signs and symptoms of hyperekplexia may include episodic neonatal apnea, excessive movement during sleep and the head-retraction reflex. The link to some cases of Sudden Infant Death remains controversial.[3] ## Genetics[edit] Hyperekplexia is known to be caused by a variety of genes, encoding both pre- and postsynaptic proteins. The symptoms displayed, as well as the forms of heritance, vary based on which gene is affected. ### GLRA1[edit] The first gene linked conclusively to hyperekplexia was GLRA1.[6] The GLRA1 gene encodes the glycine receptor alpha-1 subunit, which, together with the glycine receptor beta subunit, forms synaptic glycine receptors. Inhibitory glycine receptors are ligand-gated chloride channels that facilitate fast responses in the brainstem and spinal-cord. Homomeric glycine receptors composed exclusively of alpha-1 subunits exhibit normal ion channel electrophysiology but are not sequestered at the synaptic junction.[7] Native glycine receptors are thus supposed to be heteromers of the alpha-1 and beta subunits, in either a 3:2 or 2:3 ratio.[7] Within these heteromers, it is believed that the alpha-1 subunits bind glycine and undergo a conformational change, inducing a conformational change in the pentamer, causing the ion-channel to open. Although autosomal dominant[6] inheritance was initially reported, there are at least as many cases described with autosomal recessive inheritance.[8] Thus far, the general rule is that mutations causing structurally normal proteins that cannot bind glycine or cannot properly undergo a required conformational change will result in a dominant form of the disease, while mutations that result in truncated or wildly malformed subunits that cannot be integrated into a receptor protein will result in a recessive form.[8] ### GLRB[edit] The GLRB gene encodes the beta subunit of the glycine receptor. Homomeric glycine receptors composed of beta subunits do not open in response to glycine stimulation,[9] however, the beta subunit is essential for proper receptor localization through its interactions with gephyrin, which results in receptor clustering at the synaptic cleft.[10] As such, the defects within the GLRB gene show autosomal recessive inheritance.[11] ### SLC6A5[edit] The SLC6A5 gene encodes the GlyT2 transporter, a neuronal pre-synaptic glycine re-uptake transporter. In comparison to the GlyT1 transporter, found mostly in glial cells, GlyT2 helps maintain a high concentration of glycine within the axon terminal of glycinergic neurons.[12] Mutations of the SLC6A5 gene have been associated with hyperekplexia in an autosomal recessive manner.[13] Defects within this gene are hypothesized either to affect the incorporation of the transporter into the cellular membrane or to its affinity for the molecules it transports: sodium ions, chloride ions and glycine.[13] Any of these actions would drastically reduce the pre-synaptic cell's ability to produce the high vesicular concentrations of glycine necessary for proper glycine neurotransmission. GPHN and ARHGEF9 are often included in lists of genetic causes of hyperekplexia - but in fact they produce a much more complex phenotype, very distinct from classical hyperekplexia. As such they are no longer considered to be causative genes.[citation needed] ### GPHN[edit] Gephyrin, an integral membrane protein believed to coordinate glycine receptors, is coded by the gene GPHN. A heterozygous mutation in this gene has been identified in a sporadic case of hyperekplexia, though experimental data is inconclusive as to whether the mutation is pathogenic.[14] Gephyrin is essential for glycine receptor clustering at synaptic junctions through its action of binding both the glycine receptor beta subunit and internal cellular microtubule structures.[10] Gephyrin also assists in clustering GABA receptors at synapses and molybdenum cofactor synthesis.[15] Because of its multi-functional nature, it is not presumed to be a common genetic source of hyperekplexia.[14] ### ARHGEF9[edit] A defect within the gene coding for collybistin (ARHGEF9) has been shown to cause hyperekplexia in concert with epilepsy.[16] Since the ARHGEF9 gene is on the X chromosome, this gene displays X-linked recessive heritance. The collybistin protein is responsible for proper gephyrin targeting, which is crucial for the proper localization of glycine and GABA receptors. Deficiencies in collybistin function would result in an artificial lack of glycine and GABA receptors at the synaptic cleft.[16] ## Diagnosis[edit] There are three conditions used to diagnose if an infant has hereditary hyperekplexia: if the child's body is stiff all over as soon as they are born, if they overreact to noises and other stimuli, and if the reaction to stimuli is followed by an overall stiffness where the child is unable to make any voluntary movements.[17] A combination of electroencephalogram and an electromyogram may help diagnose this condition in patients who have not displayed symptoms as children. the electroencephalogram will not show abnormal activity other than a spike in wakefulness or alertness, while the electromyogram will show rapid muscular responses and hyperreflexia. Otherwise, genetic testing is the only definitive diagnosis.[17] MRIs and CT scans will be normal unless other conditions exist.[17] ## Treatment[edit] The most commonly effective treatment is clonazepam, which leads to the increased efficacy of another inhibitory neurotransmitter, GABA.[3] There are anecdotal reports of the use of levetiracetam in genetic and acquired hyperekplexia.[18] During attacks of hypertonia and apnea, the limbs and head may be flexed towards the trunk in order to dissipate the symptoms. This is named the Vigevano maneuver after the doctor who invented it.[19] ## History[edit] The disorder was first described in 1958 by Kirstein and Silfverskiold, who reported a family with 'drop seizures'.[20] In 1962 Drs. Kok and Bruyn reported an unidentified hereditary syndrome, initially started as hypertonia in infants.[21] Genetic analysis within this large Dutch pedigree was later found to carry a mutation within the GLRA1 gene, which was the first gene implicated in hyperekplexia.[6] ## See also[edit] * Jumping Frenchmen of Maine * Latah * Stiff person syndrome ## References[edit] 1. ^ Beers, Mark H. MD (2006). The Merck Manual (16th ed.). Whitehouse Station, NJ: Merck Research Laboratories. p. 1764. ISBN 0911910-18-2. 2. ^ a b c Kerkar, Pramod, M.D., FFARCSI, DA. "Exaggerated Startle Response: Causes, Symptoms, Treatment, Recovery, Yoga". PainAssist. PainAssist. Retrieved 19 May 2020. 3. ^ a b c Bakker MJ, van Dijk JG, van den Maagdenberg AM, Tijssen MA (2006-05-19). "Startle Syndromes". Lancet Neurology. 5 (6): 513–524. doi:10.1016/S1474-4422(06)70470-7. PMID 16713923. S2CID 24056686. 4. ^ van de Warrenburg, B. P. C.; C. Cordivari; P. Brown; K. P. Bhatia (2007-04-05). "Persisting Hyperekplexia After Idiopathic, Self-Limiting Brainstem Encephalopathy". Movement Disorders. 22 (7): 1017–20. doi:10.1002/mds.21411. PMID 17415799. 5. ^ Koning-Tijssen, M.A.J.; O.F. Brouwer (2000-04-27). "Hyperekplexia in the Neonate". Movement Disorders. 15 (6): 1293–6. doi:10.1002/1531-8257(200011)15:6<1293::aid-mds1047>3.0.co;2-k. PMID 11104232. 6. ^ a b c d e f Tijssen, M.A.J.; R. Shiang; J. van Deutekom; R. H. Boerman; J. Wasmuth; L. A. Sandkuijl; R. R. Frants; G. W. Padberg (1995-06-01). "Molecular Genetic Reevaluation of the Dutch Hyperekplexia Family" (PDF). Archives of Neurology. 52 (6): 578–582. doi:10.1001/archneur.1995.00540300052012. hdl:2066/20657. PMID 7763205. 7. ^ a b Lynch, J. W. (2008-08-03). "Native glycine receptor subtypes and their physiological roles". Neuropharmacology. 56 (1): 303–9. doi:10.1016/j.neuropharm.2008.07.034. PMID 18721822. S2CID 43613876. 8. ^ a b Villmann C, Oertel J, Melzer N, Becker CM (2009). "Recessive hyperekplexia mutations of the glycine receptor [alpha]-1 subunit affect cell surface integration and stability". Journal of Neurochemistry. 111 (3): 837–847. doi:10.1111/j.1471-4159.2009.06372.x. PMID 19732286. 9. ^ Bormann, J.; N. Rundstrom; H. Betz; D. Langosch (1993). "Residues within transmembrane segment M2 determine chloride conductance of glycine receptor homo- and hetero-oligomers". EMBO Journal. 12 (10): 3729–37. doi:10.1002/j.1460-2075.1993.tb06050.x. PMC 413654. PMID 8404844. 10. ^ a b Meyer, G.; J. Kirsch; H. Betz; D. Langosch (1995). "Identification of a Gephyrin Binding Motif on the Glycine Receptor Beta Subunit". Neuron. 15 (3): 563–572. doi:10.1016/0896-6273(95)90145-0. PMID 7546736. S2CID 10164739. 11. ^ Rees, M. I.; T. M. Lewis; J. B. Kwok; G. R. Mortier; P. Govaert; R. G. Snell; P. R. Schofield; M. J. Owen (2002-04-01). "Hyperekplexia associated with compound heterozygote mutations in the beta-subunit of the human inhibitory glycine receptor (GLRB)". Human Molecular Genetics. 11 (7): 853–860. doi:10.1093/hmg/11.7.853. PMID 11929858. 12. ^ Rousseau, F.; K. R. Aubrey; S. Supplisson (2008-09-24). "The Glycine Transporter GlyT2 Controls the Dynamics of Synaptic Vesicle Refilling in Inhibitory Spinal Cord Neurons". Journal of Neuroscience. 28 (39): 9755–68. doi:10.1523/JNEUROSCI.0509-08.2008. PMC 6671229. PMID 18815261. 13. ^ a b Rees MI, Harvey K, Pearce BR, Chung SK, Duguid IC, Thomas P, Beatty S, Graham GE, Armstrong L, Shiang R, Abbott KJ, Zuberi SM, Stephenson JB, Owen MJ, Tijssen MA, van den Maagdenberg AM, Smart TG, Supplisson S, Harvey RJ (2006). "Mutations in the gene encoding GlyT2 (SLC6A5) define a presynaptic component of human startle disease". Nature Genetics. 38 (7): 801–806. doi:10.1038/ng1814. PMC 3204411. PMID 16751771. 14. ^ a b Rees MI, Harvey K, Ward H, White JH, Evans L, Duguid IC, Hsu CC, Coleman SL, Miller J, Baer K, Waldvogel HJ, Gibbon F, Smart TG, Owen MJ, Harvey RJ, Snell RG (2003-04-08). "Isoform Heterogeneity of the Human Gephyrin Gene (GPHN), Binding Domains to the Glycine Receptor, and Mutation Analysis in Hyperekplexia". Journal of Biological Chemistry. 278 (27): 24688–96. doi:10.1074/jbc.M301070200. PMID 12684523. 15. ^ Fritschy, J.-M.; R. J. Harvey; G. Schwarz (2008). "Gephyrin: where do we stand, where do we go?". Trends in Neurosciences. 31 (5): 257–264. doi:10.1016/j.tins.2008.02.006. PMID 18403029. S2CID 6885626. 16. ^ a b Harvey K, Duguid IC, Alldred MJ, Beatty SE, Ward H, Keep NH, Lingenfelter SE, Pearce BR, Lundgren J, Owen MJ, Smart TG, Lüscher B, Rees MI, Harvey RJ (2004). "The GDP-GTP Exchange Factor Collybistin: An Essential Determinant of Neuronal Gephyrin Clustering" (PDF). Journal of Neuroscience. 24 (25): 5816–26. doi:10.1523/JNEUROSCI.1184-04.2004. PMC 6729214. PMID 15215304. 17. ^ a b c Tijssen, Marina A.J.; Rees, Mark I. (1993). "Hyperekplexia". In Adam, Margaret P.; Ardinger, Holly H.; Pagon, Roberta A.; Wallace, Stephanie E.; Bean, Lora J.H.; Stephens, Karen; Amemiya, Anne (eds.). GeneReviews®. Seattle (WA): University of Washington, Seattle. PMID 20301437. 18. ^ Luef, G. J.; W. N. Loescher (June 2007). "The effect of levetiracetam in startle disease". Journal of Neurology. 254 (6): 808–9. doi:10.1007/s00415-006-0437-z. PMID 17401745. S2CID 358799. 19. ^ Vigevano, F.; M. Di Capua; B. Dalla Bernardina (1989). "Startle disease: an avoidable cause of sudden infant death". Lancet. 1 (8631): 216. doi:10.1016/s0140-6736(89)91226-9. PMID 2563117. S2CID 32077413. 20. ^ Kirstein, L.; B. P. Silfverskiold (1958). "A Family with Emotionally Precipitated Drop Seizures". Acta Psychiatrica et Neurologica. 33 (4): 471–6. doi:10.1111/j.1600-0447.1958.tb03533.x. PMID 13594585. S2CID 143799581. 21. ^ Kok, O.; G. W. Bruyn (1962). "An Unidentified Hereditary Disease". Lancet. 279 (7243): 1359. doi:10.1016/S0140-6736(62)92475-3. ## External links[edit] * GeneReview/NIH/UW entry on Hyperekplexia Classification D * ICD-10: G25.8 * ICD-9-CM: 759.89 * OMIM: 149400 138491 138492 300429 300607 603930 604159 * MeSH: D000071017 * DiseasesDB: 7208 External resources * GeneReviews: Hyperekplexia * Orphanet: 306773 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Hyperekplexia	c1835614	28,540	wikipedia	https://en.wikipedia.org/wiki/Hyperekplexia	2021-01-18T19:02:46	{"gard": ["3129"], "mesh": ["C538136"], "icd-9": ["759.89"], "orphanet": ["306773", "3197"], "synonyms": [], "wikidata": ["Q1781802"]}
Epiphysiolysis of the hip is a rare osteonecrosis disorder characterized by unilateral or bilateral disruption of the capital femoral physis with varying degrees of posterior epiphysis translation and simultaneous anterior metaphysis displacement. Patients typically present in pre-adolescence/adolescence with pain of variable intensity in varying locations (hip, groin, thigh, knee). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Epiphysiolysis of the hip	c0149887	28,541	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=399329	2021-01-23T18:41:13	{"mesh": ["D060048"], "icd-10": ["M93.9"], "synonyms": ["Epiphysiolysis of the upper femur", "Femoral head epiphysiolysis", "SCFE", "SUFE", "Slipped capital femoral epiphysis", "Slipped upper femoral epiphysis"]}
Trisomy 4p is a rare chromosomal anomaly syndrome, resulting from the partial duplication of the short arm of chromosome 4, with a highly variable phenotype, typically characterized by pre- and postnatal growth delay, psychomotor developmental delay and craniofacial dysmorphism (microcephaly, prominent glabelle, hypertelorism, enlarged ears with abnormal helix and antihelix, bulbous nose with flat or depressed nasal bridge, long philtrum, retrognathia with pointed chin). Additional features include skeletal (rocker bottom feet, arachnodactyly, camptodactyly) and renal malformations, cardiac defects, ocular abnormalities and abnormal genitalia in males. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Trisomy 4p	c2931571	28,542	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1738	2021-01-23T17:45:41	{"gard": ["6091"], "mesh": ["C537643"], "umls": ["C2931570", "C2931571"], "icd-10": ["Q92.2"], "synonyms": ["Duplication 4p", "Duplication of the short arm of chromosome 4", "Trisomy of the short arm of chromosome 4"]}
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. (April 2019) This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Chronic airway-digestive inflammatory disease" – news · newspapers · books · scholar · JSTOR (February 2007) (Learn how and when to remove this template message) Chronic airway-digestive inflammatory disease SpecialtyGastroenterology Sinus disease, allergies, and asthma have been shown to be intimately related through recent research[citation needed]. Moreover, gastroesophageal reflux disease (GERD), laryngopharyngeal reflux disease (LPRD) and/or snoring or sleep apnea are often present as well. “Chronic Airway-Digestive Inflammatory Disease” (CAID) is a phrase which has been coined by Dr. Jordan S. Josephson, M.D., F.A.C.S. and Dr. Jens Ponikeau, M.D. to describe this very complex set of problems which are caused by inflammation. This term was first described in a book entitled Sinus Relief Now.[1] CAID directly affects the upper respiratory system (the nose and the sinuses), the lower airway (the lungs) and the GI tract and these areas are intimately connected. CAID begins when bacteria, virus, fungus (mold), pollutants or other irritants, or an allergen initiate an inflammatory response in the airway (both upper and lower). Inflammatory responses may then lead to a number of related reactions. For example, allergies often worsen sinus problems, and sinus problems and allergies can trigger or worsen asthma. Reflux can be set off by sinus problems and reflux can also send acids up to the upper airway and worsen the inflammation already occurring secondary to infection. Inflammation in these different areas are all related and the reaction can cause the symptoms to worsen in a vicious cycle. CAID can also impact organs beyond the respiratory (breathing) and digestive systems. Heart disease, stroke, infertility, painful headaches and chronic fatigue syndrome may be linked to CAID. CAID must first be diagnosed before each of these conditions can be properly treated. Available treatment options include over the counter remedies, holistic medicines and allopathic treatments, prescription medications, surgery and lifestyle changes. Unfortunately, CAID is a chronic disease, which is not cured by medicines and/or surgery but definitely can be controlled with good comprehensive care. However, symptoms may be controlled and unnecessary pain alleviated. One treatment option is the so-called Five Part Plan for treatment described in the book Sinus Relief Now which includes: Using irrigation to care for sinuses, Managing the level of mould, allergens, and other pollutants in homes, offices, and cars, by cleaning up your environment Knowing which foods trigger CAID symptoms, and removing them from your diet Being compliant with your treatment. Both Eastern Alternative and Western Traditional Medicine Treatments complement each other and should be investigated to provide a comprehensive holistic approach. Embracing life-altering changes to enjoy your health (ie. smoking cessation). ## References[edit] 1. ^ Josephson, Jordan S. (2006). Sinus Relief Now. Perigee Trade. 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Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Chronic airway-digestive inflammatory disease	None	28,543	wikipedia	https://en.wikipedia.org/wiki/Chronic_airway-digestive_inflammatory_disease	2021-01-18T18:47:34	{"wikidata": ["Q55647711"]}
The central odontogenic fibroma is a rare benign odontogenic tumor. It is more common in adults, with the average age being 40. It is twice as likely to affect women than men. It is usually found either in the anterior maxilla or the posterior mandible. Radiographically it presents with either radiolucency or mixed radiolucency/opaque. The simple type is characterized by delicate fibrillar stroma of collagen containing fibroblasts; the WHO type is characterized by more mature fibrillar stroma of collagen. Treatment is by surgical removal ## References[edit] * Kahn, Michael A. Basic Oral and Maxillofacial Pathology. Volume 1. 2001. This article about a neoplasm is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Central odontogenic fibroma	c1260966	28,544	wikipedia	https://en.wikipedia.org/wiki/Central_odontogenic_fibroma	2021-01-18T18:49:15	{"umls": ["C1260966"], "wikidata": ["Q16858684"]}
Impairments primarily associated with cannabis use Amotivational syndrome SpecialtyPsychology Amotivational syndrome is a chronic psychiatric disorder characterized by signs that are linked to cognitive and emotional states such as detachment, blunted emotion and drives, executive functions like memory and attention,[1] disinterest, passivity, apathy, and a general lack of motivation.[2][3] This syndrome can be branched into two subtypes - marijuana amotivational syndrome, interchangeably known as cannabis induced amotivational syndrome which is caused by usage and/or dependency of the substance and is primarily associated with long-term effects of cannabis use,[1] and SSRI-induced amotivational syndrome or SSRI-induced apathy caused by the intake of SSRI medication dosage.[4][5] According to the Handbook of Clinical Psychopharmacology for Therapists, amotivational syndrome is listed as a possible side effect of SSRIs in the treatment of clinical depression. [6] ## Contents * 1 Signs & Symptoms * 2 Subtypes * 2.1 Cannabis Amotivational Syndrome * 2.2 SSRI-Induced Amotivational Syndrome * 3 Treatment & Measurement * 3.1 Cannabis Amotivational Syndrome * 3.2 SSRI-Induced Amotivational Syndrome * 4 Current Research & Discourse * 4.1 Cannabis Amotivational Syndrome * 4.2 SSRI-Induced Amotivational Syndrome * 5 See also * 6 References ## Signs & Symptoms[edit] Amotivational syndrome has been suspected to affect the frontal cortex or frontal lobe of the brain by the impairment of that region[7] which monitors cognitive functions and skills that revolve around emotional expression, decision making, prioritisation, and internal, purposeful mental action. It is most often detected through signs that are linked to apathy such as disinhibited presentations, short and long term memory deficit or amnesia, a lack of emotional display also known as emotional blunting, relative disinterest, passivity, and reluctance to participate in prolonged activities that require attention or tenacity.[2][3][5] Common symptoms that may also be experienced include incoherence, an inability to concentrate on tasks, emotional distress, a diminished level of consciousness, selective attention or attentional control, and being withdrawn and asocial.[2][7] These symptoms are also generally linked to cannabis consumption and abuse, as well as SSRI medication that are often used as forms of antidepressant medication. ## Subtypes[edit] ### Cannabis Amotivational Syndrome[edit] Legal cannabis (marijuana) product. Overconsumption and reliance could lead to cannabis-induced amotivational syndrome. The term amotivational syndrome was first devised to understand and explain the diminished drive and desire to work or compete among the population of youth who are frequent consumers of cannabis and has since been researched through various methodological studies with this focus on cannabis, or marijuana.[4] Cannabis amotivational syndrome is often used interchangeably with marijuana amotivational syndrome and marijuana or cannabis induced or related amotivational syndrome. Cannabis related amotivational syndrome is closely tied with cannabis use disorder which is recognized in the fifth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and has similar conditions such as withdrawing and giving up from daily activities and neglecting major roles and responsibilities. It is one of the major complications of chronic exposure to cannabis as it includes the effects and elements of cognitive deficit or cognitive impairment that are similar to what appears in schizophrenia and depression. It is characterized by a gradual detachment and disconnect from the outer world due to a loss of emotional reactivity, drives, and aims. Responsiveness to any stimuli is limited, and those affected are unable to experience or anticipate any pleasure except through the use of cannabis. [1] Marijuana amotivational syndrome has been looked at within the context of how motivation-related constructs influence the young adult in the context of the school or workplace [4] as those affected have poor levels of school-related functioning, are unable to focus on schoolwork due to their lack of motivation, are less satisfied with participating in educational activities, and easily enter into conflict with scholastic authorities.[1] Additionally, marijuana amotivational syndrome is closely linked to self-efficacy, a psychological concept which encapsulates how one values their capabilities and the amount of confidence they hold in their capabilities to persevere - this is related to motivation as people who hold a high amount of self-efficacy are more likely to make efforts to complete a task and persist longer in those efforts compared to those with lower self-efficacy. ### SSRI-Induced Amotivational Syndrome[edit] Dopamine-Serotonin system that explains brain activity in relation to serotonergic pathways. Amotivational syndrome caused or related to SSRI dosage is also commonly known as apathy syndrome, SSRI-induced apathy syndrome, SSRI-induced apathy, and antidepressant apathy syndrome. . “Apathy is defined as the presence of diminished motivation in an individual - a development that is not attributable to a reduced level of consciousness, cognitive impairment (e.g., dementia), or emotional distress (i.e., depression)”.[5] This syndrome is linked to the consumption and dosage of selective serotonin reuptake inhibitors (SSRIs), which are typically used as antidepressants, and has been reported in patients undergoing SSRI treatment as SSRIs may modulate and alter the activity occurring in the frontal lobe of the brain,[2] one of the four major lobes in the brain that contains most of the dopaminergic pathways that are associated with reward, attention, short-term memory tasks, planning, and motivation. This syndrome may be related to serotonergic effects on the frontal lobes and/or serotonergic modulation of mid-brain dopaminergic systems which project to the prefrontal cortex, both suggesting the possibility of frontal lobe dysfunction due to the alteration of serotonin levels.[5] This brings on a number of similar symptoms that lead to dose dependency and apathy, however, it has often been unrecognized and undiagnosed due to the lack of prevalent data and its subtle and delayed onset.[2] When looking at SSRI-induced amotivational syndrome as a clinical side effect, it can be looked at through a behavioural perspective as well as an emotional perspective.[5] When looked at as a behavioural syndrome the association between apathy or low motivation and SSRI prescription has been recognized as a potential side effect, for example, behavioural apathy has been noted in several case reports.[5] Aside from a behavioural perspective, an emotional perspective emphasizes the emotional aspects of indifference such as a lack of emotional responsiveness, a reduction in emotional sensitivity such as numbing or blunting emotion, affected patients often describe having a restricted range of emotions including those emotions that are a part of everyday life, and distinct emotional themes in affected patience that include a general reduction in the intensity or experience of all emotions, both positive and negative, and feeling emotionally detached and “just not caring”, diminishing emotionality in both personal and professional interpersonal relationships . [5] ## Treatment & Measurement[edit] ### Cannabis Amotivational Syndrome[edit] Treatment of cannabis amotivational syndrome is like the treatment for cannabis dependence in which there should be careful evaluation for any signs of depression that predate the development of the amotivational syndrome and may be the basis for cannabis dependence and usage. [8] The user is slowly weaned off usage through urine monitoring, self-help groups, education, and therapy in different treatment settings such as group, family, and individual therapy [8] in order to separate themself from cannabis consumption and any cannabis-related environment as both contribute to the cognitive aspects of amotivational syndrome. [1] ### SSRI-Induced Amotivational Syndrome[edit] The treatment of SSRI-induced amotivational syndrome can often include educating the patient of symptoms and monitoring their symptoms with follow-up visits to check for the need to augment their SSRI dosage.[citation needed] Treatment is mainly focused on changing the dosage by reducing dosage, changing the medication class,[2] or discontinuing the use of the medication altogether. [5] ## Current Research & Discourse[edit] ### Cannabis Amotivational Syndrome[edit] Though there is a prevalent relationship between cannabis consumption and amotivational syndrome, there is still some considerable debate that exists around cannabis consumption causing amotivational syndrome meaning that it may not be a single entity but rather a collection of behaviors that form the result of a combination of effects of an already existent or reactive depression that occurs alongside cannabis’s ability to facilitate a unique attention state. [9] Trait absorption is often mentioned within discourses surrounding cannabis-induced amotivational syndrome and it states that the traits associated with a large majority of marijuana users, which are similar to traits found in those who have amotivational syndrome, such as boredom and a general feeling of disconnect, are absorbed and taken up by the cannabis user. [9] It is used as a common argument against cannabis potentially being able to cause amotivational syndrome, instead, many cannabis users have stated that users often absorb what is often thought of as the typical set of traits marijuana consumers possess, which overlap with some of the traits found in amotivational syndrome. [9] As a result, many have proposed that rather than cannabis being thought of as a psychologically harmful substance, it is instead thought of as an active placebo in which its effects on the mind are placebo effects in response to minimal physiological action rather than being a direct cause of the psychological changes seen in users. [9] Additionally, though research has been conducted, it is recognized that there is not enough substantial empirical research to conclude that the use of cannabis leads to amotivational syndrome. Anecdotal information such as statements taken from cannabis users includes feeling listless and lethargic. [10]Amotivational syndrome still ranks high among the key problems associated with the drug, with researchers having adopted the phrase “amotivational” to describe lethargic cannabis users. The US Department of Health and Human Services also warns that usage in youth may result in amotivational symptoms such as an apathetic approach to life, fatigue, and poor academic and work performance. [10] However, empirical research on the effects of cannabis on users’ motivation implies that there is no strong correlation and that there are numerous alternative explanations of these negative outcomes as a review of laboratory performance research, education data, and employment statistics fail to offer consistent evidence that directly link cannabis to any symptoms associated with amotivational syndrome. [10] Though several studies contain data in which heavy cannabis users have reported feeling a lack of motivation, it has also been acknowledged that other variables such as comorbid drug use and baselines for low motivation may not be examined. [10] ### SSRI-Induced Amotivational Syndrome[edit] Neuroimaging of lesions in the basal ganglia Most research in psychological fields regarding amotivational syndrome caused by SSRI treatment has revolved around case studies and anecdotal reports to understand how SSRI medication influences levels of motivation and apathy in patients. [11] There is considerable overlap in the clinical presentations of apathy and motivation and depression. Many patients with amotivational or apathy syndrome reported that they felt a lack of motivation that was unlike what they had sometimes experienced during previous episodes or depression, or that their feelings of apathy had no link to depression. Apathy syndrome has also been reported in a number of patients that have received or are receiving selective serotonin reuptake inhibitor (SSRI) treatment over the last decade, which has also been linked to a deficit in the performance and activities of daily living, signaling a functional decline. [11] It is a common behavioural problem that often goes undiagnosed and untreated, which is why it is considered to be clinical significant. Neuropsychological research has shown that a common feature of amotivational syndrome involves the presence of lesions and other abnormalities in the circulation of the frontal lobe. [11] Neuroimaging studies of clinical populations have also reported correlations between apathy and structural and functional changes in the frontal lobe in the anterior cingulate gyrus and subregions of the basal ganglia. [11] Recent case-control studies have also reported that apathy has appeared to be greater in patients who were treated with SSRI medication compared to patients who were not. [11] Current findings are consistent with other findings supporting the correlation of SSRI and apathy due to the occurrence of abnormalities found within various regions of the frontal lobe. [11] Though amotivational syndrome has been an emerging concern for pharmacotherapeutic industries to consider, there is still a growing body of empirical investigations that need to continue in order for the development of novel therapeutic interventions to improve, as well as treatment. [11] Currently, empirical studies are limited and there is not a substantial enough amount of research to fully understand the link between frontal lobe abnormalities caused by SSRIs and thus resulting in amotivational syndrome. There is a lack of large-scale clinical studies that focus on the prevalence of SSRI-induced amotivational syndrome with regards to emotional blunting and apathy in both psychiatric or primary care populations, despite the high prescription rates for SSRI medication. [5] There are also no current clinically popular scales to measure and assess SSRI-induced apathy. The Oxford Questionnaire of Emotional Side Effects of Antidepressants (OQESA) is a scale under development and presents a 26-item, Likert-style, self-report scale that aims to understand respondents’ emotional experiences such as a general reduction in emotions, a reduction in positive emotions, emotional detachment and blunting, and feelings of not caring. [5] Respondents are also asked to what extent they believe their antidepressant is responsible for these emotional symptoms. [5] ## See also[edit] * Cannabis portal * Avolition * Effects of cannabis ## References[edit] 1. ^ a b c d e Rovai, L; Maremmani, AG; Pacini, M; Pani, PP; Rugani, F; Lamanna, F; Schiavi, E; Mautone, S; Dell'Osso, L; Maremmani, I (2013). "Negative dimension in psychiatry. Amotivational syndrome as a paradigm of negative symptoms in substance abuse". Rivista di Psichiatria. 48 (1): 1–9. doi:10.1708/1228.13610. PMID 23438696. 2. ^ a b c d e f Garland, E. Jane; Baerg, Elizabeth A. (2001-06-01). "Amotivational Syndrome Associated with Selective Serotonin Reuptake Inhibitors in Children and Adolescents". Journal of Child and Adolescent Psychopharmacology. 11 (2): 181–186. doi:10.1089/104454601750284090. ISSN 1044-5463. PMID 11436958. 3. ^ a b Castaño, Guillermo A.; Becoña, Elisardo; Restrepo, Sandra Milena; Scoppetta, Orlando (2020-04-01). "Toward the Design and Validation of a Scale to Assess Amotivational Syndrome in Chronic Marijuana Users (ESATHC)". International Journal of Mental Health and Addiction. 18 (2): 305–313. doi:10.1007/s11469-019-00132-y. ISSN 1557-1882. S2CID 207990165. 4. ^ a b c Lac, Andrew; Luk, Jeremy W. (2018-02-01). "Testing the Amotivational Syndrome: Marijuana Use Longitudinally Predicts Lower Self-Efficacy Even After Controlling for Demographics, Personality, and Alcohol and Cigarette Use". Prevention Science. 19 (2): 117–126. doi:10.1007/s11121-017-0811-3. ISSN 1573-6695. PMC 5732901. PMID 28620722. 5. ^ a b c d e f g h i j k Sansone, Randy A.; Sansone, Lori A. (October 2010). "SSRI-Induced Indifference". Psychiatry (Edgmont). 7 (10): 14–18. ISSN 1550-5952. PMC 2989833. PMID 21103140. 6. ^ Preston, John; John, O'Neal; Mary, Talaga (2013). Handbook of Clinical Psychopharmacology for Therapists (7th ed.). New Harbinger Publications. p. 193. ISBN 978-1608826643. 7. ^ a b OZAKI, Shigeru; WADA, Kiyoshi (2001). "New Developments in Drug Dependence Studies. Amotivational syndrome in organic solvent abusers". Folia Pharmacologica Japonica. 117 (1): 42–48. doi:10.1254/fpj.117.42. ISSN 0015-5691. 8. ^ a b Schnoll, Sidney H.; Daghestani, Amin N. (1986-04-01). "Treatment of Marijuana Abuse". Psychiatric Annals. 16 (4): 249–254. doi:10.3928/0048-5713-19860401-12. ISSN 0048-5713. 9. ^ a b c d "UKCIA Research Library". www.ukcia.org. Retrieved 2020-11-18. 10. ^ a b c d Barnwell, Sara Smucker; Earleywine, Mitch; Wilcox, Rand (2006-01-12). "Cannabis, motivation, and life satisfaction in an internet sample". Substance Abuse Treatment, Prevention, and Policy. 1 (1): 2. doi:10.1186/1747-597X-1-2. ISSN 1747-597X. PMC 1435998. PMID 16722561. 11. ^ a b c d e f g Kim, Hye-Geum (March 6, 2019). "Apathy syndrome in a patient previously treated with selective serotonin reuptake inhibitors for depression". Yeungnam University Journal of Medicine. 36 (3): 249–253. doi:10.12701/yujm.2019.00150. PMC 6784646. 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Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Amotivational syndrome	None	28,545	wikipedia	https://en.wikipedia.org/wiki/Amotivational_syndrome	2021-01-18T19:10:04	{"wikidata": ["Q2914153"]}
Ellis et al. (1996) described 3 female sibs (1 a fetus) with multiple congenital anomalies; one liveborn sib died at 16 days of age and the other at 13 months. All 3 had microcephaly and cardiovascular defects (arterial truncus in one, ventricular septal defects in the others). Unilateral renal agenesis was found in the 2 infants, and hypolobulation of lungs was found in an infant and the fetus. Each of the sisters had at least one of the following features: cleft palate, preauricular pits, hypoplastic alae nasi, hydranencephaly, neck webbing, and short terminal phalanges of fingers. Wolf-Hirschhorn (194190) and Smith-Lemli-Opitz (270400) syndromes were excluded by cytogenetic, molecular, and biochemical studies. Ellis et al. (1996) considered this complex to be a 'new' syndrome with presumably autosomal recessive inheritance. Limbs \- Short terminal phalanges of fingers Neuro \- Hydranencephaly Neck \- Webbed neck Inheritance \- Autosomal recessive GU \- Unilateral renal agenesis Nose \- Hypoplastic alae nasi Ears \- Preauricular pits Head \- Microcephaly Lung \- Hypolobulation of lungs Cardiac \- Truncus arteriosus \- Ventricular septal defect Mouth \- Cleft palate ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	MICROCEPHALY, CONGENITAL HEART DISEASE, UNILATERAL RENAL AGENESIS, AND HYPOSEGMENTED LUNGS	c2931129	28,546	omim	https://www.omim.org/entry/601355	2019-09-22T16:14:58	{"mesh": ["C536205"], "omim": ["601355"], "orphanet": ["2516"]}
A rare genetic, neuro-ophthalmological disease characterized by progressive weakness of the external eye muscles, resulting in bilateral ptosis and diffuse symmetric ophthalmoparesis. Additional signs may include skeletal muscle weakness, cataracts, hearing loss, sensory axonal neuropathy, ataxia, parkinsonism, cardiomyopathy, hypogonadism and depression. It is usually less severe than autosomal recessive form. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Autosomal dominant progressive external ophthalmoplegia	c1834846	28,547	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=254892	2021-01-23T18:21:30	{"mesh": ["C563575"], "omim": ["157640", "609283", "609286", "610131", "613077"], "icd-10": ["H49.4"], "synonyms": ["adPEO"]}
A number sign (#) is used with this entry because retinitis pigmentosa-60 (RP60) can be caused by heterozygous mutation in the PRPF6 gene (613979) on chromosome 20q13.33. For a general phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000. Clinical Features Tanackovic et al. (2011) described the proband from a 4-generation family of European descent segregating autosomal dominant retinitis pigmentosa, who presented at 37 years of age for evaluation of decreased night vision and loss of peripheral vision. Funduscopy revealed bilateral normal discs with atrophy just temporal to the disc, clear macula, attenuated retinal arterioles, and bone spicule pigment all around the periphery. Reexamination almost 20 years later at 55 years of age demonstrated progression of disease, with decline in visual acuity to hand motions OD and 20/100 OS, as well as reductions in visual fields and full-field ERG amplitudes; funduscopy at that time showed waxy pallor of the discs bilaterally, atrophy of the retinal pigment epithelium and prominent choroidal vessels in each macula, attenuated retinal vessels, and bone spicule pigment visible in the midperiphery. An affected brother was diagnosed with RP at 16 years of age when he was evaluated for reduced night vision. He reported loss of peripheral vision at around 40 years of age. Although he was 2 years younger than the proband, his vision was always worse than that of his brother and gradually decreased to light perception only in both eyes by age 54 years. Molecular Genetics In 188 probands from families segregating autosomal dominant retinitis pigmentosa, Tanackovic et al. (2011) screened the candidate gene PRPF6 and identified a heterozygous missense mutation in 1 proband (613979.0001). The mutation was also detected in heterozygosity in his affected brother but was not found in 1,078 ethnically matched control chromosomes. Tanackovic et al. (2011) stated that PRPF6 was the sixth gene involved in pre-mRNA splicing and autosomal dominant RP, corroborating the hypothesis that deficiencies in the spliceosome play an important role in the molecular pathology of the disease. INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Reduced night vision \- Reduced peripheral vision \- Reduced visual acuity \- Waxy pallor of optic discs \- Atrophy of retinal pigment epithelium \- Attenuation of retinal vessels \- Bone spicule pigment in periphery MOLECULAR BASIS \- Caused by mutation in the pre-mRNA processing factor 6 gene (PRPF6, 613979.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	RETINITIS PIGMENTOSA 60	c0035334	28,548	omim	https://www.omim.org/entry/613983	2019-09-22T15:56:56	{"doid": ["0110411"], "mesh": ["D012174"], "omim": ["613983"], "orphanet": ["791"], "genereviews": ["NBK1417"]}
A rare ARX-related epileptic encephalopathy characterized by infantile onset of myoclonic epilepsy with generalized spasticity, severe global developmental delay, and moderate to profound intellectual disability. Obligate female carriers show subtle, generalized hyperreflexia. Late onset progressive spastic ataxia has also been reported. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	X-linked spasticity-intellectual disability-epilepsy syndrome	c3463992	28,549	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3175	2021-01-23T19:11:02	{"mesh": ["C567924"], "omim": ["308350"], "icd-10": ["G25.3"]}
X-linked adrenal hypoplasia congenita is an inherited disorder that mainly affects males. It involves many hormone-producing (endocrine) tissues in the body, particularly a pair of small glands on top of each kidney called the adrenal glands. These glands produce a variety of hormones that regulate many essential functions in the body. Congenital adrenal hypoplasia is characterized by adrenal insufficiency, which may be life threatening, and hypogonadotropic hypogonadism. Congenital adrenal hypoplasia is caused by mutations in the NR0B1 gene. It 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	X-linked adrenal hypoplasia congenita	c0220766	28,550	gard	https://rarediseases.info.nih.gov/diseases/555/x-linked-adrenal-hypoplasia-congenita	2021-01-18T17:57:04	{"omim": ["300200"], "umls": ["C0220766"], "orphanet": ["95702"], "synonyms": ["X-linked congenital adrenal hypoplasia", "X-linked AHC", "Adrenal hypoplasia congenita", "Congenital adrenal hypoplasia"]}
Pol III-related leukodystrophy is a disorder that affects the nervous system and other parts of the body. Leukodystrophies are conditions that involve abnormalities of the nervous system's white matter, which consists of nerve cells (neurons) covered by a fatty substance called myelin. Myelin insulates nerve fibers and promotes the rapid transmission of nerve impulses. Pol III-related leukodystrophy is a hypomyelinating disease, which means that the nervous system of affected individuals has a reduced ability to form myelin. Hypomyelination underlies most of the neurological problems associated with Pol III-related leukodystrophy. A small number of people with this disorder also have a loss of nerve cells in a part of the brain involved in coordinating movements (cerebellar atrophy) and underdevelopment (hypoplasia) of tissue that connects the left and right halves of the brain (the corpus callosum). These brain abnormalities likely contribute to the neurological problems in affected individuals. People with Pol III-related leukodystrophy usually have intellectual disability ranging from mild to severe, which gradually worsens over time. Some affected individuals have normal intelligence in early childhood but develop mild intellectual disability during the course of the disease. Difficulty coordinating movements (ataxia), which begins in childhood and slowly worsens over time, is a characteristic feature of Pol III-related leukodystrophy. Affected children typically have delayed development of motor skills such as walking. Their gait is unstable, and they usually walk with their feet wide apart for balance. Affected individuals may eventually need to use a walker or wheelchair. Involuntary rhythmic shaking (tremor) of the arms and hands may occur in this disorder. In some cases the tremor occurs mainly during movement (intention tremor); other affected individuals experience the tremor both during movement and at rest. Development of the teeth (dentition) is often abnormal in Pol III-related leukodystrophy, resulting in the absence of some teeth (known as hypodontia or oligodontia). Some affected infants are born with a few teeth (natal teeth), which fall out during the first weeks of life. The primary (deciduous) teeth appear later than usual, beginning at about age 2. In Pol III-related leukodystrophy, the teeth may not appear in the usual sequence, in which front teeth (incisors) appear before back teeth (molars). Instead, molars often appear first, with incisors appearing later or not at all. Permanent teeth are also delayed, and may not appear until adolescence. The teeth may also be unusually shaped. Some individuals with Pol III-related leukodystrophy have excessive salivation and difficulty chewing or swallowing (dysphagia), which can lead to choking. They may also have speech impairment (dysarthria). People with Pol III-related leukodystrophy often have abnormalities in eye movement, such as progressive vertical gaze palsy, which is restricted up-and-down eye movement that worsens over time. Nearsightedness is common in affected individuals, and clouding of the lens of the eyes (cataracts) has also been reported. Deterioration (atrophy) of the nerves that carry information from the eyes to the brain (the optic nerves) and seizures may also occur in this disorder. Hypogonadotropic hypogonadism, which is a condition caused by reduced production of hormones that direct sexual development, may occur in Pol III-related leukodystrophy. Affected individuals have delayed development of the typical signs of puberty, such as the growth of body hair. People with Pol III-related leukodystrophy may have different combinations of its signs and symptoms. These varied combinations of clinical features were originally described as separate disorders. Affected individuals may be diagnosed with ataxia, delayed dentition, and hypomyelination (ADDH); hypomyelination, hypodontia, hypogonadotropic hypogonadism (4H syndrome); tremor-ataxia with central hypomyelination (TACH); leukodystrophy with oligodontia (LO); or hypomyelination with cerebellar atrophy and hypoplasia of the corpus callosum (HCAHC). Because these disorders were later found to have the same genetic cause, researchers now group them as variations of the single condition Pol III-related leukodystrophy. ## Frequency Pol III-related leukodystrophy is a rare disorder; its prevalence is unknown. More than 100 affected individuals have been described in the medical literature. ## Causes Pol III-related leukodystrophy is caused by mutations in the POLR3A or POLR3B gene. These genes provide instructions for making the two largest parts (subunits) of an enzyme called RNA polymerase III. This enzyme is involved in the production (synthesis) of ribonucleic acid (RNA), a chemical cousin of DNA. The RNA polymerase III enzyme attaches (binds) to DNA and synthesizes RNA in accordance with the instructions carried by the DNA, a process called transcription. RNA polymerase III helps synthesize several forms of RNA, including ribosomal RNA (rRNA) and transfer RNA (tRNA). Molecules of rRNA and tRNA assemble protein building blocks (amino acids) into working proteins; this process is essential for the normal functioning and survival of cells. Researchers suggest that mutations in the POLR3A or POLR3B gene may impair the ability of subunits of the RNA polymerase III enzyme to assemble properly or result in an RNA polymerase III with impaired ability to bind to DNA. Reduced function of the RNA polymerase III molecule likely affects development and function of many parts of the body, including the nervous system and the teeth, but the relationship between POLR3A and POLR3B gene mutations and the specific signs and symptoms of Pol III-related leukodystrophy is unknown. ### Learn more about the genes associated with Pol III-related leukodystrophy * POLR3A * POLR3B ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Pol III-related leukodystrophy	c2676243	28,551	medlineplus	https://medlineplus.gov/genetics/condition/pol-iii-related-leukodystrophy/	2021-01-27T08:25:25	{"mesh": ["C567313"], "omim": ["607694", "614381"], "synonyms": []}
A rare, genetic, renal tubular disease characterised by nephrogenic diabetes insipidus, intracerebral calcifications, intellectual disability, short stature and facial dysmorphism. There have been no further descriptions in the literature since 1990. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Nephrogenic diabetes insipidus-intracranial calcification-facial dysmorphism syndrome	c2931070	28,552	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3145	2021-01-23T18:18:18	{"gard": ["259"], "mesh": ["C535949"], "omim": ["221995"], "umls": ["C2931070"], "icd-10": ["N21.5"]}
Glioependymal/ependymal cyst is a rare central nervous system malformation defined as a subarachnoid, supratentorial, interventricular or intraspinal, sometimes intracerebral or intramedullar cyst with an internal ependymal lining, possibly surrounded by glial tissue. It may be an incidental finding or may present at different ages with clinical features depending on its size and location. It may distort adjacent brain structures and cause macrocephaly, ventriculomegaly, hydrocephalus, focal neurological signs and other signs and symptoms. In some cases, it is associated with other cerebral malformations (e.g. corpus callosum agenesis, polymicrogyria, heterotopias). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Glioependymal/ependymal cyst	None	28,553	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=269197	2021-01-23T18:35:58	{}
Charcot-Marie-Tooth type 4 (CMT4) is a congenital neurologic hereditary disease, part of a group of peripheral neuropathies known as Charcot-Marie-Tooth disease (CMT). According to the mutated gene CMT4 is classified in CMT4A, CMT4B1, CMT4B2, CMT4B3, CMT4C, CMT4D, CMT4E, CMT4F, CMT4G, CMT4H and CMT4J. Each of these subtypes is very rare and may affect only a particular ethnic group. CMT4 causes weakness, usually mostly distal (situated away from the center of the body) but sometimes involving proximal (near the center of the body) muscles. The most common symptoms are walking difficulties with steppage gait or an abnormally high arched foot (pes cavus) pes cavus. Hammer toes and other skeletal deformities, such as an abnormal lateral curvature of the spine (scoliosis), are often observed. Some affected people have changes in sensations (such as the sense of touch or ability to perceive temperature changes). When CMT4 begins in infancy, it is characterized by low muscle tone. CMT4 patients may also develop other symptoms such as cataracts or deafness. Generally, cases of CMT4 present earlier and with more severe symptoms compared to CMT1 or CMT2. Subtypes may have different clinical features among them. Several genes have been identified as causing CMT4, including GDAP1 (CMT4A), MTMR13 (CMT4B1), MTMR2 (CMT4B2), SBF1 (CMT4B3), SH3TC2 (CMT4C), NDG1(CMT4D), EGR2 (CMT4E), PRX (CMT4F), FDG4 (CMT4H), and FIG4 (CMT4J). CMT4 inheritance is autosomal recessive. Treatment is symptomatic and includes physical therapy, corrective surgery (when needed) and pain medication. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Charcot-Marie-Tooth disease type 4	c4082197	28,554	gard	https://rarediseases.info.nih.gov/diseases/12440/charcot-marie-tooth-disease-type-4	2021-01-18T18:01:30	{"orphanet": ["64749"], "synonyms": ["CMT4", "Autosomal recessive demyelinating Charcot-Marie-Tooth", "AR-CMT1"]}
## Description The paraoxonase (PON) gene family includes 3 genes, PON1, PON2 (602447), and PON3 (602720), aligned next to each other on chromosome 7. PON1 (EC 3.1.1.2) hydrolyzes the toxic oxon metabolites of several organophosphorous insecticides, including parathion, diazinon, and chlorpyrifos, as well as nerve agents, such as sarin and soman. PON1 also hydrolyzes aromatic esters, preferably those of acetic acid. In addition, PON1 hydrolyzes a variety of aromatic and aliphatic lactones, and it also catalyzes the reverse reaction, lactonization, of gamma- and delta-hydroxycarboxylic acids. Human PON1 is synthesized in liver and secreted into blood, where it is associated exclusively with high density lipoproteins (HDLs) and may protect against development of atherosclerosis (Draganov et al., 2005). Cloning and Expression Hassett et al. (1991) isolated a full-length PON1 cDNA from a human liver cDNA library using rabbit Pon1 as a hybridization probe. The deduced PON1 protein contains 355 amino acids and is more than 85% similar to the rabbit protein. N-terminal sequences derived from purified rabbit and human PON1 proteins suggested that the PON1 signal sequence is retained, except for the initiator methionine. Characterization of the rabbit and human PON1 cDNAs confirmed that the signal sequences are not processed, except for the N-terminal methionine. Using SDS-PAGE, Draganov et al. (2005) found that PON1 appeared as a doublet of about 39 and 42 kD. However, using nondenaturing PAGE, they observed human serum PON1 and recombinant PON1 at apparent molecular masses of 91.9 and 95.6 kD, respectively, suggesting that PON1 forms dimers. Glycosidase treatment of human serum PON1 suggested that the secreted form of PON1 contains complex carbohydrates. Lu et al. (2006) stated that human PON1, PON2, and PON3 have 3 conserved cysteines. Cys41 and cys351 are predicted to form an intramolecular disulfide bond, and cys283 is predicted to be involved in antioxidant activity. Gene Structure Clendenning et al. (1996) characterized a 28-kb contig encompassing 300 bp of 5-prime sequence, the entire coding region, and 2 kb of 3-prime flanking sequence of the PON1 gene. The structural portion of the paraoxonase protein is encoded by 9 exons that form the primary transcript through the use of typical splice donor and acceptor sites. Sorenson et al. (1995) showed that the Pon1 gene in mice contains 9 exons spanning approximately 25 to 26 kb. Mapping Eiberg and Mohr (1979) presented linkage data. No linkage with any of 19 markers was found by Mueller et al. (1983). Eiberg et al. (1985) showed that cystic fibrosis (219700) and PON are linked on chromosome 7 (maximum lod 3.70 at theta = 0.07 in males and 0.00 in females)--the first step in the cloning of the CF gene in 1989. Tsui et al. (1985) confirmed the PON-CF linkage by finding linkage of PON to a DNA marker that is also linked to CF. Schmiegelow et al. (1986) found the PON and CF loci linked with lod score of 3.46 at recombination fraction 0.07 in males and 0.13 in females. By in situ hybridization, Humbert et al. (1993) demonstrated that the PON gene maps to chromosome 7q21-q22. Mochizuki et al. (1998) pointed out that the PON1, PON2, and PON3 genes are physically linked on chromosome 7q21.3. Sorenson et al. (1995) mapped the mouse Pon1 gene to the proximal end of chromosome 6 by interspecific backcross analysis. Li et al. (1997) likewise mapped the gene to mouse chromosome 6. Gene Function Simpson (1971) found a unimodal distribution of serum arylesterase activity in 176 individuals. There was no difference in enzyme activity between sexes, but the level of activity gradually increased with age. From a study of twins, heritability of arylesterase activity was estimated to be 74%. Data from parent pairs suggested that, in addition to genetic and age factors, unknown nongenetic factors substantially affected enzyme activity. Eckerson et al. (1983) concluded that arylesterase activity, measured with phenylacetate as substrate, and paraoxonase activity are determined by the same gene. They used the designation esterase A for the paraoxonase/arylesterase enzyme (see HISTORY for information on the identification and classification of esterases). Furlong et al. (1991) also demonstrated that both arylesterase and paraoxonase activities are expressed by a single enzyme. Furlong et al. (1988) studied hydrolysis of an insecticide metabolite, chlorpyrifos oxon, by PON1. The physiologic role of paraoxonase in detoxication and in intermediary metabolism is uncertain (La Du, 1988). However, animal studies, including examination of quantitative adequacy of PON and protection against paraoxon toxicity, correlation of LD50 values with PON levels, and demonstration that intravenously injected PON provides protection against paraoxon toxicity, indicate that serum PON is protective against organophosphate poisoning (reviewed by Humbert et al., 1993). In a series of animal experiments, Navab et al. (1997) demonstrated that the ratio of Apoj (185430) to Pon was increased in fatty streak-susceptible mice fed an atherogenic diet, in Apoe knockout mice on a chow diet, in LDL receptor (LDLR; 606945) knockout mice on a cholesterol-enriched diet, and in fatty streak-susceptible mice injected with mildly oxidized LDL fed a chow diet. Human studies showed that the APOJ/PON ratio was significantly higher than that of controls in 14 normolipidemic patients with coronary artery disease in whom the cholesterol/HDL ratio did not differ significantly from that of controls. Draganov et al. (2005) found that glycosylation of recombinant PON1 with high-mannose-type sugars did not alter its enzymatic activity, but it may have affected protein stability. They found that PON1, PON2, and PON3, whether expressed in insect or HEK293 cells, metabolized oxidized forms of arachidonic acid and docosahexaenoic acid. Otherwise, the PONs showed distinctive substrate specificities. PON1, but not other PONs, specifically hydrolyzed organophosphates. About 60% of total arylesterase and lactonase activity of PON1-transfected HEK293 cells was secreted into the culture medium. Draganov et al. (2005) found that recombinant PONs did not protect human LDL against Cu(2+)-induced oxidation in vitro, and no antioxidant activity copurified with any of the PONs. They stated that they had previously copurified antioxidant activity with human serum PON1, but that it was attributable to a low molecular mass contaminant and to the detergent in the preparation. Molecular Genetics ### Variation in PON1 Enzyme Activity Geldmacher-von Mallinck et al. (1973) first found polymorphism of paraoxonase activity. Playfer et al. (1976) found bimodality for plasma paraoxonase activity in British and Indian persons, defining low and high activity phenotypes. Study of 40 British families confirmed this genetic polymorphism. Two phenotypes controlled by 2 alleles at 1 autosomal locus were defined. The frequency of the low activity phenotype was lower in the Indian population than in the British population. Malay, Chinese, and African populations failed to show clear bimodality. Possibly multiple alleles are present in these populations and result in a continuous distribution. Mueller et al. (1983) described a test based on the differential inhibition of EDTA of plasma paraoxonase from persons with the high activity allele. With this test, trimodality of activity levels was suggested by population studies. The gene frequency of the low activity allele in 531 Seattle blood donors of European origin was 0.72. Family studies were consistent with codominant autosomal inheritance of 2 alleles encoding products with low and high activity levels. Eckerson et al. (1983) could clearly distinguish heterozygotes from both homozygous phenotypes on the basis of the ratio of paraoxonase to arylesterase activities. Ortigoza-Ferado et al. (1984) concluded that albumin has paraoxonase activity and proposed that an optimal assay of polymorphic paraoxonase activity should be based on activity of the nonalbumin fraction. Nielsen et al. (1986) reexamined extensive family data and reaffirmed that segregation into high and low paraoxonase activity is largely or exclusively due to a 1-locus system. Humbert et al. (1993) found that arginine at position 192 of PON1 specifies high-activity plasma paraoxonase, whereas glutamine at this position specifies a low-activity variant (Q192R; 168820.0001). This polymorphism is also referred to as gln191 to arg. Adkins et al. (1993) demonstrated that glutamine or arginine at amino acid 191 determines the A and B allozymes, respectively, of PON1. In a study of 376 white individuals, Brophy et al. (2001) determined the genotypes of 3 regulatory region polymorphisms and examined their effect on plasma PON1 levels as indicated by rates of phenylacetate hydrolysis. The -108C-T polymorphism (168820.0003) had a significant effect on PON1 activity level, whereas a polymorphism at position -162 had a lesser effect. A polymorphism at position -909, which is in linkage disequilibrium with the other sites, appeared to have little or no independent effect on PON1 activity level in vivo. Brophy et al. (2001) presented evidence that the effect of the L55M (168820.0002) polymorphism on lowered paraoxonase activity is not due primarily to the amino acid change itself but to linkage disequilibrium with the -108C-T regulatory region polymorphism. The L55M polymorphism marginally appeared to account for 15.3% of the variance in PON1 activity, but this dropped to 5% after adjustments for the effects of the -108C-T and Q192R polymorphisms were made. The -108C-T polymorphism accounted for 22.8% of the observed variability in PON1 expression levels, which was much greater than that attributable to other PON1 polymorphisms. Using a validated microsomal expression system of metabolizing enzymes, Bouman et al. (2011) identified PON1 as the crucial enzyme for the bioactivation of the antiplatelet drug clopidogrel, with the common Q192R polymorphism determining the rate of active metabolite formation. Analysis of patients with coronary artery disease who underwent stent implantation and received clopidogrel therapy revealed that Q192 homozygotes were more likely to undergo stent thrombosis than patients with the RR192 or QR192 genotypes (odds ratio, 3.6; p = 0.0003). ### Susceptibility to Organophosphate Poisoning PON1 hydrolyzes diazinonoxon, the active metabolite of diazinon, which is an organophosphate used in sheep dip. Cherry et al. (2002) studied PON1 polymorphisms in 175 farmers with ill health that they attributed to sheep dip and 234 other farmers nominated by the ill farmers and thought to be in good health despite having also dipped sheep. They calculated odds ratios for the Q192R (168820.0001) and L55M (168820.0002) polymorphisms, and for PON1 activity with diazinonoxon as substrate. Cases were more likely than referents to have at least 1 R allele at position 192 (odds ratio 1.93), both alleles of type LL (odds ratio 1.70) at position 55, and to have diazoxonase activity below normal median (odds ratio 1.77). The results supported the hypothesis that organophosphates contribute to the reported ill health of people who dip sheep. ### Susceptibility to Coronary Artery Disease Serrato and Marian (1995), who referred to the gln192-to-arg (Q192R; 168820.0001) polymorphism as the A/G polymorphism or the A/B polymorphism, demonstrated a relationship to coronary artery disease. The A and G alleles code for glutamine (A genotype) and arginine (B genotype), respectively. Individuals with the A genotype have a lower enzymatic activity than those with the B genotype. Serrato and Marian (1995) determined the genotypes in 223 patients with angiographically documented coronary artery disease and in 247 individuals in the general population. The distribution of genotypes was in Hardy-Weinberg equilibrium in both groups. Genotypes A and B were present in 49% and 11% of control individuals and in 30% and 18% of patients with coronary artery disease, respectively (p = 0.0003). The frequency of the A allele was 0.69 in controls and 0.56 in patients (p = 0.0001). There was no difference in the distribution of PON genotypes in the subgroups of patients with restenosis, myocardial infarction, or any of the conventional risk factors for coronary artery disease as compared with corresponding subgroups. The L55M and Q192R polymorphisms in the PON1 gene and the ser311-to-cys (S311C; 602447.0001) polymorphism in the PON2 gene are associated with the risk of coronary artery disease in several European or European-derived populations. Chen et al. (2003) examined the association between these 3 markers and the severity of coronary artery disease as determined by the number of diseased coronary artery vessels in 711 women. No significant association was found between the PON polymorphisms and stenosis severity in either white or black women. However, among white women, when data were stratified by the number of diseased vessels, the frequency of the PON codon 192 arg/arg genotype was significantly higher in the group with 3-vessel disease than in the other groups (those with 1-vessel and 2-vessel disease) combined. Similarly, the frequency of the PON2 codon 311 cys/cys genotype was significantly higher in the group with 3-vessel disease than in the other groups combined. The adjusted odds ratio for the development of 3-vessel disease was 2.80 for PON1 codon 192 arg/arg and 3.68 for PON2 codon 311 cys/cys. The data indicated that the severity of coronary artery disease, in terms of the number of diseased vessels, may be affected by common genetic variation in the PON gene cluster on chromosome 7. Garin et al. (1997) identified homozygosity for the leu54 allele of PON1 (168820.0002), which is associated with high paraoxonase activity, as an independent risk factor for cardiovascular disease. A linkage disequilibrium was apparent between the polymorphisms giving rise to leu54 and arg191. Garin et al. (1997) stated that their study underlined the fact that susceptibility to cardiovascular disease correlated with high-activity paraoxonase alleles. Linkage disequilibrium could explain the association between both the leu54 and the arg191 polymorphisms and cardiovascular disease. ### Susceptibility to Coronary Artery Spasm Ito et al. (2002) found that the incidence of the PON1 192R allele was significantly higher in a cohort of 214 Japanese patients with coronary spasm than in 212 control subjects. They speculated that the high frequency of the PON1 arg192 allele may be related to the higher prevalence of coronary spasm among Japanese than among Caucasians. ### Susceptibility to Microvascular Complications of Diabetes 5 Kao et al. (1998) found an association between the L55M polymorphism in the PON1 gene (168820.0002) and diabetic retinopathy (MVCD5; 603933) in patients with type 1 diabetes (222100). Kao et al. (2002) confirmed the association between L55M and diabetic retinopathy, finding increased susceptibility for retinopathy with the leu/leu genotype (odds ratio 3.34; p less than 0.0001). ### Other Associations Ikeda et al. (2001) found that the distribution of the Q192R and L55M (168820.0002) polymorphisms in the PON1 gene was significantly different between Japanese patients with exudative age-related macular degeneration (ARMD; see 153800) and age- and sex-matched controls. The BB genotype at position 192 and the LL genotype at position 55 occurred at higher frequency in patients with ARMD compared to controls (p = 0.0127 and p = 0.0090, respectively). The mean oxidized LDL level in patients was significantly higher than in controls (p less than 0.01). Ikeda et al. (2001) concluded that the PON1 gene polymorphisms might represent a genetic risk factor for ARMD and that increased plasma oxidized LDL might be involved in the pathogenesis of ARMD. Data on gene frequencies of allelic variants were tabulated by Roychoudhury and Nei (1988). Genotype/Phenotype Correlations Davies et al. (1996) analyzed the paraoxonase catalytic activity against the toxic oxon forms which result from the bioactivation of the organophosphorus insecticides parathion, chlorpyrifos, and diazinon in the P450 system. They also analyzed the hydrolytic activity of PON1 against the nerve agents soman and sarin. Davies et al. (1996) reported a simple enzyme analysis that provided a clear resolution of PON1 genotypes and phenotypes. The plot of diazoxon hydrolysis versus paraoxon hydrolysis clearly resolved all 3 genotypes (Q192Q192, Q191R192, R192R192; see 168820.0001) and at the same time provided important information about the level of enzyme activity in an individual. They observed the reversal of the effect of PON1 polymorphisms for diazoxon hydrolysis relative to paraoxon hydrolysis. RR homozygotes (high paraoxonase activity) had lower diazoxonase activity than the QQ homozygotes (low paraoxonase activity). They reported that the effect was also reversed for the nerve gases soman and sarin (sarin was the nerve gas released in the Tokyo subway in March 1995). The mean value of sarin hydrolysis was only 38 U per liter for the R192 homozygotes compared with 355 U per liter for the Q192 homozygotes. Davies et al. (1996) observed an increased frequency for the R192 allele (0.41) in the Hispanic population compared with a frequency of 0.31 for populations of northern European origin. These frequencies result in approximately 16% of individuals of Hispanic origin being homozygous for the R192 PON1 isoform compared with 9% of individuals of northern European origin. They noted that newborns have very low activities of PON1, leading them to predict that newborns would be significantly more sensitive to organophosphorus compounds than adults. The authors cited studies showing that injected PON1 protects against organophosphorus poisoning in rodents (Li et al., 1995). Phuntuwate et al. (2005) studied the activity of 4 PON1 polymorphisms towards paraoxon, phenylacetate, and diazoxon. They found that the L55M, Q192R, and -909G-C polymorphisms significantly and variably affected serum PON1 activity towards the substrates, whereas the -108C-T polymorphism had no significant effect on serum PON1 activity towards any substrate. Phuntuwate et al. (2005) suggested that the physiologic relevance of the PON1 polymorphisms is that they are associated with significant differences in serum PON1 activity that are substrate dependent. Mackness et al. (1998) examined the effects of the 2 common polymorphisms in PON1 on the ability of HDL to protect LDL from oxidative modification. HDL protected LDL from oxidative modification, whatever the combination of PON1 alloenzymes present in it. However, HDL from QQ/MM homozygotes was most effective in protecting LDL, while HDL from RR/LL homozygotes was least effective. Thus after 6 hours of coincubation of HDL and LDL with Cu(2+), PON1-QQ HDL retained 57 +/- 6.3% of its original ability to protect LDL from oxidative modification, while PON1-QR HDL retained less at 25.1 +/- 4.5% and PON1-RR HDL retained only 0.75 +/- 0.40%. In similar experiments, HDL from LL and LM genotypes retained 21.8 +/- 7.5% and 29.5 +/- 6.6%, respectively, of their protective ability, whereas PON1-MM HDL maintained 49.5 +/- 5.3%. PON1 polymorphisms may affect the ability of HDL to impede the development of atherosclerosis and to prevent inflammation. Evolution Meyer et al. (2018) used phylogenetic methods to identify convergent functional losses across independent marine mammal lineages. They determined that PON1 has accrued lesions in all marine lineages while remaining intact in all terrestrial mammals. These lesions coincide with PON1 enzymatic activity loss in marine species' blood plasma. This convergent loss is likely explained by parallel shifts in marine ancestors' lipid metabolism and/or bloodstream oxidative environment affecting PON1's role in fatty acid oxidation. PON1 loss also eliminates marine mammals' main defense against neurotoxicity from specific man-made organophosphorus compounds, implying potential risks in modern environments. Animal Model To study the role of PON1 in vivo, Shih et al. (1998) created Pon1-knockout mice by gene targeting. Compared with their wildtype littermates, Pon1-deficient mice were extremely sensitive to the toxic effects of chlorpyrifos oxon, the activated form of chlorpyrifos, and were more sensitive to chlorpyrifos itself. HDLs isolated from Pon1-deficient mice were unable to prevent LDL oxidation in a cocultured cell model of the artery wall, and both HDLs and LDLs isolated from Pon1-knockout mice were more susceptible to oxidation by cocultured cells than were lipoproteins from wildtype littermates. When fed on a high-fat, high-cholesterol diet, Pon1-null mice were more susceptible to atherosclerosis than were their wildtype littermates. Watson et al. (2001) identified a serum paraoxonase polymorphism in rabbit with functional characteristics similar to those of human Q192R. They suggested that the rabbit may serve as a model in examining the effect of human PON1 polymorphisms in disease development. History ### Identification and Classification of Esterases Using azo dye coupling techniques and electrophoresis, Tashian (1965) defined several different esterases in human red cells. Three main groups, differing as to electrophoretic properties, substrate specificities and inhibition characteristics, were A, B, and C esterases. Variants of esterase A were reported by Tashian and Shaw (1962) and Tashian (1965). Using starch-gel electrophoresis, Coates et al. (1975) identified multiple esterase isozymes in every human tissue, and they characterized the isozymes in terms of electrophoretic mobility, tissue distribution, developmental changes in utero, substrate specificity, inhibition properties, and molecular weight. On these criteria, 13 sets of esterase isozymes were identified, in addition to the esterase isozymes due to cholinesterase and carbonic anhydrase. The data suggested that the 13 sets of isozymes are determined by at least 9 different genes. The acetylesterases, which prefer acetate esters as substrates, were divided into 9 sets of isozymes, designated ESA1 to ESA7, ESC (133270), and ESD (133280). Coates et al. (1975) divided the butyrylesterases, which prefer butyrate esters as substrates, into 4 sets of isozymes, designated ESB1 to ESB4. Misc \- Organophosphate poisoning sensitvity Lab \- Low paroxonase (arylesterase hydrolyzing paroxon to produce p-nitrophenol) Inheritance \- Autosomal dominant (7q21-q22) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	PARAOXONASE 1	c1840169	28,555	omim	https://www.omim.org/entry/168820	2019-09-22T16:36:33	{"omim": ["168820"], "synonyms": ["Alternative titles", "PON", "PARAOXONASE, PLASMA", "ARYLESTERASE", "ESTERASE A"]}
A number sign (#) is used with this entry because of evidence that orthostatic intolerance is caused by heterozygous mutation in the gene encoding the norepinephrine transporter (SLC6A2; 163970) on chromosome 16q12. One such family has been reported. Clinical Features Orthostatic intolerance is a syndrome characterized by adrenergic symptoms that occur when an upright posture is assumed: the heart rate increases by at least 30 beats per minute, without orthostatic hypotension (Jacob et al., 1997). Most patients with orthostatic intolerance are women between the ages of 20 and 50 years (Low et al., 1995). This syndrome, first described by Da Costa (1871), has been called soldiers heart (Fraser and Wilson, 1918), neurocirculatory asthenia (Wooley, 1976), and mitral valve prolapse syndrome (Boudoulas et al., 1980). It is similar in many respects to chronic fatigue syndrome (Schondorf and Freeman, 1999). Molecular Genetics In a family with orthostatic intolerance, Shannon et al. (2000) identified heterozygosity for a mutation in the SLC6A2 gene (163970.0001). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	ORTHOSTATIC INTOLERANCE	c1535893	28,556	omim	https://www.omim.org/entry/604715	2019-09-22T16:11:49	{"doid": ["0111154"], "mesh": ["D054971"], "omim": ["604715"], "orphanet": ["443236"], "synonyms": ["NEUROCIRCULATORY ASTHENIA", "MITRAL VALVE PROLAPSE SYNDROME", "Alternative titles", "SOLDIERS HEART", "IRRITABLE HEART", "Orthostatic intolerance due to NET deficiency", "POTS due to NET deficiency", "Familial orthostatic tachycardia due to norepinephrine transporter deficiency"]}
From Berne, Tonz et al. (1961) reported 2 brothers, aged 7 and 14 years, with hemolytic disease already manifest in the first weeks of life. Chronic jaundice, severe anemia and splenomegaly were features. Splenectomy was of some benefit. Several enzymes of the erythrocyte were normal, but pyruvate kinase activity was not measured. The urine consistently showed an increased amount of porphobilinogen and delta-aminolevulinic acid. A defect in porphyrin metabolism (i.e., heme synthesis) was suggested. Since the ancestors of the Amish cases of pyruvate kinase deficiency (266200) first reported by Bowman and Procopio originated in the canton Berne, studies of pyruvate kinase (609712) are particularly pertinent. Skin \- Jaundice Inheritance \- Autosomal recessive Abdomen \- Splenomegaly Lab \- Elevated urinary porphobilinogen \- Elevated urinary delta-aminolevulinic acid Heme \- Nonspherocytic hemolytic anemia ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	ANEMIA, NONSPHEROCYTIC HEMOLYTIC, POSSIBLY DUE TO DEFECT IN PORPHYRIN METABOLISM	c1859785	28,557	omim	https://www.omim.org/entry/206400	2019-09-22T16:31:08	{"mesh": ["C565952"], "omim": ["206400"]}
A number sign (#) is used with this entry because of evidence that susceptibility to obesity can be influenced by variation in the FTO gene (610966) on chromosome 16q12. For a phenotypic description and a discussion of genetic heterogeneity of body mass index (BMI), see 606641. Mapping Frayling et al. (2007) identified a common variant in the FTO gene (610966) on 16q12.2 as a risk factor for obesity. The authors performed a genomewide association study of type II diabetes by screening 1,924 patients and 2,938 controls from the UK for more than 490,000 autosomal SNPs. SNPs in the FTO region showed strong association (as high as p of 5 x 10(-8) for rs9939609) in this screen and in a replication study with an additional 3,757 type II diabetics and 5,346 controls (p of 9 x 10(-6) for rs9939609). The diabetes risk alleles at FTO were strongly associated with increased BMI, and further analysis showed that the association of the FTO SNPs with type II diabetes was mediated through an increased risk for BMI. Frayling et al. (2007) analyzed an additional 19,424 white European adults from 7 population-based studies and 10,172 white European children from 2 population-based studies and confirmed association of the A allele of rs9939609 with increased BMI. In all adult population-based studies, the risk for higher BMI was additive, such that those homozygous for the A allele had a higher BMI than those heterozygous for the A allele and the low-risk T allele. When all the data were combined, the p value was 3 x 10(-35), or 1.2 x 10(-29) when a Bonferroni correction was performed for the approximately 400,000 SNPs tested. The attributable risk for rs9939609 was approximately 20% for obesity (BMI more than 30 kg/m2) and approximately 13% for being overweight (BMI more than 25 kg/m2). Overall, Frayling et al. (2007) determined that about 16% of white Europeans are homozygous for the A allele of rs9939609 and are 1.67 times as likely to be obese compared with those homozygous for the T allele. Study of at-risk children showed that rs9939609 was associated with increased BMI and obesity by the age of 7 years. Frayling et al. (2007) determined that rs9939609 occurs in intron 1 of the FTO gene and is highly correlated with 45 other SNPs within a 47-kb region encompassing the first 2 introns and exon 2. It was not clear which, if any, of these SNPs represented the functional variant, and sequence analysis of 47 patients with a BMI of more than 40 kg/m2 did not reveal any obvious functional variants in the FTO coding region, minimal splice sites, or 3-prime UTR. Frayling et al. (2007) noted that the FTO gene is closely adjacent to the KIAA1005 gene (RPGRIP1L; 610937), which is transcribed in the opposite orientation and shows a similar expression profile, suggesting that the FTO SNPs may have an effect on KIAA1005 regulation. Dina et al. (2007) identified 2 potentially functional SNPs in intron 1 of the FTO gene that were consistently strongly associated with early-onset and severe obesity in 2,900 affected individuals and 5,100 controls (p = 1.67 x 10 (-26) for the C allele of rs1421085 and p = 1.07 x 10 (-24) for the G allele of rs17817449). The at-risk haplotype yielded a proportion of attributable risk of 22% for common obesity. Dina et al. (2007) concluded that FTO contributes to human obesity, and noted that there were at least 44 not-yet-genotyped SNPs in linkage disequilibrium with these 2 markers. Ohashi et al. (2007) found no association between the SNPs rs9939609, rs1421085, and rs17817449 in the FTO gene and BMI in Oceanic populations (4 Melanesian, 1 Micronesian, and 1 Polynesian). Loos et al. (2008) performed a metaanalysis of data from 4 European population-based studies and 3 disease-case series, involving a total of 16,876 individuals of European descent, and confirmed the previously reported association between the FTO gene and BMI (p = 3.6 x 10(-8) at rs1121980). Wardle et al. (2008) genotyped the intronic FTO SNP rs9939609 in 3,337 United Kingdom children in whom measures of habitual appetitive behavior had been assessed using 2 scales (Satiety Responsiveness and Enjoyment of Food) from the Child Eating Behaviour Questionnaire, a psychometric tool that has been validated against objective measures of food intake. The A allele was associated with increased adiposity in this cohort and in an independent case-control replication study of United Kingdom children of similar age. AA homozygotes had significantly reduced Satiety Responsiveness scores (p = 0.008). Mediation analysis indicated that the association of the AA genotype with increased adiposity was explained in part through effects on Satiety Responsiveness. Cecil et al. (2008) genotyped 2,726 Scottish children for the FTO variant rs9939609 and found that the A allele was associated with increased weight and BMI (p = 0.003 for both). In an intensively phenotyped subsample of 97 children, the A allele was also associated with increased fat mass (p = 0.01) but not with lean mass. Although total and resting energy expenditure was increased in children with the A allele (p = 0.009 and p = 0.03, respectively), it was consistent with their increased body mass. The A allele was associated with increased energy intake (p = 0.006) independently of body weight; however, the weight of the food ingested by the children who had the A allele was similar to that of children who did not. Cecil et al. (2008) concluded that the FTO variant that confers a predisposition to obesity may play a role in the control of food intake and food choice, perhaps involving a hyperphagic phenotype or a preference for energy-dense foods. In a study of 15,931 Swedish adults without diabetes, Jonsson and Franks (2009) found that the minor A allele of rs9939609 was associated with increased BMI (p less than 0.001 for AA vs TT or TA genotypes) and, after adjustment for age, sex, and BMI, also with self-reported increased physical activity levels (p = 0.02). Palmer et al. (2009) stated that they had confirmed the previously reported findings by Cecil et al. (2008) regarding an association between rs9939609 and measured intake and preferential selection of energy-rich foods in a questionnaire-based study of more than 6,000 children. Meyre et al. (2009) analyzed genomewide association data from 1,380 Europeans with early-onset and morbid adult obesity and 1,416 age-matched normal-weight controls and found the strongest association signal in the first intron of the FTO gene for an imputed SNP rs1421085 (p = 3 x 10(-12)). Subsequent analysis confirmed the association in an additional 14,186 European individuals (combined p = 1.2 x 10(-28)). Renstrom et al. (2009) performed association studies between 9 SNPs from 9 target genes and adiposity and type 2 diabetes (125853) in 3,885 nondiabetic and 1,038 diabetic Swedish adults. In models with BMI, adipose mass traits, or obesity as outcomes, rs1121980 in the FTO gene was the most strongly associated SNP (p less than 0.0001, p = 0.0007, p = 0.0016, respectively) in 3,885 nondiabetic individuals. Willer et al. (2009) performed a metaanalysis of 15 genomewide association studies for BMI comprising 32,387 participants and followed up top signals in 14 additional cohorts comprising 59,082 participants. They strongly confirmed association with FTO, represented by rs9939609, as associated with obesity with a per-allele change in BMI of 0.33 and an overall P value of 4.9 x 10(-74). Hardy et al. (2010) genotyped variants in FTO rs9939609 and near MC4R (155541; rs17782313) in 1,240 men and 1,239 women born in 1946 and participating in the MRC National Survey of Health and Development. Birth weight was recorded and height and weight were measured or self-reported repeatedly at 11 time-points between ages 2 and 53 years. Hierarchical mixed models were used to test whether genetic associations with weight or BMI standard deviation scores (SDS) changed with age during childhood and adolescence (2-20 years) or adulthood (20-53 years). The association between FTO rs9939609 and BMI SDS strengthened during childhood and adolescence (rate of change: 0.007 SDS/A-allele/year; p less than 0.001), reached a peak strength at age 20 years (0.13 SDS/A-allele), and then weakened during adulthood (-0.003 SDS/A-allele/year, P = 0.001). MC4R rs17782313 showed stronger associations with weight than BMI; its association with weight strengthened during childhood and adolescence (0.005 SDS/C-allele/year; P = 0.006), peaked at age 20 years (0.13 SDS/C-allele), and weakened during adulthood (-0.002 SDS/C-allele/year, P = 0.05). Hardy et al. (2010) concluded that genetic variants in FTO and MC4R showed similar biphasic changes in their associations with BMI and weight, respectively, strengthening during childhood up to age 20 years and then weakening with increasing adult age. A risk polymorphism for obesity in the FTO gene, the A allele at rs9939609, has population frequencies of 46% in Western and Central Europeans, 51% in Yorubans, and 16% in Chinese individuals (summary by Ho et al., 2010). Interestingly, the effect of FTO on BMI may be mediated through impaired responsiveness to satiety (Wardle et al., 2008). Ho et al. (2010) generated 3D maps of regional brain volume differences in 206 healthy elderly subjects scanned with MRI and genotyped as part of the Alzheimer's Disease Neuroimaging Initiative. Ho et al. (2010) found a pattern of systematic brain volume deficits in carriers of the obesity-associated risk allele versus noncarriers. Relative to structure volumes in the mean template, FTO risk allele carriers versus noncarriers had an average brain volume difference of approximately 8% in the frontal lobes and 12% in the occipital lobes. These regions also showed significant volume deficits in subjects with higher BMI. These brain differences were not attributable to differences in cholesterol levels, hypertension, or the volume of white matter hyperintensities. Ho et al. (2010) concluded that these brain maps revealed that a commonly carried susceptibility allele for obesity is associated with structural brain atrophy, with implications for the health of the elderly. Kilpelainen et al. (2011) noted that while GWAS had identified 32 loci influencing body mass index to that time, this measure does not distinguish lean from fat mass. To identify adiposity loci, Kilpelainen et al. (2011) performed a metaanalysis of associations between 2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (p less than 10(-6)) independent loci in 39,576 individuals. They confirmed the established adiposity locus in FTO (rs8050136, effect allele C, combined p = 2.7 x 10(-26)) and identified 2 new loci associated with body fat percentage, one near IRS1 (147545) and one near SPRY2 (602466). Kilpelainen et al. (2011) noted that the body fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes, and coronary artery disease, and decreased adiponectin levels. Yang et al. (2012) performed a metaanalysis of genomewide association studies of phenotypic variation using approximately 170,000 samples on height and BMI in human populations. They reported evidence that the SNP 7202116 at the FTO gene locus, which is known to be associated with obesity, as measured by mean BMI for each rs7202116 genotype, is also associated with phenotypic variability. The results were not due to scale effects or other artifacts, and the authors found no experimentwise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of approximately 0.5 kg in the standard deviation of weight. Yang et al. (2012) concluded that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The authors also concluded that their BMI results for other SNPs and their height results for all SNPs suggested that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with sample sizes greater than 100,000. Molecular Genetics Using a range of genomic techniques to examine the contribution of a risk haplotype for obesity involving 3 SNPs in introns 1 and 2 of the FTO gene (rs1421085, rs9930506, and rs1558902), Claussnitzer et al. (2015) elucidated a mechanistic basis of the association between the FTO region and obesity. Claussnitzer et al. (2015) obtained the highest phylogenetic module complexity analysis (PMCA) score for rs1421085, which they noted is in perfect linkage disequilibrium with the most significant reported SNP, rs1558902. The authors demonstrated that the rs1421085 T-C alteration disrupts a conserved motif for the regulator gene ARID5B (608538), causing derepression of a potent preadipocyte enhancer and doubling of IRX3 (612985) and IRX5 (606195) expression during early adipocyte differentiation. This results in a cell-autonomous developmental shift from energy-dissipating beige (brite) adipocytes to energy-storing white adipocytes, with a 5-fold reduction in mitochondrial thermogenesis and an increase in lipid storage. Inhibition of Irx3 in adipose tissue in mice reduced body weight and increased energy dissipation without a change in physical activity or appetite. Knockdown of IRX3 or IRX5 in primary adipocytes from homozygous carriers of risk alleles at rs1421085, rs9930506, and rs1558902 restored thermogenesis, increasing it by a factor of 7, whereas overexpression of these genes had the opposite effect in adipocytes from carriers homozygous for the nonrisk variant of these 3 SNPs. Repair of the ARID5B motif in primary adipocytes from a patient with the risk alleles restored IRX3 and IRX5 repression, activated browning expression programs, and restored thermogenesis, increasing it by a factor of 7. Claussnitzer et al. (2015) concluded that the FTO SNP rs1421085 (610966.0003) represents the causal variant that disrupts a pathway for adipocyte thermogenesis involving ARID5B, IRX3, and IRX5, providing a mechanistic basis for the genetic association between FTO and obesity. INHERITANCE \- Autosomal recessive GROWTH Weight \- Susceptibility to obesity MISCELLANEOUS \- Only individuals homozygous for risk or non-risk alleles were studied MOLECULAR BASIS \- Caused by mutation in the fat mass- and obesity-associated gene (FTO, 610966.0003 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	BODY MASS INDEX QUANTITATIVE TRAIT LOCUS 14	c2675914	28,558	omim	https://www.omim.org/entry/612460	2019-09-22T16:01:28	{"omim": ["612460"], "synonyms": ["Alternative titles", "OBESITY, SUSCEPTIBILITY TO"]}
This page does not serve as an official recognition of post-finasteride syndrome by the NIH. Please see our Disclaimer for more details. This page was created to provide a list of resources where you can find more information about reported adverse events of 5-alpha reductase inhibitors, which is sometimes referred to as post-finasteride syndrome. Some patients who have taken finasteride have referred to side effects such as sexual dysfunction and depression (sometimes severe). Limited information is available for patients and healthcare professionals on these side effects and whether or not they are permanent. Studies are underway to better understand the effects of 5-alpha reductase inhibitor drugs. We intend this page to be a place where you can find reliable information, and we will update the page as new information becomes available. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Adverse events of 5-alpha-reductase inhibitors	None	28,559	gard	https://rarediseases.info.nih.gov/diseases/12407/adverse-events-of-5-alpha-reductase-inhibitors	2021-01-18T18:02:14	{"synonyms": ["Post Finasteride syndrome"]}
## Description Primary or spontaneous detachment of the retina occurs due to underlying ocular disease and often involves the vitreous as well as the retina. The precipitating event is formation of a retinal tear or hole, which permits fluid to accumulate under the sensory layers of the retina and creates an intraretinal cleavage that destroys the neurosensory process of visual reception. Vitreoretinal degeneration and tear formation are painless phenomena, and in most cases, significant vitreoretinal pathology is found only after detachment of the retina starts to cause loss of vision or visual field. Without surgical intervention, retinal detachment will almost inevitably lead to total blindness (summary by McNiel and McPherson, 1971). Clinical Features McNiel and McPherson (1971) studied an extensive Texas kindred in which 31 of 181 members over 5 generations had primary retinal detachment, independent of myopia. Onset of disease occurred over a wide age range, with the youngest reported patient presenting at age 7 years. The authors noted that penetrance increased with age, and they suggested that individuals heterozygous for the presumed mutation were likely to become affected if they lived long enough. No features indicative of arthroophthalmopathy (108300) or other dominant syndromes with retinal detachment were reported. Inheritance The transmission pattern of retinal detachment in the family reported by McNiel and McPherson (1971) was consistent with autosomal dominant inheritance. Vogt (1940) found 19 families with retinal detachment in at least 2 generations. Some showed involvement in 3 generations and one in 4 generations. Eyes \- Retinal detachment \- No myopia Inheritance \- Autosomal dominant ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	RETINAL DETACHMENT	c0035305	28,560	omim	https://www.omim.org/entry/180050	2019-09-22T16:35:16	{"mesh": ["D012163"], "omim": ["180050"], "icd-9": ["361.9"], "icd-10": ["H33.2"]}
Multiple congenital anomalies-hypotonia-seizures syndrome type 2 (MCAHS2) is a genetic neurodevelopmental disorder characterized by distinctive facial features, low muscle tone (hypotonia) at birth, myoclonic seizures (which cause jerks or twitches of the upper body, arms, or legs), and various other problems involving the central nervous system, heart, and urinary system. Specific symptoms (especially those not involving the nervous system) and severity vary from person to person, but most children develop severe developmental delay and intellectual disability. This condition is caused by mutations in the PIGA gene on the X chromosome and inheritance is X-linked recessive, so it typically affects boys. However, in some cases, MCAHS2 is not inherited from a parent and is the result of a new mutation occurring for the first time in a person with MCAHS2 (a de novo mutation). Treatment depends on the symptoms present and aims to control symptoms and increase quality of life. The long-term outlook and life expectancy varies depending on severity. Some children with MCAHS2 do not survive beyond infancy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Multiple congenital anomalies-hypotonia-seizures syndrome type 2	c3275508	28,561	gard	https://rarediseases.info.nih.gov/diseases/12777/multiple-congenital-anomalies-hypotonia-seizures-syndrome-type-2	2021-01-18T17:58:55	{"omim": ["300868"], "orphanet": ["300496"], "synonyms": ["Early infantile epileptic encephalopathy 20", "MCAHS type 2", "MCAHS2"]}
A number sign (#) is used with this entry because familial erythrocytosis-1 (ECYT1) is caused by heterozygous mutation in the gene encoding the erythropoietin receptor (EPOR; 133171) on chromosome 19p13. Description Familial erythrocytosis-1 is an autosomal dominant disorder characterized by increased serum red blood cell mass and hemoglobin concentration, hypersensitivity of erythroid progenitors to EPO (133170), and low serum levels of EPO. There is no increase in platelets or leukocytes and the disorder does not progress to leukemia (Kralovics et al., 1998). ### Genetic Heterogeneity of Familial Erythrocytosis See also ECYT2 (263400), caused by mutation in the VHL gene (608537) on chromosome 3p25; ECYT3 (609820), caused by mutation in the EGLN1 gene (606425) on chromosome 1q42; ECYT4 (611783), caused by mutation in the EPAS1 gene (603349) on chromosome 2p21; ECYT5 (617907), caused by mutation in the EPO gene (133170) on chromosome 7q22; ECYT6 (617980), caused by mutation in the HBB gene (141900) on chromosome 11q15; ECYT7 (617981), caused by mutation in the HBA genes (141800; 141850) on chromosome 16p13; and ECYT8 (222800), caused by mutation in the BPGM gene (613896) on chromosome 7q33. Stamatoyannopoulos (1972) reviewed causes of familial erythrocytosis and noted that the disorder may result from defects in the regulation of 2,3-diphosphoglycerate (see 613896 and 222800). Erythrocytosis may also be caused by somatic mutation in the JAK2 (147796) or the SH2B3 (605093) gene on chromosome 9p24 and 12q24, respectively. For a review of the genetics of congenital erythrocytosis, see Bento et al. (2014). Nomenclature The term 'polycythemia' (Greek: 'many cells in the blood') is used interchangeably with 'erythrocytosis,' although the latter term more specifically refers to an increase in the number of circulating differentiated red blood cells (Prchal, 2005; Cario, 2005). 'Erythrocytosis' is the preferred term used here in order to distinguish inherited disorders characterized by increased circulating red blood cells from 'polycythemia vera' (PV; 263300), which is a myeloproliferative disorder associated with somatic mutations in the JAK2 gene (147796). Familial erythrocytosis is also distinct from erythroleukemia (133180), which is considered to be a subtype of acute myelogenous leukemia (AML; 601626) characterized by immature erythroid cells in the bone marrow and peripheral blood. Erythrocytosis can be classified as primary or secondary. Primary erythrocytosis is due to an intrinsic inherited or somatic defect in erythroid progenitor cells resulting in an enhanced response to circulating cytokines. In primary erythrocytosis, the red cell compartment expands independently of extrinsic influences. Familial erythrocytosis-1 is a primary erythrocytosis due to a defect in the EPOR gene that results in enhanced response of erythroid progenitors to physiologic or low levels of erythropoietin. Polycythemia vera is also considered to be a primary erythrocytosis because it is due to a defect in the JAK2 gene within erythroid progenitor cells resulting in constitutive intracellular signaling and clonal proliferation. In contrast, secondary erythrocytosis is driven by hormonal factors extrinsic to the erythroid compartment, such as hypoxia due to lung disease or increased EPO from an EPO-secreting tumor (Prchal, 2005; Cario, 2005; Gregg and Prchal, 2005). Clinical Features Engelking (1920) and Wieland (1932) separately reported a family in which 11 members of 3 generations had erythrocytosis. In some, the abnormality was noted in childhood. A patient reported by Auerback et al. (1958) was again reported by Cassileth and Hyman (1966) with family study. Prchal et al. (1985) reported a family with autosomal dominant inheritance of erythrocytosis. Affected members had increased serum red blood cell mass, increased hemoglobin, and decreased EPO levels. Arterial oxygen levels and blood oxygen affinity were normal. In vitro erythroid colony forming units showed significantly increased stimulation by low levels of EPO. Queisser et al. (1988) described erythrocytosis in 7 members of a family in 4 generations with male-to-male transmission. The propositus was first diagnosed at age 26 years. He had headaches and marked plethora. Erythropoietin levels were not elevated. The disorder was characterized in middle age in other members of the family by hypertension, cardiovascular and thromboembolic phenomena, and abnormal bleeding. The proband was treated successfully with repeated venous phlebotomies. Juvonen et al. (1991) reported a large Finnish family with autosomal dominant erythrocytosis. In vitro studies showed hypersensitivity of erythroid progenitors to EPO. The erythrocytosis had not had any obvious effect on the health or life span of the affected individuals. In fact, many reached an advanced age and 1 won several Olympic gold medals and world championships in endurance sports. Mapping In the large Finnish kindred with familial erythrocytosis reported by Juvonen et al. (1991), de la Chapelle et al. (1993) demonstrated linkage to a highly informative, simple sequence repeat (SSR) polymorphism in the 5-prime region of the EPOR gene (lod score of 6.37). Molecular Genetics In all 29 affected members of a large Finnish family with autosomal dominant erythrocytosis reported by Juvonen et al. (1991), de la Chapelle et al. (1993) identified a heterozygous mutation in the EPOR gene (133171.0001). In 2 unrelated families with autosomal dominant erythrocytosis, Kralovics et al. (1997) identified 2 different heterozygous mutations in the EPOR gene (133171.0004; 133171.0005). The authors noted that most of the described EPOR mutations (6 of 8) associated with polycythemia resulted in an absence of the C-terminal negative regulatory domain of the receptor. In 3 affected members of a family with familial erythrocytosis originally reported by Prchal et al. (1985), Kralovics et al. (1998) identified a heterozygous mutation in the EPOR gene (133171.0006). History Dainiak et al. (1979), Yonemitsu et al. (1973), and Distelhorst et al. (1981) attributed familial erythrocytosis to increased autonomous erythropoietin production. Emanuel et al. (1992) reported studies of 3 extensively affected families with familial and congenital erythrocytosis. Although 13 affected individuals were identified in 4 generations in 1 family, there was no instance of male-to-male transmission; in the second family, however, there were 2 such instances. Another patient was an isolated case. In all 3 families, secondary causes of erythrocytosis were ruled out. Erythropoietin levels were normal or low, even after phlebotomy. No evidence of rearrangement or amplification of the EPOR gene could be demonstrated. Functional studies examining the number and binding affinity of the EPO receptor on erythroid progenitors from 3 of their patients demonstrated no abnormalities. Emanuel et al. (1992) suggested that the erythrocytosis in these families may not involve the EPOR itself, but may have resulted from alterations in postreceptor responses. INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Myocardial infarction Vascular \- Coronary artery disease \- Hypertension \- Peripheral thrombosis RESPIRATORY \- Exertional dyspnea ABDOMEN Spleen \- Splenomegaly SKIN, NAILS, & HAIR Skin \- Plethora NEUROLOGIC Central Nervous System \- Headaches \- Dizziness \- Intracerebral hemorrhage HEMATOLOGY \- Erythrocytosis \- Increased red blood cell mass \- Increased hematocrit \- Increased hemoglobin \- Normal oxygen affinity of hemoglobin \- Hypersensitivity of erythroid colony-forming units to erythropoietin (EPO, 133170 ) LABORATORY ABNORMALITIES \- Low or normal serum erythropoietin MISCELLANEOUS \- Fatigue \- Variable phenotype, some patients have very mild symptoms \- See also ECYT2 ( 263400 ) and ECYT3 ( 609820 ) MOLECULAR BASIS \- Caused by mutation in the erythropoeitin receptor gene (EPOR, 133171.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	ERYTHROCYTOSIS, FAMILIAL, 1	c0152264	28,562	omim	https://www.omim.org/entry/133100	2019-09-22T16:41:26	{"doid": ["0060652"], "omim": ["133100"], "orphanet": ["90042"], "synonyms": ["Alternative titles", "POLYCYTHEMIA, PRIMARY FAMILIAL AND CONGENITAL", "ERYTHROCYTOSIS, AUTOSOMAL DOMINANT BENIGN"], "genereviews": ["NBK395975"]}
Autosomal dominant hyper IgE syndrome (AD-HIES), formerly known as Job syndrome, affects several body systems including the immune system. AD-HIES is characterized by abnormally high levels of an immune system protein called immunoglobulin E (IgE) in the blood. Signs and symptoms may include recurrent infections (e.g., pneumonia, skin infections), eczema, and occasionally bone and tooth abnormalities. The eczema and skin infections may cause rashes, blisters, collections of pus (abscesses), open sores, and scaling of the skin. Some cases of AD-HIES are caused by mutations in the STAT3 gene. In other cases, the cause 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 [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Autosomal dominant hyper IgE syndrome	c3887645	28,563	gard	https://rarediseases.info.nih.gov/diseases/6800/autosomal-dominant-hyper-ige-syndrome	2021-01-18T18:01:57	{"mesh": ["D007589"], "omim": ["147060"], "orphanet": ["2314"], "synonyms": ["AD-HIES", "Hyper Ig E syndrome, autosomal dominant", "HIES autosomal dominant", "Hyperimmunoglobulin E recurrent infection syndrome, autosomal dominant", "AD hyperimmunoglobulin E syndrome", "Job syndrome autosomal dominant"]}
Hypotransferrinemia, is an autosomal recessive metabolic disorder in which the body produces not enough transferrin, a plasma protein that transports iron through the blood.[1][2] Once believed to be a synonyme for atransferrinemia (the total absence of transferrin) today’s science is aware of the fact that hypotransferrinemia is a way more common phenotype of mutations in the HFE- und transferrin genes.[3] Hypotransferrinemia is characterized by hemosiderosis mostly in the brain, heart, liver, skin and testicles. The iron damages can lead to brain damage, heart failure and other severe damages and dysfunctions.[4][5] As of 2020 there is still no causal therapy for primary (genetically caused) hypotransferrinemia. ## Contents * 1 Symptoms and signs * 2 Genetics * 3 Diagnosis * 4 Treatment * 5 See also * 6 References ## Symptoms and signs[edit] The presentation of this disorder entails brain damage, neurological conditions, heart dysfunctions, and any kind of symptoms that arise on the grounds of iron oxidation within human cells caused by non-transferrin (protein) bound iron (NTBI).[6][7][8][9][10] ## Genetics[edit] Protein TF (from TF gene) In terms of genetics of hypotransferrinemia researchers have identified mutations in the TF gene as a probable cause of this genetic disorder in affected people as well as mutations in one of the HFE-genes.[1][11] Transferrin is a serum transport protein that transports iron to the reticuloendothelial system for utilization and erythropoiesis.[12][13][14] Due to a lack of sufficient transferrin excess iron deposits itself in the brain, heart, liver, skin, testicles and joints causes structural damages.[15][16] ## Diagnosis[edit] The diagnosis of hypotransferrinemia is done via the following means to ascertain if an individual has the condition:[1] * Blood tests for iron, transferrin, transferrin saturation and ferritin * Physical exam * Genetic test ## Treatment[edit] Other than for hemochromatosis or atransferrinemia there are no treatment options available for people suffering from hypotransferrinemia. Only symptomatic treatments can be tried to improve the consequences caused by the overload with non-transferrin bound iron (NTBI).[17] ## See also[edit] * Transferrin * Ferritin * HFE (gene) * Hemochromatosis * Atransferrinemia * HFE H63D gene mutation ## References[edit] 1. ^ a b c RESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: Congenital atransferrinemia". www.orpha.net. Retrieved 2017-02-20. 2. ^ "OMIM Entry - # 209300 - ATRANSFERRINEMIA". omim.org. Retrieved 19 February 2017. 3. ^ Linda McManus, Richard Mitchell (2014): Pathobiology of Human Disease: A Dynamic Encyclopedia of Disease Mechanisms. San Antonio, Boston, Elsevier Academic Press 4. ^ Marie-Pascale Beaumont-Epinette et al.: Hereditary hypotransferrinemia can lead to elevated transferrin saturation and, when associated to HFE or HAMP mutations, to iron overload. Blood Cells, Molecules, and Diseases. Volume 54, Issue 2, February 2015, Pages 151-154. https://doi.org/10.1016/j.bcmd.2014.11.020 5. ^ Pierre Brissot: Non-transferrin bound iron: A key role in iron overload and iron toxicity. In: Biochimica et Biophysica Acta 1820(3):403-10. August 2011. DOI: 10.1016/j.bbagen.2011.07.014 6. ^ R.C. Hider, Nature of nontransferrin-bound iron, Eur. J. Clin. Invest. 32 (Suppl. 1, 2002) 50–54. 7. ^ Danilo Milardi, Enrico Rizzarelli (2011): Neurodegeneration: Metallostasis and Proteostasis. Chapter 9. Royal Society of Chemistry. 8. ^ Alizadeh BZ, Njajou OT, Millán MR, Hofman A, Breteler MM, van Duijn CM: HFE variants, APOE and Alzheimer’s disease: Findings from the population-based Rotterdam study. In: Neurobiol Aging. 2009 Feb;30(2):330-2. 9. ^ Berlin D, Chong G, Chertkow H, Bergman H, Phillips NA, Schipper HM: Evaluation of HFE (hemochromatosis) mutations as genetic modifiers in sporadic AD and MCI. In: Neurobiol Aging. 2004 Apr;25(4):465-74. 10. ^ P. Brissot, et al., Non-transferrin bound iron: A key role in iron overload and iron toxicity , Biochim. Biophys. Acta (2011), doi:10.1016/j.bbagen.2011.07.014 11. ^ Porto, Graca; de Sousa, Maria (2000). Barton, James C.; Edwards, Corwin Q. (eds.). Variation of hemochromatosis prevalence and genotype in national groups. In: Hemochromatosis: Genetics, pathophysiology, diagnosis and treatment: Cambridge University Press. ISBN 978-0521593809. 12. ^ Bartnikas, Thomas Benedict (1 August 2012). "Known and potential roles of transferrin in iron biology". BioMetals. 25 (4): 677–686. doi:10.1007/s10534-012-9520-3. PMC 3595092. PMID 22294463. 13. ^ Reference, Genetics Home. "TF gene". Genetics Home Reference. Retrieved 2017-02-20. 14. ^ "OMIM Entry - * 190000 - TRANSFERRIN; TF". omim.org. Retrieved 20 February 2017. 15. ^ Nemeth E, Ganz T (2006). "Regulation of iron metabolism by hepcidin". Annual Review of Nutrition. 26: doi:10.1146/annurev.nutr.26.061505.111303 16. ^ K. Jomova, M. Valko, Advances in metal-induced oxidative stress and human disease, Toxicology 283 (2011) 65–87. 17. ^ Chaim Hershko (2012): Iron Chelation Therapy. Springer Science & Business Media. * v * t * e Metal deficiency and toxicity disorders Iron excess: * Iron overload * Hemochromatosis * Hemochromatosis/HFE1 * Juvenile/HFE2 * HFE3 * African iron overload/HFE4 * Aceruloplasminemia * Atransferrinemia * Hemosiderosis deficiency: * Iron deficiency Copper excess: * Copper toxicity * Wilson's disease deficiency: * Copper deficiency * Menkes disease/Occipital horn syndrome Zinc excess: * Zinc toxicity deficiency: * Acrodermatitis enteropathica Other * Inborn errors of metabolism [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Hypotransferrinemia	None	28,564	wikipedia	https://en.wikipedia.org/wiki/Hypotransferrinemia	2021-01-18T18:40:40	{"wikidata": ["Q85767883"]}
A rare dermatosis characterized by small, firm papules or plaques (resembling warts) on the sides of the hands and feet. These stationary and asymptomatic lesions appear generally at puberty, or sometimes later ## Epidemiology The prevalence is unknown. ## Differential diagnosis The histology combines hyperkeratosis and acanthosis. ## Genetic counseling Both autosomal dominant and sporadic forms have been observed. ## Management and treatment Treatment is not indicated in most patients. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Acrokeratoelastoidosis of Costa	c0545044	28,565	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=38	2021-01-23T18:45:43	{"gard": ["125"], "mesh": ["C535653"], "omim": ["101850"], "umls": ["C0545044"], "icd-10": ["Q82.8"], "synonyms": ["AKE", "PPKP3", "Punctate palmoplantar hyperkeratosis type 3", "Punctate palmoplantar keratoderma type 3"]}
This article may require cleanup to meet Wikipedia's quality standards. No cleanup reason has been specified. Please help improve this article if you can. (July 2010) (Learn how and when to remove this template message) Persistent fetal circulation Other namesPersistent pulmonary hypertension of the newborn SpecialtyPediatrics Persistent fetal circulation is a condition caused by a failure in the systemic circulation and pulmonary circulation to convert from the antenatal circulation pattern to the "normal" pattern. Infants experience a high mean arterial pulmonary artery pressure and a high afterload at the right ventricle. This means that the heart is working against higher pressures, which makes it more difficult for the heart to pump blood.[1] In a fetus, there is high pulmonary vascular resistance (PVR) and low pulmonary blood flow as the fetus does not use the lungs for oxygen transfer, but instead relies on the placenta for oxygen. When the baby is born, the lungs are needed for oxygen transfer and need high blood flow which is encouraged by low PVR. The failure of the circulatory system of the newborn to adapt to these changes by lowering PVR leads to persistent fetal circulation.[2] The newborn is therefore born with elevated PVR, which leads to pulmonary hypertension. Because of this, the condition is also widely known as persistent pulmonary hypertension of the newborn (PPHN).[3] This condition can be either acute or chronic, and is associated with significant morbidity and mortality.[1] ## Contents * 1 Presentation * 1.1 Complications * 2 Pathophysiology * 3 Diagnosis * 4 Treatment * 5 Epidemiology * 6 References * 7 Further reading * 8 External links ## Presentation[edit] ### Complications[edit] PPHN can range from mild to severe disease. In the most severe form, infants experience severe hypoxemia resulting in cardiac and pulmonary complications.[4] As a result of low oxygen levels, infants with PPHN are at an increased risk of developing complications, such as asphyxia, chronic lung disease, neurodevelopment issues, and death.[5] Nosocomial infections are another type of complication that may contribute to mortality in someone with PPHN. If the newborn acquires an infection while hospitalized, this could result in deterioration of the condition even after days of improvement.[6] ## Pathophysiology[edit] Typically, a fetus experiences pulmonary hypertension in utero since it is relying on the placenta for oxygen rather than its lungs. When the fetus is born, it is no longer attached to the placenta and must use the lungs to receive oxygen. To facilitate this change from fetus to newborn, the baby must change from a state of high PVR to low PVR, allowing for increased blood flow to circulate throughout the body.[3] This inability of the newborn to adapt to these changes is caused by various processes, such as: * Normal vascular anatomy with functional vasoconstriction: This has a good prognosis, as it is reversible. Causes include hypoxia, meconium aspiration, and respiratory distress syndrome. Left untreated, this can lead to hypoxic respiratory failure (HRF).[1] * Decreased diameter of pulmonary vessels with hypertrophy of vessel walls: This has a poor prognosis, as it is a fixed abnormality. Causes include post-term pregnancy, placental insufficiency, and NSAID use by the mother.[citation needed] * Decreased size of pulmonary vascular bed: This has a poor prognosis, as it is a fixed abnormality. It is caused by space occupying lesions such as pleural effusions and diaphragmatic hernias.[citation needed] * Functional obstruction of pulmonary blood flow: This has a good prognosis if it is reversible. Causes include polycythemia and hyperfibrinogenemia.[7] ## Diagnosis[edit] To help with diagnosis, the clinician can watch out for predisposing factors, such as: birth asphyxia, meconium aspiration, use of NSAIDs (non steroidal anti-inflammatory drugs) and SSRIs (selective serotonin reuptake inhibitors) by the mother, and early onset sepsis or pneumonia.[8] To diagnose a fetus with pulmonary hypertension, PVR must be higher than systemic vascular resistance, resulting in high afterload and decreased systemic blood flow. This causes a significant decrease in oxygen concentration, which clinically manifests as insufficient blood flow to the lower body, while there is adequate circulation to the head and right side of the body.[9] Other echocardiographic findings in PPHN include right ventricular hypertrophy, deviation of the ventricular septum, tricuspid regurgitation, and shunting at the patent foramen ovale.[3] Other clinical signs that may signify PPHN are respiratory distress, partial pressure of oxygen greater than 100 mg and elevated partial pressure of carbon dioxide.[3] A gradient of 10% or more in oxygenation saturation between simultaneous preductal and postductal arterial blood gas values in absence of structural heart disease documents persistent fetal circulation.[10] Since this may be a sign of other conditions, persistent fetal circulation must also be characterized by enlargement of right and left ventricles often confirmed through a definitive ECG.[8] Persistent fetal circulation in neonates can be reversible or irreversible depending on the classified etiology listed above. If related to pulmonary disorders, the amount of lung damage dictates whether or not treatment is efficacious in reversing newborn lung insufficiency. Other causes for acute pulmonary hypertension include: infection, endocrine disorders, and drug injury.[11] Examples of cases with newborns who with sustained fetal circulation are pulmonary hypoplasia and genetic abnormalities.[11] ## Treatment[edit] Treatment aims to increase the amount of oxygen in the blood and reverse any causes of hypoxia as well as gain adequate perfusion.[5] Common treatments include:[12] * Oxygen therapy * Mechanical ventilation * Pulmonary vasodilators * Nitrous Oxide Inhalation (iNO) * Sildenafil * Milrinone * Glucocorticoids[13] The therapies available to manage PPHN include high frequency ventilation, surfactant instillation, pulmonary vasodilators, and extracorporeal membrane oxygenation.[14] iNO is the preferred medication for PPHN due to its ability to more selectively cause pulmonary vasodilation in comparison to intravenous vasodilators. While this medication decreases the need for extracorporeal membrane oxygenation or extracorporeal life support, it has not been shown to reduce mortality. Intravenous sildenafil has been shown to have similar efficacy and is becoming more commonly used as treatment for PPHN.[15] Assessment of the efficacy of these treatments includes chest radiographs and arterial blood gases. Signs of inefficacious treatments include prolonged capillary filling time, low pulse volume, low blood pressure, and sustained metabolic acidosis.[1] In addition to treating the direct effects of this condition, other management strategies are implemented concurrently to stabilize the newborn.These include, but are not limited to nutritional support, reduction of stressful environment, gentle sedation, monitoring/treating acidosis and establishing normal systemic blood pressure.[4] Challenges in developing countries: PPHN has been seen more frequently in developing countries or resource-poor areas, though it occurs across the globe. Treating this condition often involves large interdisciplinary teams, which is not always possible in developing countries. In low-resource environments, it is recommended to focus on five main bundles of management:[16] * Increasing oxygen supply * Decreasing oxygen demand * Facilitating gas exchange * Inducing pulmonary vasodilation * Fixing metabolic disturbances ## Epidemiology[edit] It occurs in 1–2 infants per 1000 live births.[17] It is more common in males and in areas with higher altitudes.[18] Additionally, two percent of infants with respiratory distress syndrome develop PPHN.[3] ## References[edit] 1. ^ a b c d Jain A, McNamara PJ (August 2015). "Persistent pulmonary hypertension of the newborn: Advances in diagnosis and treatment". Seminars in Fetal & Neonatal Medicine. 20 (4): 262–71. doi:10.1016/j.siny.2015.03.001. PMID 25843770. 2. ^ Latham GJ, Yung D (May 2019). "Current understanding and perioperative management of pediatric pulmonary hypertension". Paediatric Anaesthesia. 29 (5): 441–456. doi:10.1111/pan.13542. PMID 30414333. 3. ^ a b c d e Mathew B, Lakshminrusimha S (July 2017). "Persistent Pulmonary Hypertension in the Newborn". Children. 4 (8): 63. doi:10.3390/children4080063. PMC 5575585. PMID 28788074. 4. ^ a b Fuloria M, Aschner JL (August 2017). "Persistent pulmonary hypertension of the newborn". Seminars in Fetal & Neonatal Medicine. 22 (4): 220–226. doi:10.1016/j.siny.2017.03.004. PMID 28342684. 5. ^ a b Pedersen J, Hedegaard ER, Simonsen U, Krüger M, Infanger M, Grimm D (October 2018). "Current and Future Treatments for Persistent Pulmonary Hypertension in the Newborn". Basic & Clinical Pharmacology & Toxicology. 123 (4): 392–406. doi:10.1111/bcpt.13051. PMID 29855164. S2CID 46918462. 6. ^ Lai MY, Chu SM, Lakshminrusimha S, Lin HC (February 2018). "Beyond the inhaled nitric oxide in persistent pulmonary hypertension of the newborn". Pediatrics and Neonatology. 59 (1): 15–23. doi:10.1016/j.pedneo.2016.09.011. PMID 28923474. 7. ^ Graves ED, Redmond CR, Arensman RM (March 1988). "Persistent pulmonary hypertension in the neonate". Chest. 93 (3): 638–41. doi:10.1378/chest.93.3.638. PMID 3277808. Archived from the original on 2014-04-24. Retrieved 2014-04-24. 8. ^ a b Sharma M, Mohan KR, Narayan S, Chauhan L (October 2011). "Persistent pulmonary hypertension of the newborn: a review". Medical Journal, Armed Forces India. 67 (4): 348–53. doi:10.1016/S0377-1237(11)60082-8. PMC 4920635. PMID 27365845. 9. ^ D'cunha C, Sankaran K (December 2001). "Persistent fetal circulation". Paediatrics & Child Health. 6 (10): 744–50. doi:10.1093/pch/6.10.744. PMC 2805987. PMID 20084150. 10. ^ Lakshminrusimha S, Kumar VH (2011-01-01). "Chapter 48 - Diseases of Pulmonary Circulation". In Fuhrman BP, Zimmerman JJ (eds.). Pediatric Critical Care (Fourth ed.). Saint Louis: Mosby. pp. 632–656. doi:10.1016/b978-0-323-07307-3.10048-5. ISBN 978-0-323-07307-3. 11. ^ a b Abman, Steven H. (2006-04-01). "Persistent Pulmonary Hypertension of the Newborn: Pathophysiology and Treatment". Advances in Pulmonary Hypertension. 5 (2): 22–30. doi:10.21693/1933-088x-5.2.22. ISSN 1933-088X. 12. ^ Luecke C, McPherson C (May 2017). "Treatment of Persistent Pulmonary Hypertension of the Newborn: Use of Pulmonary Vasodilators in Term Neonates". Neonatal Network. 36 (3): 160–168. doi:10.1891/0730-0832.36.3.160. PMID 28494828. S2CID 3917195. 13. ^ Lakshminrusimha S, Mathew B, Leach CL (April 2016). "Pharmacologic strategies in neonatal pulmonary hypertension other than nitric oxide". Seminars in Perinatology. 40 (3): 160–73. doi:10.1053/j.semperi.2015.12.004. PMC 4808469. PMID 26778236. 14. ^ Walsh MC, Stork EK (September 2001). "Persistent pulmonary hypertension of the newborn. Rational therapy based on pathophysiology". Clinics in Perinatology. 28 (3): 609–27, vii. doi:10.1016/s0095-5108(05)70109-3. PMID 11570157. 15. ^ Steinhorn RH (March 2010). "Neonatal pulmonary hypertension". Pediatric Critical Care Medicine. 11 (2 Suppl): S79-84. doi:10.1097/PCC.0b013e3181c76cdc. PMC 2843001. PMID 20216169. 16. ^ Nakwan N (December 2018). "The Practical Challenges of Diagnosis and Treatment Options in Persistent Pulmonary Hypertension of the Newborn: A Developing Country's Perspective". American Journal of Perinatology. 35 (14): 1366–1375. doi:10.1055/s-0038-1660462. PMID 29920641. S2CID 49315233. 17. ^ Chambers CD, Hernandez-Diaz S, Van Marter LJ, Werler MM, Louik C, Jones KL, Mitchell AA (February 2006). "Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn". The New England Journal of Medicine. 354 (6): 579–87. doi:10.1056/NEJMoa052744. PMID 16467545. 18. ^ D'cunha C, Sankaran K (December 2001). "Persistent fetal circulation". Paediatrics & Child Health. 6 (10): 744–50. doi:10.1093/pch/6.10.744. PMC 2805987. PMID 20084150. ## Further reading[edit] * Dunn PM (March 1994). "Professor Charles D Meigs (1792-1869) of Philadelphia and persistent fetal circulation". Archives of Disease in Childhood. Fetal and Neonatal Edition. 70 (2): F155-6. doi:10.1136/fn.70.2.f155. PMC 1061019. PMID 8154909. ## External links[edit] Classification D * ICD-10: P29.3 * ICD-9-CM: 747.83 * MeSH: D010547 * DiseasesDB: 29889 External resources * eMedicine: ped/2530 * v * t * e Conditions originating in the perinatal period / fetal disease Maternal factors complicating pregnancy, labour or delivery placenta * Placenta praevia * Placental insufficiency * Twin-to-twin transfusion syndrome chorion/amnion * Chorioamnionitis umbilical cord * Umbilical cord prolapse * Nuchal cord * Single umbilical artery presentation * Breech birth * Asynclitism * Shoulder presentation Growth * Small for gestational age / Large for gestational age * Preterm birth / Postterm pregnancy * Intrauterine growth restriction Birth trauma * scalp * Cephalohematoma * Chignon * Caput succedaneum * Subgaleal hemorrhage * Brachial plexus injury * Erb's palsy * Klumpke paralysis Affected systems Respiratory * Intrauterine hypoxia * Infant respiratory distress syndrome * Transient tachypnea of the newborn * Meconium aspiration syndrome * Pleural disease * Pneumothorax * Pneumomediastinum * Wilson–Mikity syndrome * Bronchopulmonary dysplasia Cardiovascular * Pneumopericardium * Persistent fetal circulation Bleeding and hematologic disease * Vitamin K deficiency bleeding * HDN * ABO * Anti-Kell * Rh c * Rh D * Rh E * Hydrops fetalis * Hyperbilirubinemia * Kernicterus * Neonatal jaundice * Velamentous cord insertion * Intraventricular hemorrhage * Germinal matrix hemorrhage * Anemia of prematurity Gastrointestinal * Ileus * Necrotizing enterocolitis * Meconium peritonitis Integument and thermoregulation * Erythema toxicum * Sclerema neonatorum Nervous system * Perinatal asphyxia * Periventricular leukomalacia Musculoskeletal * Gray baby syndrome * muscle tone * Congenital hypertonia * Congenital hypotonia Infections * Vertically transmitted infection * Neonatal infection * rubella * herpes simplex * mycoplasma hominis * ureaplasma urealyticum * Omphalitis * Neonatal sepsis * Group B streptococcal infection * Neonatal conjunctivitis Other * Miscarriage * Perinatal mortality * Stillbirth * Infant mortality * Neonatal withdrawal * v * t * e Congenital vascular defects / Vascular malformation Great arteries/ other arteries Aorta * Patent ductus arteriosus * Coarctation of the aorta * Interrupted aortic arch * Double aortic arch * Right-sided aortic arch * Overriding aorta * Aneurysm of sinus of Valsalva * Vascular ring Pulmonary artery * Pulmonary atresia * Stenosis of pulmonary artery Subclavian artery * Aberrant subclavian artery Umbilical artery * Single umbilical artery Great veins Superior/inferior vena cava * Congenital stenosis of vena cava * Persistent left superior vena cava Pulmonary vein * Anomalous pulmonary venous connection (Total, Partial) * Scimitar syndrome Arteriovenous malformation * Cerebral arteriovenous malformation [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Persistent fetal circulation	c0031190	28,566	wikipedia	https://en.wikipedia.org/wiki/Persistent_fetal_circulation	2021-01-18T18:47:39	{"mesh": ["D010547"], "umls": ["C0031190"], "wikidata": ["Q7170410"]}
Shield et al. (1992) reported 4 patients and their extended families comprising 17 cases, all of whom had congenital exfoliative erythroderma resistant to treatment, associated with failure to thrive and hypoalbuminemia. All died in the first year of life. Three of the families had recognized consanguinity. In the fourth family, the parents were said to be nonconsanguineous but were a Turkish Cypriot couple coming from the same village. Other families were Turkish, Omani, and Pakistani. The erythroderma dated from birth, with no obvious nail or hair-shaft abnormalities. Growth \- Failure to thrive \- Hypoalbuminemia Misc \- Infantile death \- No obvious nail or hair-shaft abnormalities Inheritance \- Autosomal recessive Skin \- Congenital exfoliative erythroderma ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	ERYTHRODERMA, LETHAL CONGENITAL	c1856898	28,567	omim	https://www.omim.org/entry/227090	2019-09-22T16:28:07	{"mesh": ["C535513"], "omim": ["227090"], "orphanet": ["1954"]}
A rare, genetic, syndromic intellectual disability characterized by severe intellectual disability, distinctive craniofacial features and variable multiple congenital anomalies including ocular, brain, urogenital and skeletal abnormalities. ## Epidemiology To date, 19 molecularly diagnosed cases have been described in the scientific and medical literature. ## Clinical description The most prominent clinical findings are severe intellectual disability, pre-and postnatal growth retardation, microcephaly, and typical craniofacial features which include non-progressive microcephaly of prenatal onset, prominence of the zygomatic region of the face, full cheeks, prominent frontal tubers, sparse and arched eyebrows, blepharophimosis with epicanthal folds, upslanted palpebral fissures, preauricular skin tags, underdeveloped and abnormally folded ears, wide nasal base, low nasal bridge, anteverted nares, long and flat philtrum and retrognathia. Hypotonia, feeding difficulties, failure to thrive and poor speech development are universal findings. Many patients require tube-feeding. Perceptive language is better than expressive, some patients acquire a few words and basic ambulation skills such as eating and dressing independently. Brain abnormalities may include absent or hypoplastic corpus callosum and changes in white matter signal intensity on MRI, but major structural brain malformations are absent. Epilepsy may occur. Ocular abnormalities include short and narrow palpebral fissures, microcornea/microphtalmos, refractive errors and strabismus. Other less frequently observed congenital anomalies include hearing loss, urogenital abnormalities (hypoplastic external genitals, hypospadias, vesicoureteral reflux, duplicated renal pelvis), skeletal abnormalities (including clinodactyly, hypoplastic or absent distal phalanges of some digits, pectus carinatum, coxa valga, pes talus varus and scoliosis). Ectodermal anomalies include thin, sparse hair, and light colored, fine skin. Gastroesophageal reflux is a frequent problem. Congenital heart malformations and breathing problems (tracheo/laryngomalacia, subglottic stenosis) are frequent. About half of patients have abnormal cholesterol levels (low total HDL/LDL levels). Patients have an overall friendly disposition. ## Etiology The syndrome is caused by biallelic inactivating mutations in the UBE3B gene (12q24.11), which encodes ubiquitin protein ligase E3B, a putative calmodulin-regulated mitochondria-associated enzyme involved in the protein ubiquitination pathway. ## Diagnostic methods Diagnosis is established in a proband with developmental delay/intellectual disability, characteristic craniofacial anomalies and biallelic UBE3B pathogenic variants. ## Differential diagnosis Differential diagnosis principally includes other syndromes featuring association of blepharophimosis and intellectual disability (e.g. blepharophimosis-intellectual disability syndrome, Maat-Kievit Brunner type), as well as Toriello-Carey syndrome, Smith-Lemli-Opitz syndrome, and DOORS syndrome (Deafness, Onychodystrophy, Osteodystrophy, Mental Retardation and Seizures) if digital anomalies are present. ## Antenatal diagnosis Prenatal testing for at risk pregnancies is possible where the UBE3B pathogenic variants have been identified previously in a family member. ## Genetic counseling Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them that there is a 25% risk of having an affected child at each pregnancy. ## Management and treatment Full multisystem evaluation should be performed following the diagnosis, and growth, developmental progress, vision, hearing and contractures/scoliosis should be regularly followed up. Educational intervention and speech therapy should start as early as possible. Intervention for feeding problems may be needed. Treatment of the encountered congenital and functional anomalies is standard. ## Prognosis Prognosis depends on the severity of symptoms; however, data is limited. * European Reference Network [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Oculocerebrofacial syndrome, Kaufman type	c1855663	28,568	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2707	2021-01-23T18:22:27	{"gard": ["3084"], "mesh": ["C537013"], "omim": ["244450"], "umls": ["C1855663"], "icd-10": ["Q87.0"]}
A number sign (#) is used with this entry because of evidence that caudal duplication anomaly is associated with hypermethylation of the AXIN1 promoter (603816). One such patient has been reported. Clinical Features Dominguez et al. (1993) used the term caudal duplication syndrome to describe the occurrence of duplications of different organs in the caudal region. They reported 6 affected patients and reviewed 8 similar previously published cases. Kroes et al. (2002) described 2 unrelated patients with caudal duplication anomaly. The first patient, a girl who had an unaffected monozygotic twin sister, presented with a duplication of the distal spine from L4, left double ureter, duplication of the vagina and cervix, and duplication of the distal colon. Her psychomotor development was normal at age 1.5 years. The second patient was diagnosed with a duplication of the colon, bladder, vagina, and uterus. Her mental development and growth were normal at age 12 years. Pathogenesis Kroes et al. (2002) discussed possible causes of the caudal duplication anomaly, including polytopic primary developmental field defects, disruptive sequences, and somatic or germline mutations in certain developmental genes. Molecular Genetics Kroes et al. (2002) noted that 2 genetic mouse models, 'fused' and 'disorganization,' show some resemblance to the caudal duplication anomaly. Because 'fused' results from mutations in the axin gene (603816), they performed DNA analysis of the AXIN1 gene in 1 of their patients and her family but detected no causative mutation. Caudal duplication anomaly is similar to an anomaly seen in Axin(Fu) mice, which carry a mutation in the Axin locus (Vasicek et al., 1997). Affected mice display bifurcated tails as a result of caudal duplication in the distal region. Axin encodes an inhibitor of the Wnt-signaling pathway and has been shown to regulate embryonic axis formation in mouse and in Xenopus (Zeng et al., 1997). Suppression of wildtype Axin in Xenopus embryos results in the duplication of the body axis. It had been suggested that stochastically or environmentally triggered differences in the epigenetic status of key genes may be responsible for some phenotypic discordance between monozygotic (MZ) twins and, indeed, for much of the burden of complex disease. Using bisulfite sequencing, Oates et al. (2006) examined methylation at the promoter region of the AXIN1 gene in the MZ twins discordant for a caudal duplication anomaly in whom no causative AXIN1 mutation was found (Kroes et al., 2002) and in age-related singleton controls. Methylation of the promoter region in peripheral blood mononuclear cells was variable among individuals, including MZ pairs. In the MZ pair discordant for the caudal duplication, this region of the affected twin was significantly more methylated (603816.0002) than that of the unaffected twin (P less than 0.0001), which was significantly more methylated than those of the controls (P = 0.02). Oates et al. (2006) confirmed that this CpG island functions as a promoter in vitro and that its activity is inversely proportional to the extent of methylation. This finding raised the possibility that hypermethylation of the AXIN1 promoter, by mechanisms as yet undetermined, is associated with the malformation. The authors suggested that this case may be paradigmatic for some cases of MZ discordance. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	CAUDAL DUPLICATION ANOMALY	c1842884	28,569	omim	https://www.omim.org/entry/607864	2019-09-22T16:08:39	{"mesh": ["C564315"], "omim": ["607864"], "orphanet": ["1756"]}
Adrenal cancer is a rare form of cancer that occurs due to abnormal and uncontrolled cell growth in the adrenal glands (small glands that sit above each kidney). There are three different types of adrenal cancer which vary by location and the age at which they are often diagnosed: * Adrenocortical carcinoma \- The most common type of adrenal cancer which develops in the adrenal cortex (the outer part of the adrenal gland) * Neuroblastoma \- A childhood cancer that begins in the adrenal medulla (the inner part of the adrenal gland) * Pheochromocytoma \- A neuroendocrine tumor that begins in the adrenal medulla The signs and symptoms associated with the condition largely depend on if the cancer is 'functioning' (producing hormones) or 'nonfunctioning' (not producing hormones) and which hormones are present in excess. In most cases, the underlying cause of the condition is unknown. However, certain genetic conditions such as multiple endocrine neoplasia type 2, Li-Fraumeni syndrome, Von Hippel-Lindau syndrome, neurofibromatosis type I, and Carney complex are associated with an increased risk of developing adrenal tumors and cancer. Treatment may include a combination of surgery, hormone therapy, chemotherapy and radiation therapy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Adrenal cancer	c0750887	28,570	gard	https://rarediseases.info.nih.gov/diseases/5751/adrenal-cancer	2021-01-18T18:02:15	{"mesh": ["D000310"], "umls": ["C0750887"], "synonyms": []}
A number sign (#) is used with this entry because of evidence that immunodeficiency-41 (IMD41) with lymphoproliferation and autoimmunity is caused by homozygous or compound heterozygous mutation in the IL2RA gene (147730) on chromosome 10p15. Description Immunodeficiency-41 is an autosomal recessive complex disorder of immune dysregulation. Affected individuals present in infancy with recurrent viral, fungal, and bacterial infections, lymphadenopathy, and variable autoimmune features, such as autoimmune enteropathy and eczematous skin lesions. Immunologic studies show a defect in T-cell regulation (summary by Goudy et al., 2013). Clinical Features Sharfe et al. (1997) described a novel human immune aberration arising from a truncation mutation of the interleukin-2 receptor alpha chain (CD25), a subunit of the tripartite high-affinity receptor for interleukin-2. This immunodeficiency was characterized by decreased numbers of peripheral T cells displaying abnormal proliferation but normal B-cell development. Extensive lymphocytic infiltration of tissues, including lung, liver, gut, and bone, was observed, accompanied by tissue atrophy and inflammation. Although mature T cells were present, the absence of CD25 affected the differentiation of thymocytes. While displaying normal development of CD2 (186990), CD3 (186790), CD4 (186940), and CD8 (186910) expression, CD25-deficient cortical thymocytes did not express CD1 (188370); furthermore, they failed to downregulate levels of antiapoptotic protein BCL2 (151430). The patient was a male child of first-cousin parents with a history of increased susceptibility to viral, bacterial, and fungal infections. He presented at the age of 6 months with cytomegalovirus (CMV) pneumonitis, persistent oral thrush, and Candida esophagitis. He also had adenovirus gastroenteritis, developed chronic diarrhea, and failed to thrive. From the age of 8 months, lymphadenopathy and hepatosplenomegaly became increasingly apparent, with no significant abnormality of liver function, however. He subsequently required hospitalization for recurrent exacerbation of lung disease. By the age of 3 years he had developed gingivitis, iron deficiency anemia with no evidence of hemolytic anemia, chronic inflammation of the mandible, and chronic lung disease involving the right upper lobe. Severe immunologic dysfunction was proven by the patient's inability to reject an allogeneic skin graft. Consequently the patient underwent an allogeneic bone marrow transplant following cytoreduction. Engraftment was rapid and a complete resolution of symptoms ensued. Roifman (2000) performed additional studies on thymic tissue from the patient reported by Sharfe et al. (1997). They found that the markedly reduced apoptosis in the thymus resulted in expansion of autoreactive clones in multiple tissues. Caudy et al. (2007) reported an 8-year-old boy with a complex immunologic disorder. He presented at age 6 weeks with diarrhea, insulin-dependent diabetes mellitus, and respiratory insufficiency due to CMV infection. During childhood, he developed autoimmune enteropathy with villous atrophy, eczema, lymphadenopathy, hepatosplenomegaly, hypothyroidism, autoimmune hemolytic anemia, and autoimmune granulocytopenia. He had recurrent infections, including Epstein-Barr virus (EBV) infection. The clinical features were reminiscent of IPEX (304790), but FOXP3 (300292) expression was normal on patient CD4+ T lymphocytes. Immunologic studies showed that the patient's cells failed to express detectable IL10 (124092) in response to IL2 (147680), suggesting a defect in the IL2 receptor. Caudy et al. (2007) noted that since IL10 is able to inhibit naive T-cell proliferation, absence of IL10 as seen in this patient was consistent with the complex features of immune dysregulation. Goudy et al. (2013) reported an 8-year-old girl, born of consanguineous Italian parents, with early-onset recurrent viral, bacterial, and fungal infections, CMV infection, lymphadenopathy, and various autoimmune disorders, including autoimmune enteropathy, autoimmune thyroiditis, eczema, psoriasiform dermatitis, and alopecia. Skin biopsy showed an infiltration of CD8+ T lymphocytes. Immunologic studies showed alterations of the peripheral T-cell compartment, with a skew toward increased CD8+ T cells over CD4+ T cells and expansion of memory T cells. There were also low levels of NK and B cells. In vitro studies showed poor T-cell proliferative responses to polyclonal mitogens, fungi, and viruses. The findings were consistent with a lack of effective antigen-specific T-cell responses combined with cytokine-driven polyclonal T-cell proliferation and activation that mediated tissue damage. Bezrodnik et al. (2014) reported a 5-year-old adopted girl from Argentina who presented in the first week of life with severe atopic dermatitis, chronic diarrhea, and severe respiratory infections. She later developed alopecia, severe varicella infection, and chronic pneumonia necessitating permanent oxygen therapy. At age 4, she had severely compromised lung parenchyma with follicular bronchiolitis and lymphocyte hyperplasia on lung biopsy. Immunologic workup showed hypergammaglobulinemia, absent IgG4, and impaired specific polysaccharide response. Regulatory T cells were extremely low, memory B cells were decreased, and activated CD4+ T cells showed no CD25 upregulation. Antinuclear antibodies were also present, but the patient did not have significant features of autoimmune disorders. Inheritance The transmission pattern of IMD41 in the families reported by Caudy et al. (2007) and Goudy et al. (2013) was consistent with autosomal recessive inheritance. Molecular Genetics In a patient with IL2RA deficiency, Sharfe et al. (1997) identified a homozygous 4-bp deletion in the CD25 gene, resulting in a frameshift in protein translation (147730.0001). In an 8-year-old Caucasian boy with IMD41, Caudy et al. (2007) identified compound heterozygous truncating mutations in the IL2RA gene (147730.0004 and 147730.0005). Each unaffected parent was heterozygous for 1 of the mutations. In an 8-year-old girl, born of consanguineous Italian parents, with IMD41, Goudy et al. (2013) identified a homozygous missense mutation in the IL2RA gene (S166N; 147730.0006). Each unaffected parent was heterozygous for the mutation. Patient CD4+ T cells showed absence of surface IL2RA expression, consistent with a loss of function. However, IL2RA was detected within the cytoplasm of the patient's T cells, suggesting that the mutation inhibits membrane expression. Additional functional studies of the variant were not performed. In an adopted 5-year-old girl from Argentina with IMD41, Bezrodnik et al. (2014) identified a homozygous missense mutation in the IL2RA gene (Y41S; 147730.0007). Functional studies of the variant were not performed, but patient CD4+ T lymphocytes did not show upregulation of IL2RA upon activation. INHERITANCE \- Autosomal recessive RESPIRATORY \- Recurrent respiratory infections Lung \- Inflammatory lung disease \- Lymphocytic infiltration ABDOMEN Liver \- Hepatomegaly Spleen \- Splenomegaly Gastrointestinal \- Autoimmune enteropathy \- Chronic diarrhea \- Villous atrophy SKIN, NAILS, & HAIR Skin \- Eczema \- Dermatitis Hair \- Alopecia ENDOCRINE FEATURES \- Diabetes mellitus (in some patients) \- Hypothyroidism (in some patients) HEMATOLOGY \- Autoimmune hemolytic anemia IMMUNOLOGY \- Recurrent viral, bacterial, and fungal infections \- Immunodeficiency \- Lymphadenopathy \- Increased nonspecific CD8+ T-cell proliferation \- Poor antigen specific T-cell proliferation \- Autoimmune disorders (in some patients) \- Susceptibility to EBV and CMV infections \- Defective IL10 production by T cells MISCELLANEOUS \- Onset in early infancy \- Autoimmune features are variable \- Four unrelated patients have been reported (last curated July 2015) MOLECULAR BASIS \- Caused by mutation in the interleukin 2 receptor, alpha gene (IL2RA, 147730.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	IMMUNODEFICIENCY 41 WITH LYMPHOPROLIFERATION AND AUTOIMMUNITY	c1853392	28,571	omim	https://www.omim.org/entry/606367	2019-09-22T16:10:28	{"mesh": ["C565232"], "omim": ["606367"], "orphanet": ["169100"], "synonyms": ["Interleukin-2 receptor alpha chain deficiency", "Alternative titles", "INTERLEUKIN 2 RECEPTOR, ALPHA, DEFICIENCY OF", "CD25 DEFICIENCY", "IL2RA DEFICIENCY"]}
Miyoshi myopathy is a type of muscular dystrophy characterized by muscle weakness and atrophy (wasting), mainly in the distal parts of the legs. The first symptoms typically begin in young adulthood (on average 20 years of age) and include weakness and atrophy of the calves (sometimes asymmetrically), leading to inability to jump, run or walk on tiptoes. Over a period of years, the weakness and atrophy typically spread to the thighs and gluteal muscles. The forearms may become mildly atrophic with decrease in grip strength. Blood exams show an elevation of the creatine kinase (CK) often 10-100 times above the normal values. It is caused by variations (mutations) in the DYSF gene. Inheritance is autosomal recessive. Management may include physical therapy, use of mechanical aids, surgical intervention for orthopedic complications, respiratory aids, and social and emotional support. Miyoshi myopathy is part of the group of diseases known as "Dysferlinopathies", which are caused by DYSF pathogenic variants. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Miyoshi myopathy	c1850808	28,572	gard	https://rarediseases.info.nih.gov/diseases/9676/miyoshi-myopathy	2021-01-18T17:59:01	{"omim": ["254130", "613318", "613319"], "orphanet": ["45448"], "synonyms": ["Muscular dystrophy, distal, late onset, autosomal recessive", "MM", "Miyoshi distal myopathy"]}
## Clinical Features Martinez et al. (2001) reported a 4-generation family in which 5 males had mild to moderate nonspecific mental retardation. Brain CT scan performed in 1 patient was normal. Inheritance The pedigree pattern in the family with mental retardation reported by Martinez et al. (2001) was consistent with X-linked inheritance. Mapping By typing of markers throughout the X chromosome in a 4-generation family with nonsyndromic mental retardation, Martinez et al. (2001) mapped the phenotype locus to a 2-cM interval between markers DXS8019 and DXS365 on chromosome Xp22.2. Molecular Genetics ### Exclusion Studies In a family with nonsyndromic mental retardation mapping to Xp22.2, Martinez et al. (2001) performed direct sequencing of the RSK2 gene (300075) but found no causal mutation. They concluded that another unidentified gene for X-linked mental retardation is located near RSK2. INHERITANCE \- X-linked recessive HEAD & NECK Face \- Synophrys, mild NEUROLOGIC Central Nervous System \- Mental retardation, mild to moderate \- Normal brain CT Behavioral Psychiatric Manifestations \- Outgoing personality without autistic traits MISCELLANEOUS \- One 4-generation family with 5 affected males has been reported (last curated May 2016) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	MENTAL RETARDATION, X-LINKED 73	c2931498	28,573	omim	https://www.omim.org/entry/300355	2019-09-22T16:20:24	{"doid": ["0050776"], "mesh": ["C567906"], "omim": ["300355"], "orphanet": ["777"]}
Pseudocholinesterase deficiency is a condition that causes increased sensitivity to certain muscle relaxant drugs used during general anesthesia (choline esters). These drugs relax the muscles used for movement, including those used for breathing. Normally, the muscles are able to move again a few minutes after the drugs are given. People with pseudocholinesterase deficiency may not be able to move or breathe on their own for a few hours after these drugs are given. They therefore may need mechanical ventilation until the drugs are cleared from the body. People with this condition may also have increased sensitivity to other types of drugs as well as to some agricultural pesticides. Pseudocholinesterase deficiency can be inherited (genetic) or acquired. When it is inherited, it is autosomal recessive and caused by mutations in the BCHE gene. Acquired pseudocholinesterase deficiency may have various causes such as chronic infection, kidney or liver disease, malnutrition, major burns, cancer, or various medications. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Pseudocholinesterase deficiency	c1283400	28,574	gard	https://rarediseases.info.nih.gov/diseases/7482/pseudocholinesterase-deficiency	2021-01-18T17:58:05	{"mesh": ["C537417"], "omim": ["177400"], "orphanet": ["132"], "synonyms": ["Succinylcholine Sensitivity", "Apnea, Postanesthetic", "Cholinesterase 2 Deficiency", "Pseudocholinesterase E1", "Suxamethonium Sensitivity", "Butyrylcholinesterase deficiency"]}
Cystitis glandularis at trigone This article may be confusing or unclear to readers. Please help us clarify the article. There might be a discussion about this on the talk page. (January 2010) (Learn how and when to remove this template message) Cystitis glandularis is the transformation of mucosal cells lining the urinary bladder. They undergo glandular metaplasia, a process in which irritated tissues take on a different form, in this case that of a gland.[1] The main importance is in the findings of test results, in this case histopathology. They must distinguish a benign metaplastic change from the cancerous condition urothelial cell carcinoma.[2] It is a very common finding in bladder biopsies and cystectomies, and most often found in the trigone area. Cystitis glandularis lesions are usually present as small microscopic foci; however, occasionally it can form raised intramucosal or polypoid lesions. The cystitis glandularis lesions are within the submucosa. ## Contents * 1 Types * 2 Related lesions * 3 References * 4 Further reading ## Types[edit] There are two main types of cystitis glandularis, non-mucinous and mucinous (intestinal). The difference is in the cellular production of mucin, a normal feature of colonic and intestinal epithelial cells but not of urothelial cells. Another distinction is made between focal areas and diffuse involvement of the bladder. Whereas focal areas are more common, diffuse involvement is seen in chronically irritated bladders, such as in paraplegics or those with bladder stones or indwelling catheters. Individuals with diffuse intestinal-type cystitis glandularis are at increased risk for developing bladder cancer. ## Related lesions[edit] Cystitis glandularis arises from and merges with Von Brunn's nests, which are groups of urothelial cells (cells of urinary tract) within the lamina propria and submucosa, formed from budding from the surface mucosa. They are considered normal. Cystitis cystica is a similar lesion to cystitis glandularis, where the central area of the Von Brunn's nests have degenerated, leaving cystic lesions. Other metaplastic entities in the urinary bladder include squamous metaplasia and nephrogenic adenoma. ## References[edit] 1. ^ Yi X, Lu H, Wu Y, Shen Y, Meng Q, Cheng J, Tang Y, Wu F, Ou R, Jiang S, Bai X, Xie K (October 2014). "Cystitis glandularis: A controversial premalignant lesion". Oncology Letters. 8 (4): 1662–1664. doi:10.3892/ol.2014.2360. PMC 4156188. PMID 25202387. 2. ^ "Cystitis Glandularis - American Urological Association". www.auanet.org. Retrieved 2019-05-06. ## Further reading[edit] * Bostwick DG, Cheng L (2008). "Cystitis cystica and cystitis glandularis". Urologic Surgical Pathology (2nd ed.). Mosby Elsevier. ISBN 978-0-323-07614-2. Wikimedia Commons has media related to Cystitis glandularis. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Cystitis glandularis	c0268837	28,575	wikipedia	https://en.wikipedia.org/wiki/Cystitis_glandularis	2021-01-18T18:53:47	{"umls": ["C0268837"], "wikidata": ["Q5201263"]}
A number sign (#) is used with this entry because primary microcephaly-1 (MCPH1) is caused by homozygous mutation in the gene encoding microcephalin (MCPH1; 607117) on chromosome 8p23. Description Primary microcephaly refers to the clinical finding of a head circumference more than than 3 standard deviations (SD) below the age- and sex-related mean, present at birth. Primary microcephaly is a static developmental anomaly, distinguished from secondary microcephaly, which refers to a progressive neurodegenerative condition. Microcephaly is a disorder of fetal brain growth; individuals with microcephaly have small brains and almost always have mental retardation, although rare individuals with mild microcephaly (-3 SD) and normal intelligence have been reported. Additional clinical features may include short stature or mild seizures. MCPH is associated with a simplification of the cerebral cortical gyral pattern and a slight reduction in the volume of the white matter, consistent with the small size of the brain, but the architecture of the brain in general is normal, with no evidence of a neuronal migration defect (review by Woods et al., 2005). Most cases of primary microcephaly show an autosomal recessive mode of inheritance. Because MCPH directly affects neurogenesis, or neurogenic mitosis, rather than growth of the skull, some prefer the term 'micrencephaly' (Hofman, 1984). MCPH1 in particular is associated with premature chromosome condensation in cell studies (Darvish et al., 2010). ### Genetic Heterogeneity of Primary Microcephaly Primary microcephaly is a genetically heterogeneous disorder. See MCPH2 (604317), caused by mutation in the WDR62 gene (613583) on chromosome 19q13; MCPH3 (604804), caused by mutation in the CDK5RAP2 gene (608201) on 9q33; MCPH4 (604321), caused by mutation in the CASC5 gene (609173) on 15q14; MCPH5 (608716), caused by mutation in the ASPM gene (605481) on 1q31; MCPH6 (608393), caused by mutation in the CENPJ gene (609279) on 13q12; MCPH7 (612703), caused by mutation in the STIL gene (181590) on 1p33; MCPH8 (614673), caused by mutation in the CEP135 gene (611423) on 4q12; MCPH9 (614852), caused by mutation in the CEP152 gene (613529) on 15q21; MCPH10 (615095), caused by mutation in the ZNF335 gene (610827) on 20q13; MCPH11 (615414), caused by mutation in the PHC1 gene (602978) on 12p13; MCPH12 (616080), caused by mutation in the CDK6 gene (603368) on 7q21; MCPH13 (616051), caused by mutation in the CENPE gene (117143) on 4q24; MCPH14 (616402), caused by mutation in the SASS6 gene (609321) on 1p21; MCPH15 (616486), caused by mutation in the MFSD2A gene (614397) on 1p34; MCPH16 (616681), caused by mutation in the ANKLE2 gene (616062) on 12q24; MCPH17 (617090), caused by mutation in the CIT gene (605629) on 12q24; MCPH18 (617520), caused by mutation in the WDFY3 gene (617485) on 4q21; and MCPH19 (617800), caused by mutation in the COPB2 gene (606990) on 3q23; MCPH20 (617914), caused by mutation in the KIF14 gene (611279) on 1q31; MCPH21 (617983), caused by mutation in the NCAPD2 gene (615638) on 12p13; MCPH22 (617984), caused by mutation in the NCAPD3 gene (609276) on 11q25; MCPH23 (617985), caused by mutation in the NCAPH gene (602332) on 2q11; MCPH24 (618179), caused by mutation in the NUP37 gene (609264) on 12q23; and MCPH25 (618351), caused by mutation in the MAP11 gene (618350) on 7q22. Clinical Features Primary or true microcephaly is different from microcephaly secondary to degenerative brain disorder (Cowie, 1960). In true microcephaly, there is no neurologic defect, other than mental deficiency, and no skeletal or other malformation. The differentiation of primary and secondary microcephaly was investigated by Qazi and Reed (1973). In a biometric analysis of brain size of micrencephalics compared to normal controls, Hofman (1984) found that micrencephalics have a significantly lower brain weight in adolescence than in early childhood, and that this cerebral dystrophy continues throughout adulthood, leading to death in more than 85% of males and 78% of females before age 30 years. Since this decline in brain weight is not accompanied by a similar reduction in head circumference, the brains of elderly micrencephalic individuals no longer occupy the entire cranial cavity. Hofman (1984) concluded that head circumference is an unsuitable parameter for estimating brain size in micrencephaly. Mikati et al. (1985) reported microcephaly associated with short stature and mental retardation in 3 brothers and a sister out of 9 children of first-cousin parents. Hypergonadotropic hypogonadism and a variety of minor anomalies were also present. Tolmie et al. (1987) described the clinical and genetic findings of a series of microcephalic patients referred to the Genetic Counselling Service for the West of Scotland. There were 29 isolated cases and 9 families with recurrent microcephaly. The sib recurrence risk of 19% was taken to reflect the high incidence of autosomal recessive microcephaly. In this series, there appeared to be several varieties of recessive microcephaly. The most frequent, affecting 5 sib pairs, was associated with spastic quadriplegia, seizures, and profound mental handicap. In 15 families with 1 microcephalic child, prenatal diagnosis by serial ultrasound scans was undertaken in 21 subsequent pregnancies. Four recurrences were detected in the third trimester and 1 recurrence was missed because no scan was performed after 24 weeks gestation when the ultrasound measurements indicated satisfactory head growth. The main reason for late diagnosis was that head growth did not slow appreciably until the last trimester. Although Qazi and Reed (1975) stated that carriers of primary microcephaly have diminished intelligence, Pattison et al. (2000) noted that this had not been seen in any of the families in with linkage to specific MCPH loci had been reported. Bond et al. (2005) emphasized that MCPH is evident at birth, with head circumference ranging between 4 and 12 standard deviations below the mean and thereafter remaining proportionately small with age. Cognitive functions are reduced, but epilepsy and other neurologic disorders or decline are rarely reported, and motor skills are preserved. It is hypothesized that neuronal precursor cells in the neuroepithelium are affected, resulting in reduced production of functional neurons during fetal life. Darvish et al. (2010) reported 8 unrelated consanguineous families from Iran with primary microcephaly-1. Head circumference of affected individuals ranged from -3 to -11 SD, and mental retardation ranged from mild to severe. Karyotype analysis of 1 affected individual from each family showed curly chromosomes with a high level of breakage. There were also increased numbers of prophase looking cells (80%), compared to control (13%). The features were consistent with premature chromosome condensation. Tommerup et al. (1993) reported a Danish girl, born of consanguineous parents, with microcephaly, craniosynostosis, ptosis, bird-like facies with micrognathia, and moderate mental retardation, associated with a highly increased frequency of spontaneous chromosome breakage. In addition, unique cellular features included endomitosis and hypersensitivity to clastogenic agents as observed in phytohemagglutinin-stimulated peripheral lymphocytes. Both the alkylating agent Trenimon and the radiomimetic drug bleomycin produced an abnormal frequency of changes. Abnormal chromosomal spiralization and some aspects of abnormal cellular division were also observed. In the patient reported by Tommerup et al. (1993), Farooq et al. (2010) identified a homozygous truncating mutation in the MCPH1 gene (S101X; 607117.0007), thus widening the phenotypic spectrum of MCPH1-related diseases. Biochemical Features Neitzel et al. (2002) reported 2 sibs, born of consanguineous parents, with microcephaly, growth retardation, and severe mental retardation. Chromosome analysis showed a high frequency of prophase-like cells (more than 10%) in lymphocytes, fibroblasts, and lymphoblast cell lines, with an otherwise normal karyotype. Pulse-labeling with (3)H-thymidine and autoradiography showed that, 2 hours after the pulse, 28 to 35% of the prophases were labeled, compared with 9 to 11% in healthy control subjects, indicating that the phenomenon is due to premature chromosome condensation in the early G2 phase. Flow cytometry studies showed that the cell cycle was not prolonged and compartment sizes did not differ from controls. There was also no increased reaction of the cells to X irradiation or to the clastogens bleomycin and mitomycin C, in contrast to results in the cell-cycle mutants ataxia-telangiectasia (208900) and Fanconi anemia (FANCA; 227650). The rates of sister chromatid exchanges and the mitotic nondisjunction rates were 'inconspicuous.' Premature entry of cells into mitosis suggested that mutation in a gene involved in cell-cycle regulation. Neitzel et al. (2002) pointed out that in mammals there is only 1 description of an in vitro mutation (in a hamster cell line) that undergoes premature chromosome condensation at a nonpermissive temperature (Kai et al., 1986; Uchida et al., 1990). This mutation is complemented by the human RCC1 gene (179710). On the basis of homozygosity mapping with highly polymorphic microsatellite DNA markers flanking RCC1 on human 1q36.1, Neitzel et al. (2002) excluded RCC1 as a candidate for the premature chromosome condensation in the sibs they studied. A number of other candidate genes were excluded. Inheritance Primary microcephaly is usually inherited as an autosomal recessive trait. Kloepfer et al. (1964) reported an extensive pedigree segregating microcephaly in an autosomal recessive pattern. Mapping Jackson et al. (1998) mapped a locus for a form of primary microcephaly, MCPH1, to chromosome 8p23 by homozygosity mapping of 2 consanguineous Pakistani families. Their results indicated that the gene lies within a 13-cM region between markers D8S1824 and D8S1825 (maximum multipoint lod score = 8.1 at D8S277). Molecular Genetics In 2 families with primary microcephaly sharing an ancestral 8p23 haplotype, Jackson et al. (2002) identified a homozygous mutation in the microcephalin gene (S25X; 607117.0001). All 7 affected individuals were homozygous for the mutation, and their 8 unaffected parents were heterozygous for the mutation. In the 2 sibs from the family with microcephaly and premature chromosome condensation originally reported by Neitzel et al. (2002), Trimborn et al. (2004) identified a homozygous 1-bp insertion, 427insA, in the MCPH1 gene (607117.0002). The mutation was present in heterozygous state in the parents and was not present in 220 control alleles. In 6 affected members of a consanguineous Iranian family with mental retardation, mild microcephaly, and premature chromosome condensation in at least 10 to 15% of cells, Garshasbi et al. (2006) identified a homozygous deletion in the MCPH1 gene (607117.0003). Short stature was also a feature in the 2 affected females. Darvish et al. (2010) identified 8 different homozygous mutations in the MCPH1 gene (see, e.g., 607117.0004-607117.0006) in 8 (8.7%) of 112 Iranian families with primary microcephaly, mental retardation, and premature chromosome condensation. Six of the mutations were predicted to result in a truncated protein. One of the families and the corresponding mutation had been reported by Garshasbi et al. (2006). Pathogenesis Bond et al. (2005) noted that the ASPM, CDK5RAP2, and CENPJ genes, each of which is mutant in a form of MCPH, encode proteins that are centrosomal components during mitosis, which emphasized the key role of the centrosome in each major stage of the development and function of the nervous system. Population Genetics In the Netherlands, the frequency of true microcephaly was placed at about 1 in 250,000 by Van den Bosch (1959). Scala et al. (2010) found no mutations in the MCPH1 gene in a large cohort of nonconsanguineous patients with microcephaly who did not have mutations in the ASPM gene (605481). The cohort included 81 unrelated patients (78% Caucasian, 16% Arab, 6% other). Thirty-four patients met the strict MCPH criteria of congenital microcephaly at least -4 SD, mental retardation, and no brain malformations; 47 patients met the expanded criteria of microcephaly -2 to -3 SD, possible brain malformations, and borderline-to-normal intellectual function. In each group, about 19% had borderline mental retardation and about 23% had seizures. The findings indicated that MCPH1 mutations are not common in populations with a low prevalence of consanguinity. History Microcephaly can result from exposure of the human fetus to x-rays (Plummer, 1952). Rizzo and Pavone (1995) described a brother and sister with severe microcephaly associated with small ears, markedly protruding midface, curved nose, and pronounced retrognathia. The brother had borderline/normal intelligence, episodic seizures, and clumsiness; the sister had a normal IQ and neither seizures nor behavioral abnormalities. The authors concluded that this condition was separate and distinct from autosomal recessive microcephaly, the so-called microcephalia vera, because of the normal or near-normal intelligence and the striking facial features. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature (in some patients) HEAD & NECK Head \- Microcephaly (head circumference 3 to 11 S.D. below mean) NEUROLOGIC Central Nervous System \- Mental retardation, mild to severe \- Decreased brain weight \- Disproportionately small cerebral cortex \- Seizures (rare) LABORATORY ABNORMALITIES \- Premature chromosome condensation MOLECULAR BASIS \- Caused by mutation in the microcephalin gene (MCPH1, 607117.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	MICROCEPHALY 1, PRIMARY, AUTOSOMAL RECESSIVE	c3711387	28,576	omim	https://www.omim.org/entry/251200	2019-09-22T16:25:13	{"doid": ["0070285"], "mesh": ["C579935"], "omim": ["251200"], "orphanet": ["2512"], "synonyms": ["Alternative titles", "PREMATURE CHROMOSOME CONDENSATION WITH MICROCEPHALY AND MENTAL RETARDATION", "PREMATURE CHROMOSOME CONDENSATION SYNDROME", "PCC SYNDROME"]}
For a general phenotypic description and a discussion of genetic heterogeneity of glioma, see GLM1 (137800). Mapping Pannu et al. (2002) studied genetic linkage in 15 familial glioma pedigrees ascertained through patients operated on at Tampere University Hospital and drawn from an area of 1 million inhabitants in western Finland. They hypothesized that the patients might carry the same low penetrance susceptibility allele. Pannu et al. (2002) used a 2-stage strategy for gene mapping. A genome screen in 4 families revealed 4 areas of interest; additional markers in these regions provided evidence of significant linkage to chromosome 15q23-q26.3 with a maximum nonparametric linkage score of 3.35 with marker D15S130. Investigation of all 15 glioma families by association analysis (haplotype pattern mining) and through use of the transmission-disequilibrium test gave further evidence of significant association/transmission distortion at the same 15q locus. No evidence of involvement of known tumor syndromes was obtained from the data provided by the linkage analysis or hospital records. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	GLIOMA SUSCEPTIBILITY 4	c0017638	28,577	omim	https://www.omim.org/entry/607248	2019-09-22T16:09:30	{"mesh": ["D005910"], "omim": ["607248"], "orphanet": ["182067"]}
A number sign (#) is used with this entry because of evidence that autosomal recessive congenital ichthyosis-1 (ARCI1) is caused by homozygous or compound heterozygous mutation in the gene encoding keratinocyte transglutaminase (TGM1; 190195) on chromosome 14q12. Description Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of disorders of keratinization characterized primarily by abnormal skin scaling over the whole body. These disorders are limited to skin, with approximately two-thirds of patients presenting severe symptoms. The main skin phenotypes are lamellar ichthyosis (LI) and nonbullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur (summary by Fischer, 2009). Neither histopathologic findings nor ultrastructural features clearly distinguish between NCIE and LI. In addition, mutations in several genes have been shown to cause both lamellar and nonbullous ichthyosiform erythrodermal phenotypes (Akiyama et al., 2003). At the First Ichthyosis Consensus Conference in Soreze in 2009, the term 'autosomal recessive congenital ichthyosis' (ARCI) was designated to encompass LI, NCIE, and harlequin ichthyosis (ARCI4B; 242500) (Oji et al., 2010). NCIE is characterized by prominent erythroderma and fine white, superficial, semiadherent scales. Most patients present with collodion membrane at birth and have palmoplantar keratoderma, often with painful fissures, digital contractures, and loss of pulp volume. In half of the cases, a nail dystrophy including ridging, subungual hyperkeratosis, or hypoplasia has been described. Ectropion, eclabium, scalp involvement, and loss of eyebrows and lashes seem to be more frequent in NCIE than in lamellar ichthyosis (summary by Fischer et al., 2000). In LI, the scales are large, adherent, dark, and pigmented with no skin erythema. Overlapping phenotypes may depend on the age of the patient and the region of the body. The terminal differentiation of the epidermis is perturbed in both forms, leading to a reduced barrier function and defects of lipid composition in the stratum corneum (summary by Lefevre et al., 2006). In later life, the skin in ARCI may have scales that cover the entire body surface, including the flexural folds, and the scales are highly variable in size and color. Erythema may be very mild and almost invisible. Some affected persons exhibit scarring alopecia, and many have secondary anhidrosis (summary by Eckl et al., 2005). ### Genetic Heterogeneity of Autosomal Recessive Congenital Ichthyosis Autosomal recessive congenital ichthyosis-2 (ARCI2; 242100) is caused by mutation in the ALOX12B gene (603741) on chromosome 17p13. ARCI3 (606545) is caused by mutation in the ALOXE3 gene (607206) on chromosome 17p13. ARCI4A (601277) and ARCI4B (harlequin ichthyosis; 242500) are caused by mutation in the ABCA12 gene (607800) on chromosome 2q35. ARCI5 (604777) is caused by mutation in the CYP4F22 gene (611495) on chromosome 19p13. ARCI6 (612281) is caused by mutation in the NIPAL4 gene (ichthyin; 609383) on chromosome 5q33. ARCI7 (615022) has been mapped to chromosome 12p11. ARCI8 (613943) is caused by mutation in the LIPN gene (613924) on chromosome 10q23. ARCI9 (615023) is caused by mutation in the CERS3 gene (615276) on chromosome 15q26. ARCI10 (615024) is caused by mutation in the PNPLA1 gene (612121) on chromosome 6p21. ARCI11 (602400) is caused by mutation in the ST14 gene (606797) on chromosome 11q24. ARCI12 (617320) is caused by mutation in the CASP14 gene (605848) on chromosome 19p13. ARCI13 (617574) is caused by mutation in the SDR9C7 gene (609769) on chromosome 12q13. ARCI14 (617571) is caused by mutation in the SULT2B1 gene (604125) on chromosome 19q13. Ichthyosis prematurity syndrome (608649) is a self-improving form of ichthyosis that includes respiratory complications at birth and persistent eosinophilia and is caused by mutation in the FATP4 (SLC27A4; 604194) gene. A rare syndromic form of NCIE, Chanarin-Dorfman syndrome (275630), is caused by mutation in the ABHD5 gene (604780). Clinical Features The neonate with lamellar ichthyosis presents at birth with a collodion-like membrane encasing the neonate; the skin later develops large, brown, platelike scales covering the entire body (Williams and Elias, 1985). See picture in Sorsby (1953). Russell et al. (1994) reported patients with a severe LI phenotype (nonerythrodermic) from 13 families; 17 patients from 7 U.S. families and 10 patients from 6 Egyptian families. All patients had congenital onset of their skin disease. Of 22 patients in whom this information was available, 21 had a history of collodion presentation at birth. Nineteen of 27 patients had ectropion, and half had alopecia with scarring of the scalp. Tok et al. (1999) reported monozygotic African American twin girls who were born with collodion membrane, ectropion, and eclabium. The membranes were shed within 4 to 6 weeks, and the ectropion and eclabium also resolved spontaneously within 3 weeks without sequelae. At 2 months of age, both infants developed large thick brown scales covering nearly the entire integument, sparing only the face and flexural surfaces. The authors also described a male infant of Italian origin, born with collodion membrane, ectropion, and eclabium, who developed large thick scales throughout the entire integument including the face and flexural surfaces. The ectropion and eclabium resolved without sequelae. Both sets of parents were unaffected. Cruz et al. (2000) reviewed the eyelid abnormalities in 8 patients with lamellar ichthyosis and 2 patients with nonbullous congenital ichthyosiform erythroderma. All 8 patients presented with cicatricial lagophthalmos (inability to appose the eyelids due to cutaneous scarring). Of the 8 patients with classic LI, 5 had ectropion of all 4 eyelids, 1 had only lower ectropion, and 2 had no ectropion. The 2 patients with NCIE had distinct eyelid abnormalities, including madarosis (eyelash loss) and eyelash retraction. Three patients with classic LI had severe visual loss from corneal damage. Of these 3 patients, 2 did not have upper ectropion. The authors concluded that severe corneal damage and visual loss could occur in LI even in the absence of upper or lower ectropion. Lugassy et al. (2008) studied a female infant with ARCI from a consanguineous Iranian family, in whom they identified homozygosity for a frameshift mutation in the TGM1 gene. The patient was born with collodion membrane and in the second month of life showed erythroderma and widespread scaling. No hair was visible on any part of the body, and she also had severe nail dystrophy and failure to thrive. ### Self-Healing Collodion Baby Collodion babies look very much alike at birth, but later take different clinical courses. Most patients evolve into the different types of congenital ichthyosis, but about 10% heal spontaneously within the first few weeks (Raghunath et al., 2003). This benign and self-limited clinical course, termed 'self-healing collodion baby,' distinguishes this condition from TGM1-deficient lamellar ichthyosis. Mazereeuw-Hautier et al. (2009) reported a nonconsanguineous French family in which 2 sisters had different ichthyosis phenotypes: the older sister was born as a classic generalized collodion baby, and later developed the lamellar form of ichthyosis, with large dark scales all over her body. The younger sister presented at birth with a collodion baby phenotype in a localized acral distribution, with only the 2 distal phalanges of her fingers and toes embedded in glistening, tight skin leading to constricting bands and cracks. The dorsal surface of the hands appeared slightly edematous, but the rest of the skin was normal apart from mild scaling and erythema that appeared to be related to the newborn status. Her skin abnormalities healed within a few weeks and she had normal skin at 7 years of age. The parents reported no family history of similar skin changes in the newborn period. Histochemical transglutaminase-1 assay in skin biopsies from the 2 sisters showed that the younger sister with acral self-healing collodion baby had slightly reduced enzyme function compared to a control skin biopsy, whereas the older sister with LI had complete absence of enzyme activity. Vahlquist et al. (2010) studied 11 Swedish and 4 Danish patients with autosomal recessive congenital ichthyosis of the 'self-healing' type, all of whom were born with a variably thick collodion membrane, with ectropion present in 8 cases. The membrane was spontaneously shed after 2 to 4 weeks, exposing almost normal-appearing skin. Examination at 2 years to 37 years of age, however, revealed that all of the patients had varying degrees of mild ichthyosis, consisting of scaling in the armpits, acral hyperkeratosis and keratoderma, coarse scales on the scalp, and fine scaling around the neck, together with xerotic extremities and red cheeks that stung with exposure to salt water. All but 1 of the patients exhibited moderate to severe anhidrosis; the patient with normal sweating was an 18-year-old Swedish girl who was compound heterozygous for mutations in the TGM1 gene and whose residual skin symptoms, consisting of fine scaling and xerosis with palmoplantar fissures, improved in summer. Vahlquist et al. (2010) proposed the term 'self-improving collodion ichthyosis' (SICI) as a better designation for this phenotype. ### Bathing Suit Distribution of Ichthyosis Bathing suit ichthyosis (BSI) is a form of ARCI characterized by collodion membrane at birth, encasing the entire skin, with clinical healing of the ichthyosis on the arms and legs during the first weeks of life (Oji et al., 2006). Petit et al. (1997) described a 4-year-old girl with an unusual distribution of the lamellar form of ichthyosis, which involved large dark brown scales affecting the trunk, neck, and scalp but sparing the face and limbs. Yang et al. (2001) reported a Japanese girl and a Korean boy who had similar clinical histories: both were born with collodion membrane and developed ectropion and eclabium at 1 day of age. At 1 month of age, the ectropion and eclabium had improved, and the dry collodion membrane peeled off to reveal large, slightly brownish scales primarily on the trunk, with near-normal appearance of other body sites, although the skin was dry. At 6 months of age, the girl's scales became fine and white, and were successfully controlled with petroleum. By 1 year of age, the brownish scales in the boy were confined to his forehead, buttocks, and flanks. Akiyama et al. (2001) described a 56-year-old Japanese woman, born of nonconsanguineous parents, who had a mild form of lamellar ichthyosis involving thick dark gray lamellar scales covering her neck, abdomen, center of the back, and bilateral axillae. She was not born with collodion, and thick scales had appeared during infancy. The skin on her face and extremities appeared normal, and she did not display hyperkeratosis of the palms or soles. The severity of scaling was stable without the use of retinoids or topical steroids, although the scaling worsened and affected areas enlarged during the summer. Family history revealed that an older sister with ichthyosis had died at 1 week of age of unknown cause. Light microscopy of lesional skin showed marked hyperkeratosis with only a small number of parakeratotic cells, and electron microscopy demonstrated thickening of the cornified cell envelope during keratinization of the epidermis. Jacyk (2005) reported 13 South African black patients from 12 families who displayed the lamellar form of autosomal recessive ichthyosis in a distribution involving the trunk, the most proximal parts of the upper limbs including the axillae, scalp, and neck, but sparing the central face and extremities. The scales were dark brown, large, and plate-like. Palms and soles were dry, with diffuse, mild hyperkeratosis; the dorsal surfaces appeared normal and there were no nail changes. Skin lesions were present at birth in all, and in 10 patients the presentation was compatible with collodion baby. Consanguinity was denied but both parents of 10 patients belonged to the same ethnic group and came from the same rural area, often from the same village. Light microscopy of biopsies from the lower back showed marked hyperkeratosis, no parakeratosis, granular layer of 1 to 3 layers of cells, mild to moderate acanthosis, and mild lymphocytic infiltrate in the upper dermis. Electron microscopy did not reveal cholesterol clefts or lipid droplets in the thickened corneal layer. Jacyk (2005) proposed the term 'bathing suit ichthyosis' for this condition. Oji et al. (2006) described 10 probands from Germany, France, Turkey, the Netherlands, or Morocco who fulfilled the clinical criteria for BSI. All patients were born with collodion membrane, and during the first to second month of life, they developed a lamellar scaling on the trunk, whereas the 4 limbs and face were almost completely spared. The severity of scaling varied widely, with some patients having large, thick, dark scales with involvement of very specific areas on the extremities and the face, others having mild brownish scaling that was most pronounced in the axillae and on the neck, and a few having moderate scaling of affected areas. A 16-year-old proband from Germany and his affected brother had a variable course, presenting with a bathing suit distribution in infancy but developing a tendency towards more generalized and rather mild ichthyosis. Five patients displayed fine linear scaling on the inner forearm and very pronounced scaling in the axillae, on the neck, and on medial parts of the trunk, sparing the suprarenal lumbar areas. Digital thermography in healthy individuals showed a striking correlation between warmer body sites and the 'bathing suit' distribution of scaling, leading Oji et al. (2006) to conclude that temperatures above approximately 33 degrees Celsius predispose to the development of ichthyosis in these patients. ### Ultrastructural Features of Autosomal Recessive Congenital Ichthyosis Patients with autosomal recessive congenital ichthyosis have structural changes affecting terminal differentiation and keratinization within the epidermis, which can be seen using electron microscopy (EM). Dahlqvist et al. (2007) stated that about half of patients with ARCI investigated by EM lack unique characteristics of the epidermis, but the remaining patients show defined ultrastructural markers that can be categorized into 4 main patterns: type I is characterized by broad stratum granulosum and numerous lipid vacuoles in corneocytes; type II shows clefts of former cholesterol crystals in stratum corneum; type III is characterized by abnormal lamellar bodies in stratum granulosum and perinuclear, elongated membranes; and type IV shows lipid membrane aggregations in upper epidermal cells. All individuals but 1 studied by Dahlqvist et al. (2007) in whom NIPAL4 (609383) mutations were found (ARCI6; 612281) fulfilled the EM criteria of ARCI EM type III. Laiho et al. (1999) restudied 38 Finnish families with autosomal recessive congenital ichthyosis, in 13 (34%) of which TGM1 mutations had been found (Laiho et al., 1997), and compared the molecular genetic alterations with clinical and electron microscopic findings of these patients. On the basis of electron microscopy in ichthyosis congenita, the families were classified as types I, II, III, IV, and an undefined group. TGM1 gene mutations were found in all of the autosomal recessive congenital ichthyosis cases of type II and in one-third of type I families. The typical clinical phenotype of the TGM1 mutation carrier included large, thick, brownish scales, but ichthyosis of some of the patients tended to be milder. Type II is the most clearly defined of the congenital ichthyosis groups. Patients have a clear clinical picture of classic lamellar ichthyosis with large brown scales. Crystalloid structures (cholesterol clefts) in the thickened corneal layer are used as an electron-microscopic marker for ichthyosis congenita type II and were found in every patient. The ultrastructural markers in type III patients were elongated membrane structures, abnormal keratinosomes, and vesicular complexes in upper epidermal and horny cells. The clinical picture differed from that in other types: the onset of ichthyosis was variable, ichthyosis as well as erythema could be patchy or generalized, and flexures were typically involved. Pathogenesis In the stratum corneum of patients with lamellar ichthyosis, the amount of free fatty acids is decreased, the ceramide profile is altered, and there are elevated levels of transepidermal water loss indicative of an impaired barrier function. As ceramides and free fatty acids are essential for a proper barrier function, Pilgram et al. (2001) hypothesized that changes in the composition of these lipids would be reflected in the lipid organization in stratum corneum of patients with lamellar ichthyosis. They investigated lateral lipid packing using electron diffraction and lamellar organization using freeze-fracture electron microscopy. In LI stratum corneum, hexagonal packing was predominant, whereas orthorhombic packing was observed only occasionally. The finding that the lateral lipid organization in LI skin is predominantly hexagonal was in good agreement with stratum corneum lipid model studies showing that long-chain free fatty acids are required to form an orthorhombic lattice. The results in this study also confirmed the hypothesis that an orthorhombic packing is required for proper stratum corneum barrier function. Aufenvenne et al. (2009) studied 8 of the TGM1 mutations that were identified by Oji et al. (2006) in patients who had ichthyosis in a bathing suit distribution (BSI; see, e.g., 190195.0029-190195.0032) as well as 3 mutations associated with classic LI (see, e.g., 190195.0007). Using fluorescence spectrometry to analyze enzyme activity, Aufenvenne et al. (2009) demonstrated that both the BSI- and LI-associated mutations had decreased enzyme activity compared to wildtype, but the BSI mutations exhibited a marked shift in temperature optimum from 37 degrees Celsius to 31 degrees Celsius, with residual activity ranging between 13% and 16.5% at the lower temperature, whereas activity at 37 degrees Celsius was less than 7.5%. Deficient activity of the BSI mutations could be reconstituted by decreasing the temperature to below 33 degrees Celsius. Aufenvenne et al. (2009) concluded that the striking distribution of scaling in BSI is due to mutations that render TGase-1 sensitive to temperatures above 33 degrees Celsius. Clinical Management Aufenvenne et al. (2013) developed liposomal preparations with encapsulated recombinant human TGM1 and tested them in a skin-humanized mouse model. In situ monitoring revealed a restoration of TGM1 activity, and cholesterol clefts vanished ultrastructurally. Immunohistochemical staining of TGM1 substrates showed a normalization of the distribution patterns. Measurement of transepidermal water loss showed that normal epidermal barrier function was restored. Aufenvenne et al. (2013) concluded that this topical approach might be a promising strategy towards a causal cure for individuals with chronic and disfiguring TGM1 deficiency, who often must spend 2 to 3 hours a day in treatment for their skin. Inheritance Wile (1924) reported 3 affected males, the offspring of matings in which 2 brothers married 2 sisters, who were their first cousins. Arce and Berchmans (1969) described ichthyosiform dermatosis in 13 members of an inbred Brazilian kindred. Nix et al. (1963) described 9 cases among 22 offspring of 3 couples of German extraction. All 6 parents had a common ancestral couple. Rossmann-Ringdahl et al. (1986) described NCIE in a woman and both of her children. Although her husband was not known to be related, this was thought to be pseudodominant inheritance. Williams and Elias (1986), however, thought that this might represent a true dominant form of 'lamellar' ichthyosis (146750). They pointed to the kindred reported by Traupe et al. (1984) with affected persons in 3 generations and mentioned a similar family of their own. Population Genetics Russell et al. (1994) cited a prevalence of lamellar ichthyosis of approximately 1 in 200,000 persons. Lefevre et al. (2006) stated that the estimated incidence of ARCI is between 1 in 300,000 and 1 in 500,000. Mapping Studying families with LI in the United States and in Egypt, Russell et al. (1994) tested for linkage with markers in the region of genes that are candidates for the site of the mutation by reason of being involved in formation of the stratum corneum. Analysis in both inbred and outbred families showed that severe LI was linked to several markers within a 9.3-cM region on chromosome 14q11. Affected individuals in inbred families were found to have striking homozygosity for markers in this region. Linkage-based genetic counseling and prenatal diagnosis is now available for informative at-risk families. The transglutaminase-1 gene maps to the same region and encodes one of the enzymes responsible for crosslinking epidermal proteins during formation of the stratum corneum. Russell et al. (1994) showed that TGM1 and LI were linked with no recombinants; maximum lod = 9.11. Arita et al. (2007) performed SNP genotyping on DNA samples from 8 South African black patients with autosomal recessive congenital ichthyosis in a bathing suit distribution, 5 of whom had been previously reported by Jacyk (2005). From the SNP assay analysis, 7 regions of the genome were found to have large blocks of homozygosity for all affected individuals, including a 1.2-Mb interval on chromosome 14q11 that contains the TGM1 gene. Molecular Genetics Huber et al. (1995) observed that affected individuals in 3 families with autosomal recessive lamellar ichthyosis exhibited drastically reduced transglutaminase activity; in 2 of the families, expression of TGM1 transcripts was diminished or abnormal and no TGM1 protein was detected. Analysis of the TGM1 gene revealed homozygous or compound heterozygous mutations of the TGM1 gene in all 3 families (see 190195.0001-190195.0005). The results suggested that intact cross-linkage of cornified cell envelopes is required for epidermal tissue homeostasis. In 2 multiplex families with severe autosomal recessive lamellar ichthyosis that had been linked to 14q11 and TGM1 by Russell et al. (1994), Russell et al. (1995) identified compound heterozygosity for missense mutations in the TGM1 gene (190195.0006 and 190195.0007). Laiho et al. (1997) analyzed the TGM1 gene in 49 patients from 38 Finnish families with autosomal recessive congenital ichthyosis and identified homozygosity or compound heterozygosity for 5 different mutations in affected individuals from 13 families (see 190195.0004, 190195.0006, 190195.0008, 190195.0009, and 190195.0023). In 2 patients the second mutation was unknown. Some patients had the lamellar form of ichthyosis whereas others exhibited nonbullous congenital ichthyosiform erythroderma. Haplotype analysis revealed that the most common mutation, R142C (190195.0004), had been introduced twice into the Finnish population. In a 4-year-old girl with an unusual distribution of the lamellar form of ichthyosis, which involved large dark brown scales affecting the trunk, neck, and scalp but sparing the face and limbs, Petit et al. (1997) identified homozygosity for a missense mutation in the TGM1 gene (V382M; 190195.0010). Functional analysis of cultured keratinocytes demonstrated a profound reduction of membrane-bound as well as cytosolic transglutaminase (TG) activity in both affected and unaffected skin from the patient compared to controls. Immunoblot analysis of cytoplasmic and membrane keratinocyte extracts revealed no detectable TGK protein in affected or unaffected skin from the patient, although Northern blot analysis showed TGM1 mRNA of normal size and comparable amounts with an age-matched control. Petit et al. (1997) proposed that other mechanisms may compensate for TGK deficiency in unaffected skin, and suggested that the regulation of the formation of the cornified envelope might differ between these different areas of skin. Pigg et al. (1998) studied 36 Norwegian families with lamellar ichthyosis and 7 with nonbullous congenital ichthyosiform erythroderma using microsatellite markers linked to the TGM1 gene, and found a common haplotype for 2 markers on 74% of disease-associated chromosomes. In 3 individuals homozygous for the common haplotype, 2 with lamellar ichthyosis and 1 with congenital ichthyosiform erythroderma, homozygosity for a splice site mutation in the TGM1 gene was identified (IVS5-2A-G; 190195.0002). Screening of probands from the remaining 40 families revealed the splice site mutation on 61 of 72 alleles associated with lamellar ichthyosis and on 9 of 15 alleles associated with congenital ichthyosiform erythroderma. These findings suggested a single founder mutation for most patients with ARCI in Norway. In African American twin girls with lamellar ichthyosis that spared the face and flexural surfaces, Tok et al. (1999) identified homozygosity for a missense mutation in the TGM1 gene (R315L; 109195.0033). In a male infant of Italian extraction who had lamellar ichthyosis over his entire integument, they identified compound heterozygosity for mutations in TGM1. Shevchenko et al. (2000) studied 5 American families with the IVS5-2A-G mutation in the TGM1 gene, noting that all had the lamellar form of ichthyosis and that patients who were homozygous for the splice site mutation were less severely affected than many of the compound heterozygotes. None were of Norwegian ancestry, and genealogic information provided evidence that the founder chromosome may have arisen in the Westphalia region of Germany, with introduction into the Norwegian population around 1000 to 1100 A.D. In a Japanese boy with ARCI who displayed nonbullous congenital ichthyosiform erythroderma consisting of fine gray or light brown scales on an erythematous skin, Akiyama et al. (2001) identified compound heterozygosity for a missense mutation and a 1-bp deletion in the TGM1 gene (190195.0011 and 190195.0012, respectively). Cserhalmi-Friedman et al. (2001) analyzed the TGM1 gene in 10 ARCI patients with the lamellar form of ichthyosis and identified compound heterozygosity for 14 different mutations in 7 patients (see, e.g., 190195.0014-190195.0020 and 190195.0024-190195.0026). Erythema in the 10 patients varied from mild to moderate, and 2 of them had small scales. Cserhalmi-Friedman et al. (2001) stated that the clinical presentation of patients with and without mutations was virtually indistinguishable. In a Japanese girl and a Korean boy with similar clinical histories, who both had ichthyosis in a distribution affecting primarily the trunk, Yang et al. (2001) identified compound heterozygosity for missense mutations in the TGM1 gene, N228T (190195.0021), R306W (190195.0022), and D101V (190195.0027). In a 56-year-old Japanese woman with a mild form of lamellar ichthyosis limited to the neck, abdomen, center of the back, and bilateral axillae, Akiyama et al. (2001) identified compound heterozygosity for 2 missense mutations in the TGM1 gene, R306W and L204Q (190195.0028). Raghunath et al. (2003) described 2 sibs with ARCI who presented the self-healing collodion baby phenotype; they had markedly diminished TGM1 epidermal activity and were found to be compound heterozygous for missense mutations in the TGM1 gene (190195.0013 and 190195.0014). Molecular modeling and biochemical assays of mutant proteins under elevated hydrostatic pressure suggested significantly reduced activity in G278R and a chelation of water molecules in D490G that locked the mutated enzyme in an inactive trans conformation in utero. After birth, these water molecules were removed and the enzyme was predicted to isomerize back to a partially active cis form, explaining the dramatic improvement of this skin condition. Oji et al. (2006) sequenced the TGM1 gene in 10 ARCI probands from Germany, France, Turkey, the Netherlands, or Morocco, who fulfilled the clinical criteria for 'bathing suit' ichthyosis (BSI), and identified homozygosity or compound heterozygosity for TGM1 mutations in all patients (see, e.g., 190195.0002, 190195.0007, 190195.0029-190195.0032). Digital thermography in healthy individuals showed a striking correlation between warmer body sites and the 'bathing suit' distribution of scaling, and in situ TGase testing in the skin of BSI patients demonstrated a marked decrease of enzyme activity when the temperature was increased from 25 to 37 degrees Celsius. Oji et al. (2006) concluded that the bathing suit form of ichthyosis is caused by TGM1 deficiency and that it is a temperature-sensitive phenotype. In 8 South African black patients with autosomal recessive congenital ichthyosis in a bathing suit distribution mapping to chromosome 14q11, 5 of whom had previously been reported by Jacyk (2005), Arita et al. (2007) sequenced the candidate gene TGM1 and identified homozygosity for a missense mutation (R315L; 190195.0033). Arita et al. (2007) noted that the R315L mutation had previously been identified by Tok et al. (1999) in African American twins who had a more classic presentation of lamellar ichthyosis in which skin scaling was extensive, sparing only the face and the flexures. In a French family in which 1 sister had a lamellar ichthyosis phenotype and another sister presented a self-healing collodion baby phenotype limited to an acral distribution, Mazereeuw-Hautier et al. (2009) identified 3 mutations in the TGM1 gene: the sister with the self-healing collodion baby phenotype was compound heterozygous for 2 missense mutations in TGM1, V359M (190195.0034) and R396H (190195.0035), whereas the sister with classic LI was compound heterozygous for R396H and a 7-bp deletion (190195.0036). Their unaffected mother was heterozygous for the R396H mutation, and their apparently unaffected father was a compound heterozygote for V359M and the 7-bp deletion; none of the mutations was found in 100 unrelated Caucasian controls. Mazereeuw-Hautier et al. (2009) noted that a transient and mild anomaly of the skin at birth could not be ruled out in the father. In a female infant with ARCI from a consanguineous Iranian family, Lugassy et al. (2008) identified homozygosity for a 1-bp deletion in the TGM1 gene that segregated with disease in the family and was not found in 50 controls. The patient was born with collodion membrane and in the second month of life showed erythroderma and widespread scaling. No hair was visible on any part of the body, and she also had severe nail dystrophy. In 16 Spanish ARCI families from Galicia, Rodriguez-Pazos et al. (2011) analyzed 5 ARCI-associated genes and identified TGM1 mutations in 11 probands, who all exhibited the lamellar form of ichthyosis. Three mutations accounted for 41%, 23%, and 14% of the TGM1 mutant alleles, respectively (see, e.g., 190195.0038 and 190195.0039). In 4 probands, no causative variants were identified; and 1 proband, who a congenital ichthyosiform erythroderma phenotype, was compound heterozygous for missense mutations in the ALOXE3 gene. Rodriguez-Pazos et al. (2011) concluded that the high percentage of patients with the same TGM1 mutation, together with the high number of homozygous probands (64%), indicated the existence of a strong founder effect in this population, with an estimated prevalence of 1:122,000 for Galicia. ### Genetic Heterogeneity Huber et al. (1995) demonstrated apparent genetic heterogeneity of lamellar ichthyosis; they described 2 sporadic cases with normal transglutaminase activity and by Western and Northern blot analyses normal size and quantities of keratinocyte transglutaminase protein and mRNA. Sequencing of the 15 exons and their flanking regions demonstrated no deviation from the published sequence. Consanguinity was suspected in one case but not in the second. By linkage analysis, haplotype analysis, and direct sequencing, respectively, Petit et al. (1997) excluded the TGM1 gene as the cause of ARCI in 4 patients from 3 families. Two of the patients were sisters who exhibited a classic lamellar form of ichthyosis, whereas the other 2 patients had moderate lamellar ichthyosis with finer scaling and variable erythema. Eckl et al. (2009) studied 250 unrelated patients representing the entire phenotypic spectrum of ARCI, including 15 patients from families previously studied by Eckl et al. (2005), and found that mutations in TGM1 accounted for 38% of the cases, whereas mutations in the ALOX12B (603741) and ALOXE3 (607206) genes each represented 6.8% of the cases. Fischer (2009) stated that in a cohort of 520 independent ARCI families, mutations were identified in 78% of patients by direct sequencing of 6 genes associated with ARCI: 32% of patients were found to have mutations in TGM1, 12% in ALOX12B, and 5% in ALOXE3, accounting for 49% of the total; 29% of the mutations were found in the remaining 3 genes: 16% in ichthyin (NIPAL4; 609383), 8% in CYP4F22 (611495), and 5% in ABCA12 (607800). In 15 Scandinavian patients with ARCI of the self-healing collodion baby type, Vahlquist et al. (2010) analyzed 7 ARCI-related genes and identified homozygosity or compound heterozygosity for mutations in the ALOX12B gene in 8 patients (see, e.g., 603741.0012 and 603741.0013), in the ALOXE3 gene in 3 patients (see, e.g., 607206.0008), and in the TGM1 gene in 1 patient. No mutations were identified in the 3 remaining patients, suggesting that mutations in additional, as yet unidentified genes may also lead to a self-improving collodion ichthyosis phenotype. Genotype/Phenotype Correlations Hennies et al. (1998) investigated the genotype/phenotype correlation in 14 families with lamellar ichthyosis. Linkage analyses using microsatellites in the region of the TGM1 gene confirmed genetic heterogeneity. In patients not linked to the TGM1 gene, the second region identified on chromosome 2 and a further candidate region on chromosome 20 were excluded, confirming as well the existence of at least 3 loci for lamellar ichthyosis. Sequence analyses of the TGM1 gene in families compatible with linkage of lamellar ichthyosis to that locus revealed 7 different missense mutations, 5 of which had not previously been reported, and 1 splice mutation. No genotype/phenotype correlation for the mutations in the TGM1 gene could be found in this group of patients, which included 2 unrelated patients homozygous for the same mutation. Similarly, no clear difference in the same clinical picture was seen between patients with the TGM1 mutations and those unlinked to the TGM1 locus. Comparison of genetic and clinical classifications of patients with lamellar ichthyosis showed no consistency and thus indicated that clinical criteria used at that time could not discriminate between the molecularly different forms of the disease. Farasat et al. (2009) identified TGM1 mutations in 57 (55%) of 104 patients with autosomal recessive congenital ichthyosis, including 22 novel mutations. The presence of a TGM1 mutation was significantly associated with collodion membrane at birth, ectropion, plate-like scales, and alopecia. Patients with at least 1 truncating mutation were more likely to have severe hypohidrosis and overheating at onset of symptoms compared to those with missense mutations. There was a high frequency of mutated arginine codons, most likely due to the deamination of CpG dinucleotides. The most common mutation was an A-to-G transition in intron 5 (190195.0002), which accounted for 28% of the mutated alleles. Hackett et al. (2010) reported TGM1 mutations in 5 patients with ARCI who were born with collodion membrane, 3 of whom went on to develop the characteristic bathing suit distribution of ichthyosis (BSI; see, e.g., 190195.0033) and 2 of whom developed a self-healing collodion baby phenotype. The authors also reviewed the phenotypes associated with the more than 40 reported mutations in TGM1 and noted that BSI and SHCB mutations appeared to cluster in exons 5, 6, and 7 of the TGM1 gene. Nomenclature Vahlquist (2010) proposed a subclassification of ARCI for the self-improving forms of ichthyosis, including self-healing collodion baby and ichthyosis prematurity syndrome (IPS), to be designated 'pleomorphic ichthyosis' (PI). Traupe (2010) argued that 'pleomorphic' was not an ideal term since in most cases the ichthyosis simply improves, and suggested 'congenital ichthyosis with mild scaling' (CIMS). In addition, Traupe (2010) noted that the concept of an umbrella term to describe mild ARCI cases was not universally accepted at the Soreze consensus conference on ichthyosis (Oji et al., 2010) and did not enter the new classification scheme. Taieb and Morice-Picard (2010) stated that the IPS subtype would be better termed 'self-healing congenital verruciform hyperkeratosis.' History MacKee and Rosen (1917) reviewed the subject of congenital ichthyosiform erythroderma. Rand and Baden (1983) considered recessive lamellar ichthyosis to be synonymous with congenital nonbullous ichthyosiform erythroderma, whereas Wells and Kerr (1965) considered them separate entities. Williams (1983) noted that there may be biochemical differences. The experience of Holbrook et al. (1988) suggested that diagnosis on the basis of the morphology of fetal skin biopsies is fraught with uncertainty. INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Taut facial skin Eyes \- Ectropion Mouth \- Eclabium SKELETAL Limbs \- Joint contractures (in some patients) Hands \- Digital necrosis (in some patients) Feet \- Digital necrosis (in some patients) SKIN, NAILS, & HAIR Skin \- Collodion membrane at birth (in most patients) \- Self-healing collodion baby (in some patients) \- Large dark plate-like scales \- Fine white scales \- Erythroderma \- Bathing suit distribution of ichthyosis (in some patients) \- Hypohidrosis or anhidrosis (in some patients) \- Palmoplantar hyperkeratosis, mild (in some patients) Skin Histology \- Marked hyperkeratosis \- Parakeratosis, minimal to none \- Acanthosis, mild to moderate \- Lymphocytic infiltrate in upper dermis, mild Electron Microscopy \- Thickening of cornified cell envelope during keratinization \- Cholesterol clefts in thickened stratum corneum \- Broad stratum granulosum \- Lipid vacuoles in corneocytes Nails \- Dystrophic nails (in some patients) Hair \- Alopecia (in some patients) \- Hypotrichosis (in some patients) MISCELLANEOUS \- Seasonal variation in severity of skin symptoms reported by some patients MOLECULAR BASIS \- Caused by mutation in the transglutaminase 1 gene (TGM1, 190195.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	ICHTHYOSIS, CONGENITAL, AUTOSOMAL RECESSIVE 1	c1855789	28,578	omim	https://www.omim.org/entry/242300	2019-09-22T16:26:28	{"doid": ["0060656"], "mesh": ["C565473", "D017490"], "omim": ["242300"], "icd-10": ["Q80.2"], "orphanet": ["313", "281122", "100976"], "synonyms": ["ICHTHYOSIS CONGENITA II", "COLLODION BABY, SELF-HEALING", "LAMELLAR EXFOLIATION OF NEWBORN", "DESQUAMATION OF NEWBORN", "LI", "ICHTHYOSIS, CONGENITAL, AUTOSOMAL RECESSIVE 1, WITH BATHING SUIT DISTRIBUTION", "Congenital lamellar ichthyosis", "Alternative titles", "ICHTHYOSIS, LAMELLAR, 1, FORMERLY", "ICHTHYOSIS CONGENITA", "Classic lamellar ichthyosis", "COLLODION FETUS"], "genereviews": ["NBK1420"]}
A rare autosomal recessive acromesomelic dysplasia characterized by severe dwarfism (adult height >120 cm), both axial and appendicular involvement (shortening of the middle and distal segments of limbs and vertebral shortening), and with normal facial appearance and intelligence. It is a less severe form than acromesomelic dysplasia, Grebe type and acromesomelic dysplasia, Hunter-Thomson type . [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Acromesomelic dysplasia, Maroteaux type	c1864356	28,579	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=40	2021-01-23T18:43:06	{"gard": ["507"], "mesh": ["C535661"], "omim": ["602875"], "umls": ["C1864356"], "icd-10": ["Q77.8"]}
A bony bridge (ponticulus posterius) on the first cervical vertebra, roofing the groove occupied by the vertebral artery, behaves as a dominant trait. The gene has a frequency of about 0.15. Spine \- Bony bridge on first cervical vertebra Radiology \- Roofed first cervical vertebral groove occupied by the vertebral artery Inheritance \- Autosomal Dominant ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	CERVICAL VERTEBRAL BRIDGE	c1861694	28,580	omim	https://www.omim.org/entry/118000	2019-09-22T16:43:24	{"omim": ["118000"]}
Peripheral giant-cell granuloma SpecialtyDentistry, ENT surgery Peripheral giant-cell granuloma (PGCG) is an oral pathologic condition that appears in the mouth as an overgrowth of tissue due to irritation or trauma. Because of its overwhelming incidence on the gingiva, the condition is associated with two other diseases, pyogenic granuloma and peripheral ossifying fibroma. These three diseases are associated because they appear frequently on gingiva. Due to its similar microscopic appearance, peripheral giant-cell granuloma is considered to be the soft tissue equivalent of central giant-cell granuloma. The appearance of peripheral giant-cell granuloma is also similar to pyogenic granuloma. The color ranges from red to bluish-purple, but is usually more blue in comparison to pyogenic granuloma. It can be sessile or pedunculated with the size usually being less than 2 cm. The lesion has a 60% gender predilection to females. The prevalence of the peripheral giant-cell granuloma is highest around 50 - 60 years of age. It appears only on the gingiva or on an edentulous alveolar ridge. It is more often found in the mandible rather than the maxilla, in either anterior or posterior areas. The underlying alveolar bone can be destroyed, leaving a unique appearance referred to as "cupping resorption" or "saucerization". ## Contents * 1 Diagnosis * 2 Treatment * 3 See also * 4 References * 5 External links ## Diagnosis[edit] Peripheral giant-cell granuloma appears microscopically as a large number of multinucleated giant cells, which can have up to dozens of nuclei. Additionally, there are mesenchymal cells that are ovoid and spindle-shaped. Near the borders of the lesion, deposits of hemosiderin and hemorrhage is often found. In 50% of cases, ulcerations are present. ## Treatment[edit] Treatment usually involves surgical removal of the lesion down to the bone. If there are any adjacent teeth, they are cleaned thoroughly by scaling and root planing (SRP) to remove any possible source of irritation. Recurrence is around 10%. ## See also[edit] * Central giant-cell granuloma ## References[edit] * Kahn, Michael A. Basic Oral and Maxillofacial Pathology. Volume 1. 2001. ## External links[edit] Classification D * ICD-10: K06.8 * ICD-9-CM: 523.8 * MeSH: D006101 * DiseasesDB: 30735 * v * t * e Oral and maxillofacial pathology Lips * Cheilitis * Actinic * Angular * Plasma cell * Cleft lip * Congenital lip pit * Eclabium * Herpes labialis * Macrocheilia * Microcheilia * Nasolabial cyst * Sun poisoning * Trumpeter's wart Tongue * Ankyloglossia * Black hairy tongue * Caviar tongue * Crenated tongue * Cunnilingus tongue * Fissured tongue * Foliate papillitis * Glossitis * Geographic tongue * Median rhomboid glossitis * Transient lingual papillitis * Glossoptosis * Hypoglossia * Lingual thyroid * Macroglossia * Microglossia * Rhabdomyoma Palate * Bednar's aphthae * Cleft palate * High-arched palate * Palatal cysts of the newborn * Inflammatory papillary hyperplasia * Stomatitis nicotina * Torus palatinus Oral mucosa – Lining of mouth * Amalgam tattoo * Angina bullosa haemorrhagica * Behçet's disease * Bohn's nodules * Burning mouth syndrome * Candidiasis * Condyloma acuminatum * Darier's disease * Epulis fissuratum * Erythema multiforme * Erythroplakia * Fibroma * Giant-cell * Focal epithelial hyperplasia * Fordyce spots * Hairy leukoplakia * Hand, foot and mouth disease * Hereditary benign intraepithelial dyskeratosis * Herpangina * Herpes zoster * Intraoral dental sinus * Leukoedema * Leukoplakia * Lichen planus * Linea alba * Lupus erythematosus * Melanocytic nevus * Melanocytic oral lesion * Molluscum contagiosum * Morsicatio buccarum * Oral cancer * Benign: Squamous cell papilloma * Keratoacanthoma * Malignant: Adenosquamous carcinoma * Basaloid squamous carcinoma * Mucosal melanoma * Spindle cell carcinoma * Squamous cell carcinoma * Verrucous carcinoma * Oral florid papillomatosis * Oral melanosis * Smoker's melanosis * Pemphigoid * Benign mucous membrane * Pemphigus * Plasmoacanthoma * Stomatitis * Aphthous * Denture-related * Herpetic * Smokeless tobacco keratosis * Submucous fibrosis * Ulceration * Riga–Fede disease * Verruca vulgaris * Verruciform xanthoma * White sponge nevus Teeth (pulp, dentin, enamel) * Amelogenesis imperfecta * Ankylosis * Anodontia * Caries * Early childhood caries * Concrescence * Failure of eruption of teeth * Dens evaginatus * Talon cusp * Dentin dysplasia * Dentin hypersensitivity * Dentinogenesis imperfecta * Dilaceration * Discoloration * Ectopic enamel * Enamel hypocalcification * Enamel hypoplasia * Turner's hypoplasia * Enamel pearl * Fluorosis * Fusion * Gemination * Hyperdontia * Hypodontia * Maxillary lateral incisor agenesis * Impaction * Wisdom tooth impaction * Macrodontia * Meth mouth * Microdontia * Odontogenic tumors * Keratocystic odontogenic tumour * Odontoma * Dens in dente * Open contact * Premature eruption * Neonatal teeth * Pulp calcification * Pulp stone * Pulp canal obliteration * Pulp necrosis * Pulp polyp * Pulpitis * Regional odontodysplasia * Resorption * Shovel-shaped incisors * Supernumerary root * Taurodontism * Trauma * Avulsion * Cracked tooth syndrome * Vertical root fracture * Occlusal * Tooth loss * Edentulism * Tooth wear * Abrasion * Abfraction * Acid erosion * Attrition Periodontium (gingiva, periodontal ligament, cementum, alveolus) – Gums and tooth-supporting structures * Cementicle * Cementoblastoma * Gigantiform * Cementoma * Eruption cyst * Epulis * Pyogenic granuloma * Congenital epulis * Gingival enlargement * Gingival cyst of the adult * Gingival cyst of the newborn * Gingivitis * Desquamative * Granulomatous * Plasma cell * Hereditary gingival fibromatosis * Hypercementosis * Hypocementosis * Linear gingival erythema * Necrotizing periodontal diseases * Acute necrotizing ulcerative gingivitis * Pericoronitis * Peri-implantitis * Periodontal abscess * Periodontal trauma * Periodontitis * Aggressive * As a manifestation of systemic disease * Chronic * Perio-endo lesion * Teething Periapical, mandibular and maxillary hard tissues – Bones of jaws * Agnathia * Alveolar osteitis * Buccal exostosis * Cherubism * Idiopathic osteosclerosis * Mandibular fracture * Microgenia * Micrognathia * Intraosseous cysts * Odontogenic: periapical * Dentigerous * Buccal bifurcation * Lateral periodontal * Globulomaxillary * Calcifying odontogenic * Glandular odontogenic * Non-odontogenic: Nasopalatine duct * Median mandibular * Median palatal * Traumatic bone * Osteoma * Osteomyelitis * Osteonecrosis * Bisphosphonate-associated * Neuralgia-inducing cavitational osteonecrosis * Osteoradionecrosis * Osteoporotic bone marrow defect * Paget's disease of bone * Periapical abscess * Phoenix abscess * Periapical periodontitis * Stafne defect * Torus mandibularis Temporomandibular joints, muscles of mastication and malocclusions – Jaw joints, chewing muscles and bite abnormalities * Bruxism * Condylar resorption * Mandibular dislocation * Malocclusion * Crossbite * Open bite * Overbite * Overeruption * Overjet * Prognathia * Retrognathia * Scissor bite * Maxillary hypoplasia * Temporomandibular joint dysfunction Salivary glands * Benign lymphoepithelial lesion * Ectopic salivary gland tissue * Frey's syndrome * HIV salivary gland disease * Necrotizing sialometaplasia * Mucocele * Ranula * Pneumoparotitis * Salivary duct stricture * Salivary gland aplasia * Salivary gland atresia * Salivary gland diverticulum * Salivary gland fistula * Salivary gland hyperplasia * Salivary gland hypoplasia * Salivary gland neoplasms * Benign: Basal cell adenoma * Canalicular adenoma * Ductal papilloma * Monomorphic adenoma * Myoepithelioma * Oncocytoma * Papillary cystadenoma lymphomatosum * Pleomorphic adenoma * Sebaceous adenoma * Malignant: Acinic cell carcinoma * Adenocarcinoma * Adenoid cystic carcinoma * Carcinoma ex pleomorphic adenoma * Lymphoma * Mucoepidermoid carcinoma * Sclerosing polycystic adenosis * Sialadenitis * Parotitis * Chronic sclerosing sialadenitis * Sialectasis * Sialocele * Sialodochitis * Sialosis * Sialolithiasis * Sjögren's syndrome Orofacial soft tissues – Soft tissues around the mouth * Actinomycosis * Angioedema * Basal cell carcinoma * Cutaneous sinus of dental origin * Cystic hygroma * Gnathophyma * Ludwig's angina * Macrostomia * Melkersson–Rosenthal syndrome * Microstomia * Noma * Oral Crohn's disease * Orofacial granulomatosis * Perioral dermatitis * Pyostomatitis vegetans Other * Eagle syndrome * Hemifacial hypertrophy * Facial hemiatrophy * Oral manifestations of systemic disease [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Peripheral giant-cell granuloma	None	28,581	wikipedia	https://en.wikipedia.org/wiki/Peripheral_giant-cell_granuloma	2021-01-18T18:34:05	{"icd-9": ["523.8"], "icd-10": ["K06.8"], "wikidata": ["Q7168704"]}
Permanent shortening of a muscle This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Muscle contracture" – news · newspapers · books · scholar · JSTOR (November 2008) (Learn how and when to remove this template message) Muscle contractures in terminal neurological condition Muscle contractures can occur for many reasons, such as paralysis, muscular atrophy, and forms of muscular dystrophy. Fundamentally, the muscle and its tendons shorten, resulting in reduced flexibility. For example, in the case of partial paralysis (i.e. poliomyelitis) the loss of strength and muscle control tend to be greater in some muscles than in others, leading to an imbalance between the various muscle groups around specific joints. Case in point: when the muscles which dorsiflex (flex the foot upward) are less functional than the muscles which plantarflex (flex the foot downward) a contracture occurs, giving the foot a progressively downward angle and loss of flexibility. Various interventions can slow, stop, or even reverse muscle contractures, ranging from physical therapy to surgery. A common cause for having the ankle lose its flexibility in this manner is from having sheets tucked in at the foot of the bed when sleeping. The weight of the sheets keep the feet plantarflexed all night. Correcting this by not tucking the sheets in at the foot of the bed, or by sleeping with the feet hanging off the bed when in the prone position, is part of correcting this imbalance. It occurs also due to muscle tightening for example if after fracture when immobilization is done by putting plaster of paris the muscle length shortens because the muscle is not used for a large span of time. ## Contents * 1 Cause * 1.1 Immobilization * 1.2 Spasticity * 1.3 Muscle weakness * 2 Treatment * 2.1 Passive stretching * 2.2 Splinting * 2.3 Electrical stimulation * 2.4 Surgery * 3 References ## Cause[edit] ### Immobilization[edit] Joints are usually immobilized in a shortened position resulting in changes within the joint connective tissue, and the length of the muscle and associated tendon. Prolonged immobilization facilitates tissue proliferation which impinges on the joint space.[1] Maintaining a shortened position for a prolonged period of time leads to: fibrous adhesion formation, loss of sarcomeres, and a loss of tissue extensibility.[1] ### Spasticity[edit] If spasticity is left untreated, contractures can occur. A loss of muscle tone inhibition causes a muscle to become hyperactive resulting in constant contraction, which reduces an individual’s control of the affected area. The joint will remain in a flexed state producing similar effects as listed in immobilization. ### Muscle weakness[edit] A muscle imbalance between an agonist and antagonist muscle can occur due to a neurological disorder, spinal cord injury, and our lifestyle/postural habits.[1] A decrease in muscle tone leads to continuous disuse and eventually muscular atrophy. The constant contraction of the agonist muscle with minimal resistance can result in a contracture. ## Treatment[edit] ### Passive stretching[edit] Typically performed by physical therapists, passive stretching is a more beneficial preventative measure and tool to maintain available range of motion (ROM) rather than used as a treatment.[2] It is very important to continually move the limb throughout its full range at a specific velocity but a passive stretch can’t be maintained for the period of time required for optimal benefit. A 2017 Cochrane review found that stretching does not provide any short-term pain relief.[3] ### Splinting[edit] A contracture corrective device (CCD) is a dynamic splint that provides a continuous stretch with a continuous force and operates based on the principles of creep.[1] It is the most advantageous splint but more research is required. Splints are used in long term treatments and must be removed in order to stretch the antagonist muscle to maintain range of motion (passive stretching). ### Electrical stimulation[edit] Electrical stimulation improves passive range of motion but only temporarily.[1] Once the treatment is withdrawn, all benefits are reduced. It can play a critical role in muscle atrophy prevention. ### Surgery[edit] Surgery is a solution to muscle shortening but other complications may arise. Following muscle lengthening surgery, force production and ROM is usually reduced due to the shift in sarcomere locations between a muscle's maximal and minimal length.[1] Shortening of the surgically lengthened muscle can re-occur. ## References[edit] 1. ^ a b c d e f Farmer, S.E; M. James (2001). "Contractures in orthopaedic and neurological conditions: a review of causes and treatment". Disability and Rehabilitation. 23 (13): 549–558. doi:10.1080/09638280010029930. PMID 11451189. 2. ^ Worland, R., Arredondo, J., Angles, F., Lopez-Jimenez, F., & Jessup, D. (1998). Home continuous passive motion machine versus professional physical therapy following total knee replacement. Journal of Arthroplasty, 784-787, doi:10.1016/S0883-5403(98)90031-6 3. ^ Harvey, Lisa A; Katalinic, Owen M; Herbert, Robert D; Moseley, Anne M; Lannin, Natasha A; Schurr, Karl (2017-01-09). "Stretch for the treatment and prevention of contractures". Cochrane Database of Systematic Reviews. 1: CD007455. doi:10.1002/14651858.cd007455.pub3. ISSN 1465-1858. PMC 6464268. PMID 28146605. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Muscle contracture	c0009917	28,582	wikipedia	https://en.wikipedia.org/wiki/Muscle_contracture	2021-01-18T18:47:06	{"mesh": ["D003286"], "umls": ["C0009917"], "wikidata": ["Q11602751"]}
Genetic condition involving facial, heart, blood and skeletal features Noonan syndrome Other namesMale Turner syndrome, Noonan-Ehmke syndrome, Turner-like syndrome, Ullrich-Noonan syndrome[1] A 12-year-old girl with Noonan syndrome. Typical webbed neck. Double structural curve with rib deformity. SpecialtyMedical genetics, pediatrics SymptomsMildly unusual facial features, short height, congenital heart disease, bleeding problems, skeletal malformations[1] ComplicationsLeukemia[1] Usual onsetPresent at birth[2] TypesType 1 to 6[3] CausesGenetic mutation (autosomal dominant)[1] Diagnostic methodSuspected based on symptoms, confirmed with genetic testing[4][2] Differential diagnosisCardiofaciocutaneous syndrome, Turner syndrome, Costello syndrome, neurofibromatosis type 1[2][3] TreatmentBased on the symptoms[3] MedicationGrowth hormone[3] PrognosisDepends on the severity of heart problems[3] Frequency1 in 100 (1 in 2,000 severe disease)[4] Noonan syndrome (NS) is a genetic disorder that may present with mildly unusual facial features, short height, congenital heart disease, bleeding problems, and skeletal malformations.[1] Facial features include widely spaced eyes, light-colored eyes, low-set ears, a short neck, and a small lower jaw.[1] Heart problems may include pulmonary valve stenosis.[1] The breast bone may either protrude or be sunken, while the spine may be abnormally curved.[1] Intelligence in the syndrome is often normal.[1] Complications of NS can include leukemia.[1] A number of genetic mutations can result in Noonan syndrome.[1] The condition may be inherited from a person's parents as an autosomal dominant condition or occur as a new mutation.[3][1] Noonan syndrome is a type of RASopathy, the underlying mechanism for which involves overactivation within the RAS/MAPK cell signaling pathway.[1] The diagnosis may be suspected based on symptoms, medical imaging, and blood tests.[2][4] Confirmation may be achieved with genetic testing.[2] No cure for NS is known.[5] Treatment is based on the symptoms and underlying problems, and extra support in school may be required.[3] Growth hormone therapy during childhood can increase an affected person's final height.[3] Long-term outcomes typically depend on the severity of heart problems.[3] An estimated 1 in 100 people are mildly affected by NS, while about 1 in 2,000 have a more severe form of the condition.[4] Males appear to be affected more often than females.[2] The condition was first described in 1883 and was named after American pediatric cardiologist Jacqueline Noonan, who described further cases in 1963.[2] ## Contents * 1 Signs and symptoms * 1.1 Head * 1.2 Skin * 1.3 Musculoskeletal * 1.4 Heart * 1.5 Lungs * 1.6 Gastrointestinal * 1.7 Genitourinary system * 1.8 Circulation * 1.9 Neurological * 2 Causes * 3 Diagnosis * 3.1 Before birth * 3.2 Differential diagnosis * 4 Management * 4.1 Anesthesia risk * 5 Prognosis * 6 History * 7 References * 8 External links ## Signs and symptoms[edit] Abnormal features of Noonan syndrome at the age of 3 months: Note the eyebrow slant and left-side eyelid dropping.[6] Abnormal features of Noonan syndrome at the age of 3 months: Note the low-set, posteriorly rotated, and abnormally formed ear.[6] The most common signs leading to the diagnosis of Noonan syndrome are unique facial characteristics and musculoskeletal features. The facial characteristics are most prominent in infancy, becoming less apparent with age in many people with Noonan syndrome.[7] ### Head[edit] Some of the characteristic features of Noonan syndrome include a large head with excess skin on the back of the neck, low hairline at the nape of the neck, high hairline at the front of the head, triangular face shape, broad forehead, and a short, webbed neck.[citation needed] In the eyes, hypertelorism (widely set eyes) is a defining characteristic, present in 95% of people with Noonan syndrome. This may be accompanied by epicanthal folds (extra fold of skin at the inner corner of the eye), ptosis (drooping of the eyelids), proptosis (bulging eyes), strabismus (inward or outward turning of the eyes), nystagmus (jerking movement of the eyes) and refractive visual errors. The nose may be small, wide, and upturned. The development of the ears and auditory system may be affected in people with Noonan's syndrome. This can result in low-set ears (in over 90%), backward-rotated ears (over 90%), thick helix (outer rim) of ear (over 90%), incomplete folding of ears, chronic otitis media (ear infections), and hearing loss. Development of the mouth may also be affected in Noonan syndrome. This can result in deeply grooved philtrum (top lip line) (over 90%), micrognathia (undersized lower jaw), high arched palate, articulation difficulties (teeth don't line up) which can lead to dental problems. Similar to the muscular manifestations above, in the mouth, poor tongue control may be observed. ### Skin[edit] Skin signs and symptoms in Noonan syndrome include lymphedema (lymph swelling of the extremities), keloid formation, excessive scar formation, hyperkeratosis (overdevelopment of outer skin layer), pigmented nevi (darkly pigmented skin spots), and connective tissue disease ### Musculoskeletal[edit] Abnormalities in the limbs and extremities may occur in Noonan syndrome. This may manifest as bluntly ended fingers, extra padding on fingers and toes, edema of the back of hands and tops of feet, and cubitus valgus (wide carrying angle of the elbows). For short stature, growth hormone is sometimes combined with IGF-1 (or as an alternative, IGF-1 as a stand-alone) can be used to achieve an increased height/final height quicker. The final adult height of individuals with Noonan syndrome is about 161–167 cm in males and 150–155 cm in females, which approaches the lower limit of normal.[8] Spinal abnormalities may be present up to 30% of the time and this may require surgery to correct in over 60% of these cases.[citation needed] Other musculoskeletal manifestations in Noonan syndrome are associated with undifferentiated connective-tissue disorders which can be associated with joint contractures (tightness) or joint hypermobility (looseness). Additional factors may present in the form of winging of the scapula, scoliosis, breast bone prominence (pectus carinatum), breast bone depression (pectus excavatum). Muscle abnormalities may present as hypotonia (low muscle tone), which may lead to lordosis (increased hollow in the back) due to poor abdominal muscle tone. ### Heart[edit] Noonan syndrome is the second most common syndromic cause of congenital heart disease. This includes pulmonary valvular stenosis (50–60%), atrial septal defects (10–25%), ventricular septal defects (5–20%) and hypertrophic cardiomyopathy (12–35%).[citation needed] ### Lungs[edit] Restrictive lung function has been reported in some people. ### Gastrointestinal[edit] A number of diverse gastrointestinal (GI) symptoms have been associated with Noonan syndrome. These include swallowing difficulties, low gut motility, gastroparesis (delayed gastric emptying), intestinal malrotation, and frequent or forceful vomiting. These digestive issues may lead to decreased appetite, failure to thrive from infancy to puberty (75%), and occasionally the need for a feeding tube. ### Genitourinary system[edit] In some males with Noonan syndrome, testicles do not descend (cryptorchidism). ### Circulation[edit] Lymphatic anomalies including Posterior cervical hygroma (webbed neck) and Lymphedema may present in people with Noonan syndrome. A number of bleeding disorders have been associated with Noonan syndrome, these include platelet dysfunction, Blood clotting disorders, partial deficiency of factor VIII:C, partial deficiency of factor XI:C, partial deficiency of factor XII:C, and an imbalance of plasminogen activator inhibitor type-1 (PAI-1) and tissue plasminogen activator (t-PA) activity.[citation needed] It has been associated with Von Willebrand disease, Amegakaryocytic thrombocytopenia (low platelet count), prolonged activated partial thromboplastin time, combined coagulation defects. When present, these Noonan-syndrome accompanying disorders can be associated with a predisposition to bruise easily, or hemorrhage. ### Neurological[edit] Occasionally, Chiari malformation (type 1),may occur, which can lead to hydrocephalus.[citation needed] Seizures have also been reported. ## Causes[edit] NS is typically inherited in an autosomal dominant pattern with variable expression. Recurrence in siblings and apparent transmission from parent to child has long suggested a genetic defect with autosomal dominant inheritance and variable expression. Mutations in the Ras/mitogen activated protein kinase signaling pathways are known to be responsible for about 70% of NS cases.[9] Persons with NS have up to a 50% chance of transmitting it to their offspring. The fact that an affected parent is not always identified for children with NS suggests several possibilities: 1. Manifestations could be so subtle as to go unrecognized (variable expressivity) 2. NS is heterogeneous, comprising more than one similar condition of differing causes, and some of these may not be inherited. 3. A high proportion of cases may represent new, sporadic mutations. Type Online Mendelian Inheritance in Man database Gene Year found Locus % of cases Description Refs. NS1 163950 PTPN11 2001 12q24.1 50% The PTPN11 gene encodes the protein tyrosine phosphatase SHP-2. This protein is a component of several intracellular signal transduction pathways involved in embryonic development that modulate cell division, differentiation, and migration, including one mediated by the epidermal growth factor receptor, which is important in the formation of the semilunar heart valves. Duplication of the chromosome region containing PTPN11 can also result in NS. [10] [11] NS2 605275 Unknown; autosomal recessive [12] NS3 609942 KRAS 2006 12p12.1 <5% [13] NS4 610733 SOS1 2006 2p21 10% Activating mutations in SOS1 can give rise to NS. SHP-2 and SOS1 positively regulate the Ras/MAP kinase pathway, suggesting that its dysregulation mediates NS development.[14] [15] NS5 611553 RAF1 2007 3p25 3–17% [16] Heterozygous mutations in NRAS, HRAS, BRAF, SHOC2, MAP2K1, MAP2K2, and CBL have also been associated with a smaller percentage of NS and related phenotypes.[17] A condition known as "neurofibromatosis-Noonan syndrome" is associated with neurofibromin.[18] ## Diagnosis[edit] NS can be confirmed genetically by the presence of any of the known mutations listed above. However, despite identification of 14 causative genes, the absence of a known mutation will not exclude the diagnosis, as more, as-yet-undiscovered genes can cause NS. Thus, the diagnosis of NS is still based on clinical features. In other words, it is made when a physician feels that a person has enough of the features to warrant the label. The principal values of making a genetic diagnosis are that it guides additional medical and developmental evaluations, it excludes other possible explanations for the features, and it allows more accurate recurrence risk estimates. With more genotype-phenotype correlation studies being performed, a positive genetic diagnosis will help the clinician to be aware of possible anomalies specific to that certain gene mutation. For example, an increase in hypertrophic cardiomyopathy is seen in people with a mutation of KRAS and an increased risk of juvenile myelomonocytic leukemia exists for a mutation of PTPN11. In the future, studies may lead to a targeted management of NS symptoms that depends on what genetic mutation a person has. ### Before birth[edit] Prenatal features that might lead physicians to consider a diagnosis of Noonan syndrome include cystic hygroma, increased nuchal translucency, pleural effusion, and edema.[19] ### Differential diagnosis[edit] While Turner syndrome has similarities with renal anomalies and developmental delay, Turner syndrome is only found in females and often expresses differently. In Turner syndrome, there is a lower incidence of developmental delays, left-sided heart defects are constant and the occurrence of renal abnormalities is much lower.[20] Other RASopathies * Watson syndrome \- Watson Syndrome has a number of similar characteristics with Noonan's Syndrome such as short stature, pulmonary valve stenosis, variable intellectual development, and skin pigment changes.[20][21] * Cardiofaciocutaneous (CFC) syndrome - CFC syndrome is very similar to Noonan's Syndrome due to similar cardiac and lymphatic features. However, In CFC syndrome intellectual disability and gastrointestinal problems are often more severe and pronounced.[20][22] * Costello syndrome \- Like CFC syndrome, Costello syndrome has overlapping features with Noonan's Syndrome. However, the conditions can be distinguished by their genetic cause.[23][24] * Neurofibromatosis 1 (NF1) [20][25] * Williams syndrome [20][26] ## Management[edit] The treatment varies depending on complications but tend to be quite standard, reflecting the treatment of the general population.[20] Management guidelines, divided by systems, including general, developmental, dental, growth and feeding, cardiovascular, audiological, haematological, renal and skeletal, that account for actions to be taken at diagnosis, after diagnosis and if symptomatic, have been published by an American consortium.[19] Specifically, treatment of cardiovascular complications resemble that of the general population and treatment of bleeding diathesis is guided by the specific factor deficiency or platelet aggregation.[20] * Neuropsychological testing is recommended to find strengths and challenges to tailor support needed for school and career. * Educational customization such as an individualized education program plan is sometimes needed for school-aged children. * Speech therapy if speech and articulation issues present * Physical therapy and occupational therapy for gross- and fine-motor delays * Hypotonia and motor difficulties often impact handwriting. Accommodations for lessening handwriting demands will improve performance and save long-term hand function. * Periodic follow up and lifelong monitoring of abnormalities found in any system, especially the cardiovascular system, is recommended.[27][8] ### Anesthesia risk[edit] Although a few people with Noonan syndrome have been reported to develop malignant hyperthermia, the gene mutation of diseases known to be associated with malignant hyperthermia is different than that of Noonan syndrome.[28] ## Prognosis[edit] The lifespan of people with Noonan's syndrome can be similar to the general population, however, Noonan syndrome can be associated with several health conditions that can contribute to mortality. The greatest contributor to mortality in individuals with Noonan syndrome is complications of cardiovascular disease.[29][8] Prognosis is therefore largely dependent on the presence or absence of cardiac disease, as well as the type and severity of the disease (if disease is present).[8] Most notably, Noonan syndrome with hypertrophic cardiomyopathy is associated with increased mortality.[29][8] ## History[edit] The oldest known case of NS, described in 1883 by Kobylinski Jacqueline Noonan was practicing as a pediatric cardiologist at the University of Iowa when she noticed that children with a rare type of heart defect, valvular pulmonary stenosis, often had a characteristic physical appearance, with short stature, webbed neck, wide spaced eyes, and low-set ears. Both boys and girls were affected. These characteristics were sometimes seen running in families but were not associated with gross chromosomal abnormalities. She studied 833 people with Noonan syndrome at the congenital heart disease clinic, looking for other congenital abnormalities, and in 1963 presented a paper: "Associated non-cardiac malformations in children with congenital heart disease".[30] This described 9 children who in addition to congenital heart disease had characteristic facial features, chest deformities and short stature. Dr. John Opitz, a former student of Dr. Noonan's, first began to call the condition "Noonan syndrome" when he saw children who looked like those whom Dr. Noonan had described. Dr. Noonan produced a paper titled "Hypertelorism with Turner Phenotype" in 1968 where she studied 19 patients who displayed symptoms indicative of Noonan's Syndrome.[31] In 1971 at the Symposium of Cardiovascular defects, the name 'Noonan syndrome' became officially recognized. ## References[edit] 1. ^ a b c d e f g h i j k l m "Noonan syndrome". Genetics Home Reference. Retrieved 24 December 2018. 2. ^ a b c d e f g "Noonan Syndrome". NORD (National Organization for Rare Disorders). 2016. Retrieved 24 December 2018. 3. ^ a b c d e f g h i "Noonan syndrome". Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. Retrieved 25 December 2018. 4. ^ a b c d Bhambhani V, Muenke M (January 2014). "Noonan syndrome". American Family Physician. 89 (1): 37–43. PMC 4099190. PMID 24444506. 5. ^ "Noonan Syndrome - Children's Health Issues". Merck Manuals Consumer Version. Retrieved 25 December 2018. 6. ^ a b Nosan G, Bertok S, Vesel S, Yntema HG, Paro-Panjan D (December 2013). "A lethal course of hypertrophic cardiomyopathy in Noonan syndrome due to a novel germline mutation in the KRAS gene: case study". Croatian Medical Journal. 54 (6): 574–8. doi:10.3325/cmj.2013.54.574. PMC 3893993. PMID 24382853. 7. ^ Romano, Alicia A.; Allanson, Judith E.; Dahlgren, Jovanna; Gelb, Bruce D.; Hall, Bryan; Pierpont, Mary Ella; Roberts, Amy E.; Robinson, Wanda; Takemoto, Clifford M.; Noonan, Jacqueline A. (October 2010). "Noonan syndrome: clinical features, diagnosis, and management guidelines". Pediatrics. 126 (4): 746–759. doi:10.1542/peds.2009-3207. ISSN 1098-4275. PMID 20876176. S2CID 11297756. 8. ^ a b c d e Allanson, Judith E.; Roberts, Amy E. (1993), Adam, Margaret P.; Ardinger, Holly H.; Pagon, Roberta A.; Wallace, Stephanie E. (eds.), "Noonan Syndrome", GeneReviews®, University of Washington, Seattle, PMID 20301303, retrieved 2019-11-18 9. ^ Razzaque MA, Komoike Y, Nishizawa T, Inai K, Furutani M, Higashinakagawa T, Matsuoka R (March 2012). "Characterization of a novel KRAS mutation identified in Noonan syndrome". American Journal of Medical Genetics. Part A. 158A (3): 524–32. doi:10.1002/ajmg.a.34419. PMID 22302539. S2CID 34135931. 10. ^ Tartaglia M, Mehler EL, Goldberg R, Zampino G, Brunner HG, Kremer H, et al. (December 2001). "Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome". Nature Genetics. 29 (4): 465–8. doi:10.1038/ng772. PMID 11704759. S2CID 14627986. 11. ^ Shchelochkov OA, Patel A, Weissenberger GM, Chinault AC, Wiszniewska J, Fernandes PH, et al. (April 2008). "Duplication of chromosome band 12q24.11q24.23 results in apparent Noonan syndrome". American Journal of Medical Genetics. Part A. 146A (8): 1042–8. doi:10.1002/ajmg.a.32215. PMID 18348260. S2CID 205309115. 12. ^ van Der Burgt I, Brunner H (September 2000). "Genetic heterogeneity in Noonan syndrome: evidence for an autosomal recessive form". American Journal of Medical Genetics. 94 (1): 46–51. doi:10.1002/1096-8628(20000904)94:1<46::AID-AJMG10>3.0.CO;2-I. PMID 10982482. 13. ^ Schubbert S, Zenker M, Rowe SL, Böll S, Klein C, Bollag G, et al. (March 2006). "Germline KRAS mutations cause Noonan syndrome". Nature Genetics. 38 (3): 331–6. doi:10.1038/ng1748. PMID 16474405. S2CID 8193354. 14. ^ Bentires-Alj M, Kontaridis MI, Neel BG (March 2006). "Stops along the RAS pathway in human genetic disease". Nature Medicine. 12 (3): 283–5. doi:10.1038/nm0306-283. PMID 16520774. S2CID 6989331. 15. ^ Roberts AE, Araki T, Swanson KD, Montgomery KT, Schiripo TA, Joshi VA, et al. (January 2007). "Germline gain-of-function mutations in SOS1 cause Noonan syndrome". Nature Genetics. 39 (1): 70–4. doi:10.1038/ng1926. PMID 17143285. S2CID 10222262. 16. ^ Razzaque MA, Nishizawa T, Komoike Y, Yagi H, Furutani M, Amo R, et al. (August 2007). "Germline gain-of-function mutations in RAF1 cause Noonan syndrome". Nature Genetics. 39 (8): 1013–7. doi:10.1038/ng2078. PMID 17603482. S2CID 29753972. 17. ^ "Download Catalog - Mayo Medical Laboratories". www.mayomedicallaboratories.com. 18. ^ De Luca A, Bottillo I, Sarkozy A, Carta C, Neri C, Bellacchio E, et al. (December 2005). "NF1 gene mutations represent the major molecular event underlying neurofibromatosis-Noonan syndrome". American Journal of Human Genetics. 77 (6): 1092–101. doi:10.1086/498454. PMC 1285166. PMID 16380919. 19. ^ a b Roberts, Amy E.; Allanson, Judith E.; Tartaglia, Marco; Gelb, Bruce D. (2013-01-26). "Noonan syndrome". Lancet. 381 (9863): 333–342. doi:10.1016/S0140-6736(12)61023-X. ISSN 1474-547X. PMC 4267483. PMID 23312968. 20. ^ a b c d e f g Allanson, Judith E.; Roberts, Amy E. (1993), Adam, Margaret P.; Ardinger, Holly H.; Pagon, Roberta A.; Wallace, Stephanie E. (eds.), "Noonan Syndrome", GeneReviews®, University of Washington, Seattle, PMID 20301303, retrieved 2019-11-25 21. ^ Allanson, J. E.; Upadhyaya, M.; Watson, G. H.; Partington, M.; MacKenzie, A.; Lahey, D.; MacLeod, H.; Sarfarazi, M.; Broadhead, W.; Harper, P. S. (November 1991). "Watson syndrome: is it a subtype of type 1 neurofibromatosis?". Journal of Medical Genetics. 28 (11): 752–756. doi:10.1136/jmg.28.11.752. ISSN 0022-2593. PMC 1017110. PMID 1770531. 22. ^ Armour, C. M.; Allanson, J. E. (April 2008). "Further delineation of cardio-facio-cutaneous syndrome: clinical features of 38 individuals with proven mutations". Journal of Medical Genetics. 45 (4): 249–254. doi:10.1136/jmg.2007.054460. ISSN 1468-6244. PMID 18039946. S2CID 9742395. 23. ^ Kerr, B.; Delrue, M.-A.; Sigaudy, S.; Perveen, R.; Marche, M.; Burgelin, I.; Stef, M.; Tang, B.; Eden, O. B.; O'Sullivan, J.; De Sandre-Giovannoli, A. (May 2006). "Genotype-phenotype correlation in Costello syndrome: HRAS mutation analysis in 43 cases". Journal of Medical Genetics. 43 (5): 401–405. doi:10.1136/jmg.2005.040352. ISSN 1468-6244. PMC 2564514. PMID 16443854. 24. ^ Gripp, Karen W.; Lin, Angela E.; Stabley, Deborah L.; Nicholson, Linda; Scott, Charles I.; Doyle, Daniel; Aoki, Yoko; Matsubara, Yoichi; Zackai, Elaine H.; Lapunzina, Pablo; Gonzalez-Meneses, Antonio (2006-01-01). "HRAS mutation analysis in Costello syndrome: Genotype and phenotype correlation". American Journal of Medical Genetics Part A. 140A (1): 1–7. doi:10.1002/ajmg.a.31047. ISSN 1552-4825. PMID 16329078. S2CID 27334655. 25. ^ Bertola, Debora R.; Pereira, Alexandre C.; Passetti, Fábio; de Oliveira, Paulo S.L.; Messiaen, Ludwine; Gelb, Bruce D.; Kim, Chong A.; Krieger, José Eduardo (2005-07-30). "Neurofibromatosis-Noonan syndrome: Molecular evidence of the concurrence of both disorders in a patient". American Journal of Medical Genetics Part A. 136A (3): 242–245. doi:10.1002/ajmg.a.30813. ISSN 1552-4825. PMID 15948193. S2CID 40235559. 26. ^ Morris, Colleen A. (1993), Adam, Margaret P.; Ardinger, Holly H.; Pagon, Roberta A.; Wallace, Stephanie E. (eds.), "Williams Syndrome", GeneReviews®, University of Washington, Seattle, PMID 20301427, retrieved 2019-11-25 27. ^ "Noonan syndrome - Symptoms, diagnosis and treatment \| BMJ Best Practice". bestpractice.bmj.com. Retrieved 2019-11-18. 28. ^ "Does Noonan Syndrome Increase Malignant Hyperthermia Susceptibility? - MHAUS". www.mhaus.org. Retrieved 2019-11-25. 29. ^ a b "DynaMed". www.dynamed.com. Retrieved 2019-11-11. 30. ^ Noonan JA, Ehmke DA (1963). "Associated noncardiac malformations in children with congenital heart disease". Midwest Soc Pediatr Res. 63: 468–70. 31. ^ Noonan, Jacqueline A. (1968-10-01). "Hypertelorism With Turner Phenotype: A New Syndrome With Associated Congenital Heart Disease". American Journal of Diseases of Children. 116 (4): 373–80. doi:10.1001/archpedi.1968.02100020377005. ISSN 0002-922X. PMID 4386970. ## External links[edit] Classification D * ICD-10: Q87.1 * ICD-9-CM: 759.89 * OMIM: 163950 605275 609942 610733 611553 * MeSH: D009634 * DiseasesDB: 29094 * SNOMED CT: 205824006 External resources * MedlinePlus: 001656 * eMedicine: article/947504 * Patient UK: Noonan syndrome * GeneReviews: Noonan Syndrome * Orphanet: 648 Wikimedia Commons has media related to Noonan syndrome. * v * t * e Congenital abnormality syndromes Craniofacial * Acrocephalosyndactylia * Apert syndrome * Carpenter syndrome * Pfeiffer syndrome * Saethre–Chotzen syndrome * Sakati–Nyhan–Tisdale syndrome * Bonnet–Dechaume–Blanc syndrome * Other * Baller–Gerold syndrome * Cyclopia * Goldenhar syndrome * Möbius syndrome Short stature * 1q21.1 deletion syndrome * Aarskog–Scott syndrome * Cockayne syndrome * Cornelia de Lange syndrome * Dubowitz syndrome * Noonan syndrome * Robinow syndrome * Silver–Russell syndrome * Seckel syndrome * Smith–Lemli–Opitz syndrome * Snyder–Robinson syndrome * Turner syndrome Limbs * Adducted thumb syndrome * Holt–Oram syndrome * Klippel–Trénaunay–Weber syndrome * Nail–patella syndrome * Rubinstein–Taybi syndrome * Gastrulation/mesoderm: * Caudal regression syndrome * Ectromelia * Sirenomelia * VACTERL association Overgrowth syndromes * Beckwith–Wiedemann syndrome * Proteus syndrome * Perlman syndrome * Sotos syndrome * Weaver syndrome * Klippel–Trénaunay–Weber syndrome * Benign symmetric lipomatosis * Bannayan–Riley–Ruvalcaba syndrome * Neurofibromatosis type I Laurence–Moon–Bardet–Biedl * Bardet–Biedl syndrome * Laurence–Moon syndrome Combined/other, known locus * 2 (Feingold syndrome) * 3 (Zimmermann–Laband syndrome) * 4/13 (Fraser syndrome) * 8 (Branchio-oto-renal syndrome, CHARGE syndrome) * 12 (Keutel syndrome, Timothy syndrome) * 15 (Marfan syndrome) * 19 (Donohue syndrome) * Multiple * Fryns syndrome * v * t * e Deficiencies of intracellular signaling peptides and proteins GTP-binding protein regulators GTPase-activating protein * Neurofibromatosis type I * Watson syndrome * Tuberous sclerosis Guanine nucleotide exchange factor * Marinesco–Sjögren syndrome * Aarskog–Scott syndrome * Juvenile primary lateral sclerosis * X-Linked mental retardation 1 G protein Heterotrimeic * cAMP/GNAS1: Pseudopseudohypoparathyroidism * Progressive osseous heteroplasia * Pseudohypoparathyroidism * Albright's hereditary osteodystrophy * McCune–Albright syndrome * CGL 2 Monomeric * RAS: HRAS * Costello syndrome * KRAS * Noonan syndrome 3 * KRAS Cardiofaciocutaneous syndrome * RAB: RAB7 * Charcot–Marie–Tooth disease * RAB23 * Carpenter syndrome * RAB27 * Griscelli syndrome type 2 * RHO: RAC2 * Neutrophil immunodeficiency syndrome * ARF: SAR1B * Chylomicron retention disease * ARL13B * Joubert syndrome 8 * ARL6 * Bardet–Biedl syndrome 3 MAP kinase * Cardiofaciocutaneous syndrome Other kinase/phosphatase Tyrosine kinase * BTK * X-linked agammaglobulinemia * ZAP70 * ZAP70 deficiency Serine/threonine kinase * RPS6KA3 * Coffin-Lowry syndrome * CHEK2 * Li-Fraumeni syndrome 2 * IKBKG * Incontinentia pigmenti * STK11 * Peutz–Jeghers syndrome * DMPK * Myotonic dystrophy 1 * ATR * Seckel syndrome 1 * GRK1 * Oguchi disease 2 * WNK4/WNK1 * Pseudohypoaldosteronism 2 Tyrosine phosphatase * PTEN * Bannayan–Riley–Ruvalcaba syndrome * Lhermitte–Duclos disease * Cowden syndrome * Proteus-like syndrome * MTM1 * X-linked myotubular myopathy * PTPN11 * Noonan syndrome 1 * LEOPARD syndrome * Metachondromatosis Signal transducing adaptor proteins * EDARADD * EDARADD Hypohidrotic ectodermal dysplasia * SH3BP2 * Cherubism * LDB3 * Zaspopathy Other * NF2 * Neurofibromatosis type II * NOTCH3 * CADASIL * PRKAR1A * Carney complex * PRKAG2 * Wolff–Parkinson–White syndrome * PRKCSH * PRKCSH Polycystic liver disease * XIAP * XIAP2 See also intracellular signaling peptides and proteins Authority control * GND: 4171991-8 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Noonan syndrome	c0028326	28,583	wikipedia	https://en.wikipedia.org/wiki/Noonan_syndrome	2021-01-18T19:07:07	{"gard": ["10955"], "mesh": ["D009634"], "umls": ["C0028326"], "icd-9": ["759.89"], "orphanet": ["648"], "wikidata": ["Q1543446"]}
A number sign (#) is used with this entry because of evidence that eosinophil peroxidase deficiency (EXPD) is caused by homozygous or compound heterozygous mutation in the EPX gene (131399) on chromosome 17q22. Description Eosinophil peroxidase deficiency is a rare abnormality of eosinophil granulocytes characterized by decreased or absent peroxidase activity and decreased volume of the granule matrix (summary by Romano et al., 1994). Nakagawa et al. (2001) noted that there are no clinical symptoms and the diagnosis is made solely by cytochemical analysis. Clinical Features In Yemenite Jews in Israel, Presentey (1969) and Presentey and Szapiro (1969) described a 'new' anomaly of eosinophils characterized by nuclear hypersegmentation, hypogranulation, and negative peroxidase and phospholipid staining. Lepelley et al. (1987) described the Presentey anomaly in twin sisters; one had refractory anemia, which may have been coincidental and merely the symptom that brought the twins to attention. In contrast to myeloperoxidase deficiency (254600), in which all neutrophils and monocytes are affected, isolated deficiency of eosinophil peroxidase is very rare (Presentey (1970, 1984); Presentey and Joshua, 1982; Schaeffer et al., 1977). Hoffmann and Tielens (1987) reported the case of an affected 4-year-old boy of Turkish ancestry whose parents were 'consanguineous in the second degree.' Hoffmann and Tielens (1987) commented on the fact that the use of automated flow-cytochemical analyzers in the hematology laboratory had stimulated interest in peroxidase activity of granulocytes and brought many cases of hereditary and acquired deficiency to attention. It was in this way that their case was detected. Valdes and Calero (1987) described a patient with deficiency of eosinophil peroxidase detected by flow cytochemistry. Electron microscopic analyses of peroxidase-deficient eosinophils showed an increase in the ratio between the size of the matrix and the core of the specific granules (Lepelley et al., 1987; Lejeune et al., 1988). Zabucchi et al. (1992) found 5 eosinophil peroxidase-deficient subjects among 131,000 peripheral blood samples examined by routine automated methods. All met the main criteria: absent or strongly decreased reaction for peroxidase, absent or strongly decreased staining with Sudan Black, and an increased ratio of the granule core volume to the total granule volume. Zabucchi et al. (1992) demonstrated that the increased core-matrix ratio was caused mainly by a decrease of the volume of the matrix and that 2 other matrix proteins, eosinophil cationic protein (131398) and eosinophil-derived neurotoxin (131410), appeared to be present in normal amounts. Nakagawa et al. (2001) reported a 62-year-old man who was found to have EPO deficiency during routine peripheral blood testing for investigation of colon polyps; he had no history of recurrent infection or allergy. Inheritance In the patients with eosinophil peroxidase deficiency reported by Presentey (1969) and Presentey and Szapiro (1969), recessive inheritance seemed quite clear. Molecular Genetics In a man with eosinophil peroxidase deficiency, Romano et al. (1994) identified compound heterozygosity for mutations in the EPX gene (131399.0001-131399.0002). In a man with eosinophil peroxidase deficiency, Nakagawa et al. (2001) identified homozygosity for a mutation in the EPX gene (131399.0003). His wife carried homozygous wildtype alleles, whereas his son and daughter were heterozygous for the mutation. Cytochemical blood analysis in his children showed a completely normal display. INHERITANCE \- Autosomal recessive LABORATORY ABNORMALITIES \- Decreased or absent peroxidase activity \- Decreased volume of the granule matrix \- Eosinophil nuclear hypersegmentation, hypogranulation, and negative peroxidase and phospholipid staining \- Increase in the ratio between the size of the matrix and the core of the specific granules seen on EM MISCELLANEOUS \- No clinical manifestations MOLECULAR BASIS \- Caused by mutation in the eosinophil peroxidase gene (EPX, 131399.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	EOSINOPHIL PEROXIDASE DEFICIENCY	c1850000	28,584	omim	https://www.omim.org/entry/261500	2019-09-22T16:23:33	{"mesh": ["C564893"], "omim": ["261500"], "synonyms": ["Alternative titles", "EOSINOPHIL PEROXIDASE DEFICIENCY, PARTIAL", "PEROXIDASE AND PHOSPHOLIPID DEFICIENCY IN EOSINOPHILS", "PRESENTEY ANOMALY"]}
Budd-Chiari syndrome (BCS) is caused by obstruction of hepatic venous outflow involving either the hepatic veins or the terminal segment of the inferior vena cava. ## Epidemiology Prevalence remains largely unknown but estimates range between 1/50,000 and 1/100,000. ## Clinical description The obstruction leads to hepatic congestion and ischemic necrosis. Severity depends on the speed of onset and extent of the obstruction. Obstructions are generally caused by thrombosis (primary BCS). With time, thrombi reorganise to form a fibrous tissue that leads either to localised stenosis of the thrombotic vein or to diffuse obliteration resulting in its transformation into fibrous cords. Localised stenoses may present as the appearance of a membrane-like structure. Secondary BCS results from tumour invasion into the lumen or compression of the vein by an expansive lesion. The principle manifestations of BCS are ascites (which are often massive and intractable) leading to undernutrition and renal insufficiency, gastrointestinal haemorrhage due to portal hypertension, and hepatic insufficiency resulting in encephalopathy and severe infections. However, asymptomatic forms have also been reported. ## Etiology Primary BCS is associated with a combination of factors that lead to a susceptibility for venous thrombosis: primary myeloproliferative syndromes (present in 50% of cases and manifesting as a 'forme fruste' or atypical forms of the disease, but identified through detection of a mutation in the JAK2 gene), Factor V Leiden thrombophilia, protein C deficiency, antiphospholipid syndrome, Behcet disease, paroxysmal nocturnal haemoglobinuria (see these terms), use of oestrogen-progesterone oral contraceptives and inflammatory colitis. ## Diagnostic methods Diagnosis can usually be established by non-invasive means through imaging of the hepatic veins and the inferior vena cava (Doppler ultrasound, tomodensitometry and MRI) but requires a radiologist with sufficient experience and with an awareness of the potential diagnosis. Hepatic venography or cavography, and liver puncture biopsy are not usually necessary. ## Management and treatment Treatment approaches include correction of the factors leading to an increased risk of thrombosis, long term anticoagulant therapy, recanalisation of the obstructed veins by interventional radiology, TIPS (transjugular intrahepatic portosystemic shunt) and liver transplantation in case failure of other treatment methods. ## Prognosis The natural course of the disease is very severe (less than 10% of patients survive for more than 3 years without treatment). At present, when the diagnosis is made quickly and treatment is initiated rapidly, the survival rate is 90% at 5 years. The long term prognosis depends on the associated risk factors for thrombosis. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Budd-Chiari syndrome	c0856761	28,585	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=131	2021-01-23T18:32:56	{"gard": ["5968"], "mesh": ["D006502"], "omim": ["600880"], "umls": ["C0019154", "C0856761"], "icd-10": ["I82.0"]}
Pachydermodactyly is a superficial dermal fibromatosis that presents as a poorly circumscribed symmetric, infiltrative, asymptomatic soft-tissue hypertrophy of the proximal fingers, typically sparing the thumbs and fifth fingers and rarely extending proximally to the wrists or occurring distally.[1]:990 ## See also[edit] * Skin lesion ## References[edit] 1. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0. ## External links[edit] * A Case of Pachydermodactyly This Dermal and subcutaneous growths article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Pachydermodactyly	c0406574	28,586	wikipedia	https://en.wikipedia.org/wiki/Pachydermodactyly	2021-01-18T18:53:52	{"umls": ["C0406574"], "wikidata": ["Q7122119"]}
Human disease Posterior amorphous corneal dystrophy SpecialtyOphthalmology Posterior amorphous corneal dystrophy (PACD) is a rare form of corneal dystrophy. It is not yet linked to any chromosomal locus. The first report describing this dystrophy dates back to 1977.[1] ## References[edit] 1. ^ Carpel EF, Sigelman RJ, Doughman DJ (May 1977). "Posterior amorphous corneal dystrophy". Am. J. Ophthalmol. 83 (5): 629–32. doi:10.1016/0002-9394(77)90127-1. PMID 301356. ## External links[edit] Classification D * OMIM: 612868 * MeSH: C567546 C567546, C567546 * v * t * e Types of corneal dystrophy Epithelial and subepithelial * Epithelial basement membrane dystrophy * Gelatinous drop-like corneal dystrophy * Lisch epithelial corneal dystrophy * Meesmann corneal dystrophy * Subepithelial mucinous corneal dystrophy Bowman's membrane * Reis–Bucklers corneal dystrophy * Thiel-Behnke dystrophy Stroma * Congenital stromal corneal dystrophy * Fleck corneal dystrophy * Granular corneal dystrophy * Lattice corneal dystrophy * Macular corneal dystrophy * Posterior amorphous corneal dystrophy * Schnyder crystalline corneal dystrophy Descemet's membrane and endothelial * Congenital hereditary endothelial dystrophy * Fuchs' dystrophy * Posterior polymorphous corneal dystrophy * X-linked endothelial corneal dystrophy This article about the eye is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Posterior amorphous corneal dystrophy	c2748502	28,587	wikipedia	https://en.wikipedia.org/wiki/Posterior_amorphous_corneal_dystrophy	2021-01-18T18:56:19	{"mesh": ["C567546"], "umls": ["C2748502"], "orphanet": ["98971"], "wikidata": ["Q4183962"]}
## Inheritance From a study of 100 monozygotic twin pairs, 99 dizygotic twin pairs, and 99 unrelated randomly paired age-matched German subjects, Larsson et al. (2003) concluded that variations in characteristic patterns of the human iris are under strong genetic influence. Stellate pattern of the iris is characteristic of Williams syndrome (194050) and the Lester sign of nail-patella syndrome (161200). Neither of these is completely specific to the genetic syndrome, but both occur in low frequency in the general population. Mapping Larsson et al. (2011) performed genomewide association scans on 4 iris characteristics (crypt frequency, furrow contractions, presence of peripupillary pigmented ring, and number of nevi) in a total of 2,693 individuals in 3 Australian samples of European descent. They found evidence for association between crypt frequency and a SNP (rs10235789) in intron 6 of the axonal guidance gene SEMA3A on chromosome 7q21.11 (603961; combined p = 6.6 x 10(-11)); approximately 1.5% of the variance for crypts could be explained by the replicated SNP findings with rs10235789. They also found association between furrow contractions and a nonsynonymous coding SNP (rs3739070) within the cytoskeleton gene TRAF3IP1 on chromosome 2q37.3 (607380; combined p = 2.3 x 10(-12)); approximately 1.7% of variance in the discovery sample and 3% in the first replication sample were explained by rs3739070. In addition, association was found between the pigmented ring and a SNP (rs4900109) located in an intergenic region on chromosome 14q32.12 upstream of the pigmentation gene SLC24A4 (609840); rs4900109 is in high linkage disequilibrium with a SNP in SLC24A4, rs12896399 (609840.0001), that has been associated with multiple pigment-related phenotypes, including blue versus brown eye color and blue versus green eye color. Larsson et al. (2011) suggested that rs40900109 may influence where in the iris the pigment is placed, rather than overall eye color per se. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	IRIS PATTERN	c1853115	28,588	omim	https://www.omim.org/entry/610744	2019-09-22T16:04:10	{"omim": ["610744"]}
Joint abnormality Hip dysplasia Other namesDevelopmental dysplasia of the hip (DDH),[1] developmental dislocation of the hip,[1] congenital dysplasia of the hip (CDH)[2] Congenital dislocation of the left hip in an elderly person. Closed arrow marks the acetabulum, open arrow the femoral head. SpecialtyPediatrics, orthopedics SymptomsNone, one leg shorter, limping[1] ComplicationsArthritis[3] Risk factorsFamily history, swaddling, breech birth[3] Diagnostic methodPhysical exam, ultrasound[3] TreatmentBracing, casting, surgery[3] PrognosisGood (if detected early)[1] Frequency1 in 1,000 (term babies)[3] Hip dysplasia is an abnormality of the hip joint where the socket portion does not fully cover the ball portion, resulting in an increased risk for joint dislocation.[1] Hip dysplasia may occur at birth or develop in early life.[1] Regardless, it does not typically produce symptoms in babies less than a year old.[3] Occasionally one leg may be shorter than the other.[1] The left hip is more often affected than the right.[3] Complications without treatment can include arthritis, limping, and low back pain.[3] Risk factors for hip dysplasia include family history, certain swaddling practices, and breech birth.[3] If one identical twin is affected, there is a 40% risk the other will also be affected.[3] Screening all babies for the condition by physical examination is recommended.[3] Ultrasonography may also be useful.[3] Many of those with mild instability resolve without specific treatment.[3] In more significant cases, if detected early, bracing may be all that is required.[3] In cases that are detected later, surgery and casting may be needed.[3] About 7.5% of hip replacements are done to treat problems which have arisen from hip dysplasia.[3] About 1 in 1,000 babies have hip dysplasia.[3] Hip instability of meaningful importance occurs in one to two percent of babies born at term.[3] Females are affected more often than males.[1] Hip dysplasia was described at least as early as the 300s BC by Hippocrates.[4] ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Congenital * 2.2 Acquired * 3 Diagnosis * 3.1 Terminology * 3.2 Imaging * 4 Treatment * 4.1 Harnesses, casts, and traction * 4.2 Surgery * 4.2.1 Hip replacement and osteotomy * 5 Epidemiology * 6 History * 7 Society and culture * 8 Research * 9 Other animals * 10 Notes * 11 References * 12 External links ## Signs and symptoms[edit] Types of misalignments of femur head to socket in hip dysplasia. A: Normal. B: Dysplasia. C: Subluxation. D: Luxation Hip dysplasia can range from barely detectable to severely malformed or dislocated. The congenital form, teratologic or non-reducible dislocation occurs as part of more complex conditions.[citation needed] The condition can be bilateral or unilateral: * If both hip joints are affected, one speaks of "bilateral" dysplasia. In this case, some diagnostic indicators like asymmetric folds and leg-length inequality do not apply. * In unilateral dysplasia only one joint shows deformity, the contralateral side may show resulting effects.[5] In the majority of unilateral cases, the left hip has the dysplasia. If the joint is fully dislocated a false acetabulum often forms (often higher up on the pelvis) opposite the dislocated femoral head position. In acetabular dysplasia, the acetabulum (socket) is too shallow or deformed. The center-edge angle is measured as described by Wiberg.[6] Two forms of femoral dysplasia are coxa vara, in which the femur head grows at too narrow an angle to the shaft, and coxa valga, in which the angle is too wide. A rare type, the "Beukes familial hip dysplasia" is found among Afrikaners that are members of the Beukes family. The femur head is flat and irregular. People develop osteoarthritis at an early age.[7] ## Causes[edit] Hip dysplasia is considered to be a multifactorial condition. That means that several factors are involved in causing the condition to manifest.[8] The cause of this condition is unknown; however, some factors of congenital hip dislocation are through heredity and racial background. It is also thought that the higher rates in some ethnic groups (such as some Native American groups) is due to the practice of swaddling of infants, which is known to be a potential risk factor for developing dysplasia. It also has a low risk in African Americans and southern Chinese.[citation needed] ### Congenital[edit] Some studies suggest a hormonal link.[9] Specifically, the hormone relaxin has been indicated.[10] A genetic factor is indicated since the trait runs in families and there is an increased occurrence in some ethnic populations (e.g., Native Americans,[11] Lapps[12] / Sami people[13]). A locus has been described on chromosome 13.[14] Beukes familial dysplasia, on the other hand, was found to map to an 11-cM region on chromosome 4q35, with nonpenetrant carriers not affected.[15] ### Acquired[edit] As an acquired condition it has often been linked to traditions of swaddling infants,[16] use of overly restrictive baby seats, carriers and other methods of transporting babies,[17] or use of a cradle board which locks the hip joint in an "adducted" position (pulling the knees together tends to pull the heads of the femur bone out of the sockets or acetabulae) for extended periods. Modern swaddling techniques, such as the 'hip healthy swaddle' have been developed to relieve stress on hip joints caused by traditional swaddling methods.[18] Further risk factors include breech birth, gender, genetics (family history),[19][20] and firstborns.[21] In breech position the femoral head tends to get pushed out of the socket. A narrow uterus also facilitates hip joint dislocation during fetal development and birth.[citation needed] ## Diagnosis[edit] α and β angles used in hip ultrasound Hip ultrasound X-Ray Image showing hip dysplasia in a baby Most countries have standard newborn exams that include a hip joint exam screening for early detection of hip dysplasia. Sometimes during an exam a "click" or more precisely "clunk" in the hip may be detected[22] (although not all clicks indicate hip dysplasia).[23] When a hip click (also known as "clicky hips" in the UK) is detected, the child's hips are tracked with additional screenings[24] to determine if developmental dysplasia of the hip is caused.[25] Two maneuvers commonly employed for diagnosis in neonatal exams are the Ortolani maneuver and the Barlow maneuver.[26][27] In order to do the Ortolani maneuver it is recommended that the examiner put the newborn baby in a position in which the contralateral hip is held still while the thigh of the hip being tested is abducted and gently pulled anteriorly. If a "clunk" is heard (the sound of the femoral head moving over the acetabulum), the joint is normal, but absence of the "clunk" sound indicates that the acetabulum is not fully developed. The next method that can be used is called the Barlow maneuver. It is done by adducting the hip while pushing the thigh posteriorly. If the hip goes out of the socket it means it is dislocated, and the newborn has a congenital hip dislocation. The baby is laid on its back for examination by separation of its legs. If a clicking sound can be heard, it indicates that the baby may have a dislocated hip. It is highly recommended that these maneuvers be done when the baby is not fussing, because the baby may inhibit hip movement. Asymmetrical gluteal folds and an apparent limb-length inequality can further indicate unilateral hip dysplasia.[28] Most vexingly, many newborn hips show a certain ligamentous laxity, on the other hand severely malformed joints can appear stable. That is one reason why follow-up exams and developmental monitoring are important. Frequency and methods of routine screenings in children is still in debate however physical examination of newborns followed by appropriate use of hip ultrasound is widely accepted.[29] The Harris hip score[30] (developed by William H. Harris MD, an orthopedist from Massachusetts) is one way to evaluate hip function following surgery. Other scoring methods are based on patients' evaluation like e.g. the Oxford hip score, HOOS and WOMAC score.[31] Children's Hospital Oakland Hip Evaluation Scale (CHOHES) is a modification of the Harris hip score that is currently being evaluated.[32] Hip dysplasia can develop in older age. Adolescents and adults with hip dysplasia may present with hip pain and in some cases hip labral tears. X-rays are used to confirm a diagnosis of hip dysplasia. CT scans and MRI scans are occasionally used too.[33][34] ### Terminology[edit] Some sources prefer "developmental dysplasia of the hip" (DDH) to "congenital dislocation of the hip" (CDH), finding the latter term insufficiently flexible in describing the diversity of potential complications.[35] The use of the word congenital can also imply that the condition already exists at birth. This terminology introduces challenges, because the joint in a newborn is formed from cartilage and is still malleable, making the onset difficult to ascertain.The newer term DDH also encompasses occult dysplasia (e.g. an underdeveloped joint) without dislocation and a dislocation developing after the "newborn" phase.[citation needed] The term is not used consistently. In pediatric/neonatal orthopedics it is used to describe unstable/dislocatable hips and poorly developed acetabula. For adults it describes hips showing abnormal femur head or acetabular x-rays.[36][37] Some sources prefer the term "hip dysplasia" over DDH, considering it to be "simpler and more accurate", partly because of the redundancy created by the use of the terms developmental and dysplasia.[38] Types of DDH include subluxation, dysplasia, and dislocation. The main types are the result of either laxity of the supporting capsule or an abnormal acetabulum. ### Imaging[edit] See also: X-ray of hip dysplasia ACR Appropriateness Criteria for hip dysplasia[39] Age Scenario Usual appropriate initial imaging <4 weeks Equivocal physical examination or risk factors No imaging Physical findings of DDH Ultrasonography 4 weeks - 4 months Equivocal physical examination or risk factors Ultrasonography 4 - 6 months Concern for DDH X-ray. Ultrasonography may be appropriate[notes 1] >6 months X-ray Hip dysplasia diagnosed by ultrasound[40] and projectional radiography ("X-ray").[41] Ultrasound imaging is generally preferred at up to 4 months due to limited ossification of the skeleton.[39][notes 1] Despite the widespread of ultrasound, pelvis X-ray is still frequently used to diagnose or monitor hip dysplasia or for assessing other congenital conditions or bone tumors.[42] The most useful lines and angles that can be drawn in the pediatric pelvis assessing hip dysplasia are as follows:[42] Different measurements are used in adults.[42] * Normal hip.[42] * Hip dysplasia.[42] ## Treatment[edit] Hip dysplasia presents a nearly perfect equilibrium between the arthritis, movement/mobility problems and pain associated with the developmental malformation, and the arthritis, movement/mobility problems and pain that are, as often as not in moderate to severe cases, inflicted by the treatment itself.[citation needed] However, given the very real possibility of a limp, constant and/or debilitating pain, complicated treatment and impaired mobility later in life, careful developmental monitoring is indicated and early intervention is often the best result. The worst possible consequence of non treatment is developing early arthritis, sometimes even during teenage years. All treatment aims to delay the onset of arthritis, but no treatment is fully successful in avoiding it; and, all available treatments bear the risk of inflicting equivalent damage. Most unfortunately, studies have as yet been unable to find a method of predicting outcomes in either the surgical/orthopedic treatment of the condition in infants and young children, or the surgical treatment of these early treatments' negative outcomes later in life (such as arthritis, avascular necrosis, trochanteric bursitis, and bone spurs of up to 2.5 cm just medial of the gluteus maximus insertion point on the greater trochanter due to excessive friction).[citation needed] ### Harnesses, casts, and traction[edit] Early hip dysplasia can often be treated using a Pavlik harness[43] (see photograph) or the Frejka pillow/splint[44] in the first year of life with usually normal results. Complications can occur when using the Pavlik harness. Cases of femoral nerve palsy[45] and avascular necrosis of the femoral head have been reported with the use of the Pavlik harness,[46] but whether these cases were due to improper application of the device or a complication encountered in the course of the disorder remains unresolved. Complications arise mainly because the sheet of the iliopsoas muscle pushes the circumflex artery[specify] against the neck of the femur and decreases blood flow to the femoral head, so the Frejka pillow is not indicated in all the forms of the developmental dysplasia of the hip.[citation needed] * Baby wearing a Pavlik harness * Diagram of Pavlik harness * Diagram of Frejka pillow * Traction Other devices employed include the spica cast,[47] particularly following surgical closed reduction, open reduction, or osteotomy in babies and young children. Traction is sometimes used in the weeks leading up to a surgery to help stretch ligaments in the hip joint, although its use is controversial and varies amongst physicians.[48] ### Surgery[edit] In older children the adductor and iliopsoas muscles may have to be treated surgically because they adapt to the dislocated joint position (contracture). Braces and splints are often used following either of these methods to continue treatment. Although some children "outgrow" untreated mild hip dysplasia[37] and some forms of untreated dysplasia cause little or no impairment of quality of life, studies have as yet been unable to find a method of predicting outcomes. On the other hand, it has often been documented that starting treatment late leads to complications and ends in poor results.[citation needed] #### Hip replacement and osteotomy[edit] Hip dysplasia is often cited as causing osteoarthritis of the hip at a comparatively young age. Dislocated load bearing surfaces lead to increased and unusual wear, although there are studies that contradict these findings (see [49][50]). Peri-acetabular osteotomy (PAO) surgery can be used to realign the hip joint in some adolescents and adults. Subsequent treatment with total hip arthroplasty (hip replacement) is complicated by a need for revision surgery (replacing the artificial joint) owing to skeletal changes as the body matures, loosening/wear or bone resorption. Hip resurfacing is another option for correcting hip dysplasia in adults. It is a type of hip replacement that preserves more bone, and may work for younger hip dysplasia patients.[51] Osteotomies are either used in conjunction with arthroplasty or by themselves to correct misalignment.[citation needed] ## Epidemiology[edit] Determining the incidence can be difficult.[52][53] In addition there is a wide margin in diagnostic results. A German study comparing two methods resulted in twice the usual rate for one method. The condition is eight times more frequent in females than in males.[9] Native Americans are more likely to have congenital hip dislocation than any of the other races. The risk for Native Americans is about 25-50 in 1000. The overall frequency of developmental dysplasia of the hip is approximately 1 case per 1000 individuals; however, Barlow believed that the incidence of hip instability in newborns can be as high as 1 case for every 60 newborns,[54] with the rate dropping to 1:240 at one week.[55] ## History[edit] The Frejka pillow splint was named after Dr. Bedrich Frejka (1890-1972), a Czech orthopedic surgeon. The Pavlik harness was named after Dr. Arnold Pavlik (1902-1962), also a Czech orthopedic surgeon.[citation needed] ## Society and culture[edit] In the television program ER, Kerry Weaver uses a crutch owing to congenital hip dysplasia. In season 12, she undergoes a hip replacement to cure her dysplasia when her previously untreated joint worsens.[56] ## Research[edit] One avenue of research is using stem cells. They are applied in grafting (bone grafting) or by seeding porous arthroplasty prosthesis with autologous fibroblasts or chondrocyte progenitor cells to assist in firmly anchoring the artificial material in the bone bed.[citation needed] ## Other animals[edit] Main article: Hip dysplasia (canine) In dogs, hip dysplasia is an abnormal formation of the hip socket that, in its more severe form, can eventually cause crippling lameness and painful arthritis of the joints. It is a genetic (polygenic) trait that is affected by environmental factors. It is common in many dog breeds, particularly the larger breeds.[citation needed] Hip dysplasia is one of the most studied veterinary conditions in dogs, and the most common single cause of arthritis of the hips.[57] Cats are also known to have this condition, especially Siamese.[58] ## Notes[edit] 1. ^ a b Ultrasonography is the imaging method of choice up to 6 months for the nonoperative surveillance imaging in harness of known diagnosis of DDH. \- "ACR Appropriateness Criteria - Developmental Dysplasia of the Hip (DDH)–Child". American College of Radiology. Revised 2018 ## References[edit] 1. ^ a b c d e f g h "Your Orthopaedic Connection: Developmental Dysplasia of the Hip". October 2013. 2. ^ "Definition: congenital dysplasia of the hip from Online Medical Dictionary".[dead link] 3. ^ a b c d e f g h i j k l m n o p q r Shaw, BA; Segal, LS; SECTION ON, ORTHOPAEDICS. (December 2016). "Evaluation and Referral for Developmental Dysplasia of the Hip in Infants". Pediatrics. 138 (6): e20163107. doi:10.1542/peds.2016-3107. PMID 27940740. 4. ^ Bentley, George (2009). European Instructional Lectures: Volume 9, 2009; 10th EFORT Congress, Vienna, Austria. Springer Science & Business Media. p. 40. ISBN 9783642009662. 5. ^ Jacobsen S, Rømer L, Søballe K (2006). "The other hip in unilateral hip dysplasia". Clin. Orthop. Relat. Res. 446: 239–46. doi:10.1097/01.blo.0000201151.91206.50. PMID 16721954. S2CID 11709860. 6. ^ Wiberg G. Studies of acetabular and congenital subluxation of the hip joint with special reference to complication of osteoarthritis Acta Chir Scand 1939, 83(Suppl. 58) 7. ^ Cilliers HJ, Beighton P (1990). "Beukes familial hip dysplasia: an autosomal dominant entity". Am. J. Med. Genet. 36 (4): 386–90. doi:10.1002/ajmg.1320360403. PMID 2389793. 8. ^ Lynn T Staheli, Fundamentals of Pediatric Orthopedics, p 13 9. ^ a b "Clinical Practice Guideline: Early Detection of Developmental Dysplasia of the Hip -- Committee on Quality Improvement and Subcommittee on Developmental Dysplasia of the Hip 105 (4): 896 -- AAP Policy". 29 January 2005. Archived from the original on 29 January 2005. 10. ^ Forst J, Forst C, Forst R, Heller KD (1997). "Pathogenetic relevance of the pregnancy hormone relaxin to inborn hip instability". Arch Orthop Trauma Surg. 116 (4): 209–12. doi:10.1007/BF00393711. PMID 9128773. S2CID 32322656. 11. ^ (PDF). 26 July 2011 https://web.archive.org/web/20110726005636/http://fds.oup.com/www.oup.co.uk/pdf/0-19-263161-6.pdf. Archived from the original (PDF) on 26 July 2011. Missing or empty `\|title=` (help) 12. ^ The occurrence of hip joint dislocation in early Lappic populations of Norway, Per Holck, Anthropological Department, Anatomical Institute, Box 1105 Blindern, N-0317 Oslo 3, Norway 13. ^ Forsdahl A (2000). "[A physician from Finnmark who pointed out the significance of heredity in congenital hip dysplasia]". Tidsskr. Nor. Legeforen. (in Norwegian). 120 (22): 2672–3. PMID 11077514. 14. ^ Mabuchi A, Nakamura S, Takatori Y, Ikegawa S (2006). "Familial osteoarthritis of the hip joint associated with acetabular dysplasia maps to chromosome 13q". Am. J. Hum. Genet. 79 (1): 163–8. doi:10.1086/505088. PMC 1474113. PMID 16773577. 15. ^ "AJHG - Autosomal Dominant (Beukes) Premature Degenerative Osteoarthropathy of the Hip Joint Maps to an 11-cM Region on Chromosome 4q35". 6 May 2008. Archived from the original on 6 May 2008. 16. ^ Mahan ST, Kasser JR (2008). "Does swaddling influence developmental dysplasia of the hip?". Pediatrics. 121 (1): 177–8. doi:10.1542/peds.2007-1618. PMID 18166571. S2CID 37598276. 17. ^ "Baby Carriers, Seats, & Other Equipment - International Hip Dysplasia Institute". 18. ^ "Hip-Healthy Swaddling - International Hip Dysplasia Institute". 19. ^ Hashmi, Jamil; Basit, Sulman; Khoshhal, Khalid (August 2019). "Genetics of developmental dysplasia of the hip: Recent progress and future perspectives". Journal of Musculoskeletal Surgery and Research. 3 (3): 245. doi:10.4103/jmsr.jmsr_46_19. S2CID 199547368. 20. ^ "Causes of Developmental Dysplasia of the Hip - International Hip Dysplasia Institute". 21. ^ "Developmental Dislocation of the Hip - Wheeless' Textbook of Orthopaedics". 22. ^ "HipDysplasia - Newborn Nursery at LPCH - Stanford University School of Medicine". 23. ^ Kamath S, Bramley D (2005). "Is 'clicky hip' a risk factor in developmental dysplasia of the hip?". Scott Med J. 50 (2): 56–8. doi:10.1177/003693300505000205. PMID 15977515. S2CID 23000620. 24. ^ "Newborn Screening and Prevention - International Hip Dysplasia Institute". 25. ^ "Hip Clicks and Hip Dysplasia - International Hip Dysplasia Institute". 26. ^ "Physical Examination of Infants - International Hip Dysplasia Institute". 27. ^ French LM, Dietz FR; Dietz (July 1999). "Screening for developmental dysplasia of the hip". American Family Physician. 60 (1): 177–84, 187–8. PMID 10414637. 28. ^ "Asymmetry Symptoms of DDH". 29. ^ "Physician Newborn Screening and Prevention - International Hip Dysplasia Institute". 30. ^ "Harris Hip Score - Orthopaedic Scores". www.orthopaedicscore.com. 31. ^ Wylde V, Learmonth ID, Cavendish VJ (2005). "The Oxford hip score: the patient's perspective". Health Qual Life Outcomes. 3: 66. doi:10.1186/1477-7525-3-66. PMC 1283979. PMID 16259627. 32. ^ Aguilar CM, Neumayr LD, Eggleston BE, et al. (2005). "Clinical evaluation of avascular necrosis in patients with sickle cell disease: Children's Hospital Oakland Hip Evaluation Scale--a modification of the Harris Hip Score". Arch Phys Med Rehabil. 86 (7): 1369–75. doi:10.1016/j.apmr.2005.01.008. PMID 16003666. 33. ^ Betsy Miller, The Parents' Guide to Hip Dysplasia, p 19. 34. ^ Sutherland, Denise; West, Sophie (2011). A Guide for Adults with Hip Dysplasia. pp. 7, 21–23. ISBN 978-0-9872152-0-8. Archived from the original on 10 April 2013. Retrieved 2 April 2013. 35. ^ Skaggs, David L.; Storer, Stephen K. (15 October 2006). "Developmental Dysplasia of the Hip". American Family Physician. 74 (8): 1310–1316. PMID 17087424. 36. ^ "Dr. Rose's Peripheral Brain--DEVELOPMENTAL DYSPLASIA OF THE HIP". faculty.washington.edu. 37. ^ a b Dietz, Frederick R.; Speer, Linda (1 July 1999). "Screening for Developmental Dysplasia of the Hip". American Family Physician. 60 (1): 177–84, 187–8. PMID 10414637. 38. ^ "eMedicine - Developmental Dysplasia of the Hip : Article by James McCarthy, MD, FAAOS". 20 October 2019. Cite journal requires `\|journal=` (help) 39. ^ a b "ACR Appropriateness Criteria - Developmental Dysplasia of the Hip (DDH)–Child". American College of Radiology. Revised 2018 40. ^ "Ultrasound Detection of DDH - International Hip Dysplasia Institute". 41. ^ "X-Ray Screening for Developmental Dysplasia of the Hip - International Hip Dysplasia Institute". 42. ^ a b c d e Initially largely copied from: Ruiz Santiago, Fernando; Santiago Chinchilla, Alicia; Ansari, Afshin; Guzmán Álvarez, Luis; Castellano García, Maria del Mar; Martínez Martínez, Alberto; Tercedor Sánchez, Juan (2016). "Imaging of Hip Pain: From Radiography to Cross-Sectional Imaging Techniques". Radiology Research and Practice. 2016: 1–15. doi:10.1155/2016/6369237. ISSN 2090-1941. PMC 4738697. PMID 26885391. Attribution 4.0 International (CC BY 4.0) license 43. ^ "Pavlik Harness". 44. ^ Czubak J, Piontek T, Niciejewski K, Magnowski P, Majek M, Płończak M (2004). "Retrospective analysis of the non-surgical treatment of developmental dysplasia of the hip using Pavlik harness and Fredjka pillow: comparison of both methods". Ortop Traumatol Rehabil. 6 (1): 9–13. PMID 17676003. 45. ^ "Femoral Nerve Palsy".[permanent dead link] 46. ^ Nakamura J, Kamegaya M, Saisu T, Someya M, Koizumi W, Moriya H (2007). "Treatment for developmental dysplasia of the hip using the Pavlik harness: long-term results". J Bone Joint Surg Br. 89 (2): 230–5. doi:10.1302/0301-620X.89B2.18057. PMID 17322441. Archived from the original on 24 December 2012. 47. ^ "Hip Spica Cast for Developmental Dysplasia of the Hip". 48. ^ "Traction with DDH Treatment". 49. ^ Lau EM, Lin F, Lam D, Silman A, Croft P (1995). "Hip osteoarthritis and dysplasia in Chinese men". Ann. Rheum. Dis. 54 (12): 965–9. doi:10.1136/ard.54.12.965. PMC 1010061. PMID 8546528. 50. ^ Lievense AM, Bierma-Zeinstra SM, Verhagen AP, Verhaar JA, Koes BW (2004). "Influence of hip dysplasia on the development of osteoarthritis of the hip". Ann. Rheum. Dis. 63 (6): 621–6. doi:10.1136/ard.2003.009860. PMC 1755018. PMID 15140766. 51. ^ Sutherland, Denise; West, Sophie (2011). A Guide for Adults with Hip Dysplasia. pp. 56–59. ISBN 978-0-9872152-0-8. 52. ^ Bialik V, Bialik GM, Blazer S, Sujov P, Wiener F, Berant M (1999). "Developmental dysplasia of the hip: a new approach to incidence". Pediatrics. 103 (1): 93–9. doi:10.1542/peds.103.1.93. PMID 9917445. S2CID 1595498. 53. ^ Kokavec M, Bialik V (2007). "Developmental dysplasia of the hip. Prevention and real incidence". Bratisl Lek Listy. 108 (6): 251–4. PMID 17972535. 54. ^ Developmental Dysplasia of the Hip at eMedicine 55. ^ "UNSW Embryology- Musculoskeletal System - Abnormalities". Archived from the original on 9 April 2008. Retrieved 19 April 2008. 56. ^ "ER - Out on a Limb (2006)". Retrieved 31 August 2012. 57. ^ Workingdogs.com. "Canine hip dysplasia". Workingdogs.com. Retrieved 18 August 2013. 58. ^ Ettinger, Stephen J.; Feldman, Edward C. (1995). Textbook of Veterinary Internal Medicine (4th ed.). W. B. Saunders Company. ISBN 0-7216-6795-3. ## External links[edit] * Online orthopedic textbook Classification D * ICD-10: Q65 * ICD-9-CM: 754.3 * OMIM: 142700 * MeSH: D006618 * DiseasesDB: 3056 External resources * MedlinePlus: 000971 * eMedicine: orthoped/456 * v * t * e Congenital malformations and deformations of musculoskeletal system / musculoskeletal abnormality Appendicular limb / dysmelia Arms clavicle / shoulder * Cleidocranial dysostosis * Sprengel's deformity * Wallis–Zieff–Goldblatt syndrome hand deformity * Madelung's deformity * Clinodactyly * Oligodactyly * Polydactyly Leg hip * Hip dislocation / Hip dysplasia * Upington disease * Coxa valga * Coxa vara knee * Genu valgum * Genu varum * Genu recurvatum * Discoid meniscus * Congenital patellar dislocation * Congenital knee dislocation foot deformity * varus * Club foot * Pigeon toe * valgus * Flat feet * Pes cavus * Rocker bottom foot * Hammer toe Either / both fingers and toes * Polydactyly / Syndactyly * Webbed toes * Arachnodactyly * Cenani–Lenz syndactylism * Ectrodactyly * Brachydactyly * Stub thumb reduction deficits / limb * Acheiropodia * Ectromelia * Phocomelia * Amelia * Hemimelia multiple joints * Arthrogryposis * Larsen syndrome * RAPADILINO syndrome Axial Skull and face Craniosynostosis * Scaphocephaly * Oxycephaly * Trigonocephaly Craniofacial dysostosis * Crouzon syndrome * Hypertelorism * Hallermann–Streiff syndrome * Treacher Collins syndrome other * Macrocephaly * Platybasia * Craniodiaphyseal dysplasia * Dolichocephaly * Greig cephalopolysyndactyly syndrome * Plagiocephaly * Saddle nose Vertebral column * Spinal curvature * Scoliosis * Klippel–Feil syndrome * Spondylolisthesis * Spina bifida occulta * Sacralization Thoracic skeleton ribs: * Cervical * Bifid sternum: * Pectus excavatum * Pectus carinatum [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Hip dysplasia	c1306065	28,589	wikipedia	https://en.wikipedia.org/wiki/Hip_dysplasia	2021-01-18T18:46:13	{"gard": ["6659"], "mesh": ["D006618"], "umls": ["C1306065", "C0019555"], "icd-9": ["754.3"], "icd-10": ["Q65"], "wikidata": ["Q625935"]}
For a phenotypic description and a discussion of genetic heterogeneity of benign familial neonatal seizures, see BFNS1 (121200). Clinical Features Concolino et al. (2002) reported a family in which 3 members over 3 generations had benign neonatal seizures inherited in an autosomal dominant pattern. Cytogenetics By cytogenic analysis in a family with benign neonatal seizures, Concolino et al. (2002) identified a pericentric inversion of chromosome 5, inv(5)(p15q11), which was present in all 3 affected members and absent in 3 unaffected first-degree relatives. The authors noted that the breakpoint was different from that found in cri-du-chat syndrome (123450). INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Seizures, generalized tonic-clonic MISCELLANEOUS \- Onset in first months of life \- Seizures usually remit spontaneously by 12 months of age \- No neurologic sequelae ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	SEIZURES, BENIGN FAMILIAL NEONATAL, 3	c0220669	28,590	omim	https://www.omim.org/entry/608217	2019-09-22T16:08:09	{"mesh": ["D020936"], "omim": ["608217"], "orphanet": ["1949"], "synonyms": ["Alternative titles", "CONVULSIONS, BENIGN FAMILIAL NEONATAL, 3"]}
A number sign (#) is used with this entry because Bainbridge-Ropers syndrome (BRPS) is caused by heterozygous mutation in the ASXL3 gene (615115) on chromosome 18q12. Description Bainbridge-Ropers syndrome (BRPS) is a developmental disorder characterized by delayed psychomotor development, severe intellectual disability with poor or absent speech, hypotonia, feeding difficulties, poor growth, and dysmorphic facial features (summary by Srivastava et al., 2016). Clinical Features Bainbridge et al. (2013) reported 4 individuals from 4 unrelated families with phenotypic features similar to those of Bohring-Opitz syndrome (605039) but with no specific recognizable syndromic diagnosis. Three of the subjects had similar clinical histories, including severe psychomotor retardation, feeding problems, severe postnatal growth retardation, arched eyebrows, anteverted nares, and ulnar deviation of the hands. The fourth subject also had anteverted nares but had less severe psychomotor retardation and normal growth. No patient had the typical 'BOS posture' of elbow and wrist flexion, or of myopia or trigonocephaly. Only 1 subject had brain MRI, which showed global mild white matter volume loss, secondary brainstem hypoplasia, and bilateral hypoplasia/dysplasia of cerebellar tonsils. MR spectroscopy was normal. Srivastava et al. (2016) reported 3 unrelated patients with BRPS. All had feeding difficulties necessitating a feeding tube, failure to thrive, hypotonia, and developmental delay with absent speech and poor or absent independent walking. They had variable dysmorphic features, including arched eyebrows, downslanting palpebral fissures, broad nasal bridge with short nose and anteverted nares, low-set ears, and small chin. Brain imaging, performed in 2 patients, showed loss of white matter; 1 patient had a thin corpus callosum. Balasubramanian et al. (2017) reported 12 unrelated patients with BRPS confirmed by genetic analysis. The patients, who ranged in age from 4 to 22 years, were ascertained from the Deciphering Developmental Disorders (DDD) project. Most patients presented in early infancy with feeding difficulties, poor overall growth, relative microcephaly, and hypotonia. All had delayed psychomotor development with moderate to profound intellectual disability and delayed walking. Two patients were nonambulatory and 9 were nonverbal. Most also had autistic features and 11 were in a special needs school. Three patients had controlled seizures and several had sleep problems. The patients had common, if variable, dysmorphic features, including prominent forehead, narrow head, hypertelorism, down- or upslanting palpebral fissures, strabismus, high-arched eyebrows, long tubular nose, prominent nasal bridge, broad or bulbous nasal tip, low columella, open mouth with everted lower lip, high-arched palate, and crowded teeth. Three patients had a marfanoid habitus with arachnodactyly, tall stature, pes planus, and scoliosis. A few patients had nonspecific minor abnormalities on brain imaging. Molecular Genetics Using whole-exome and whole-genome sequencing, Bainbridge et al. (2013) identified different de novo nonsense and frameshift mutations in the ASXL3 gene in each of the 4 patients (615115.0001-615115.0004). In 3 unrelated patients with BRPS, Srivastava et al. (2016) identified 3 de novo heterozygous frameshift or nonsense mutations in the ASXL1 gene (615115.0005-615115.0007). Fibroblasts derived from 1 of the patients with a frameshift mutation in the 5-prime cluster region (c.1448dupT; 615115.0005) showed about a 50% decrease in ASXL1 mRNA and protein levels, consistent with haploinsufficiency. These cells showed significantly increased levels of H2AK119Ub1, indicating that this mutation disrupts the normal activity of the polycomb repressive deubiquitination (PR-DUB) complex, which functions to remove the monoubiquitin from lysine-119 of histone H2A (H2AK119Ub1), thus playing a role in chromatin remodeling and transcriptional regulation. Transcriptome analysis of these cells showed dysregulation of many genes, including those involved in transcriptional regulation, development, and proliferation, as well as in digestive tract development. These findings highlighted a role for dynamic regulation of H2A ubiquitination in development and disease. In 12 unrelated patients with BRPS, Balasubramanian et al. (2017) identified 12 different de novo heterozygous nonsense or frameshift mutations in the ASXL3 gene (see, e.g., 615115.0006 and 615115.0008). The patients were ascertained from the Deciphering Developmental Disorders (DDD) project, and the mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. Functional studies of the variants and studies of patient cells were not performed, but all were predicted to result in a loss of function. The authors noted that the mutations reported by Bainbridge et al. (2013) clustered mainly within the 5-prime end of exon 11 between codons 404 and 659. This region lies between the N-terminal protein scaffolding functional domains of the gene and the C-terminal chromatin/DNA-targeting functional domain. Among their cohort, Balasubramanian et al. (2017) noted that 5 of the identified mutations occurred within the original cluster region, whereas 7 occurred 3-prime to this region, suggesting a second cluster region between codons 1045 and 1444. There were no phenotypic differences between patients with mutations in the different cluster regions. INHERITANCE \- Autosomal dominant GROWTH Other \- Failure to thrive \- Poor overall growth \- Marfanoid habitus (in some patients) HEAD & NECK Head \- Microcephaly \- Narrow head Face \- Prominent forehead Eyes \- Hypertelorism \- Downslanting palpebral fissures \- Upslanting palpebral fissures \- Strabismus \- Arched eyebrows Nose \- Prominent nasal bridge \- Long tubular nose \- Broad nasal tip \- Low columella \- Short nose \- Anteverted nares Mouth \- Wide mouth \- Everted lower lip \- High-arched palate Teeth \- Crowded teeth ABDOMEN Gastrointestinal \- Feeding difficulties SKELETAL Spine \- Scoliosis (in some patients) Hands \- Arachnodactyly (in some patients) Feet \- Pes planus (in some patients) MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Intellectual disability, severe to profound \- Poor or absent speech \- Delayed walking \- Inability to walk \- Seizures (rare) \- Nonspecific white matter abnormalities on brain imaging \- Thin corpus callosum Behavioral Psychiatric Manifestations \- Autistic features \- Hand-flapping MISCELLANEOUS \- Onset in early infancy \- De novo mutation MOLECULAR BASIS \- Caused by mutation in the additional sex combs-like 3 gene (ASXL3, 615115.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	BAINBRIDGE-ROPERS SYNDROME	c3809650	28,591	omim	https://www.omim.org/entry/615485	2019-09-22T15:51:56	{"omim": ["615485"], "orphanet": ["352577"], "synonyms": ["Bainbridge-Roppers syndrome"]}
A number sign (#) is used with this entry because of evidence that brain small vessel disease-2 (BSVD2) is caused by heterozygous mutation in the COL4A2 gene (120090) on chromosome 13q34. Description Brain small vessel disease-2 is an autosomal dominant disorder characterized by variable neurologic impairment resulting from disturbed vascular supply that leads to cerebral degeneration. The disorder is often associated with 'porencephaly' on brain imaging. Affected individuals typically have hemiplegia, seizures, and intellectual disability, although the severity is variable (summary by Yoneda et al., 2012). For a discussion of genetic heterogeneity of brain small vessel disease, see BSVD1 (175780). Clinical Features Yoneda et al. (2012) reported a Japanese family with autosomal dominant inheritance of brain small vessel disease associated with porencephaly of varying severity. The proband was found to have an enlarged right lateral ventricle at age 31 weeks' gestation. He showed delayed early development, particularly of motor skills, with poor left hand use, abnormal leg movement, and delayed walking. At age 3, he showed spastic triplegia with left hemiplegic and diplegic gait. He developed seizures at age 10 months, and EEG showed focal spikes in the right frontal region, with later involvement of the right occipital to posterior temporal region and midcentral region. Brain MRI at age 6 years showed an enlarged right lateral ventricle, reduced volume of the right frontal white matter, and atrophic right cerebral peduncle and body of corpus callosum. IQ was 74. His mother had focal seizures at age 18 months, which were well-controlled. She had clumsiness of the left hand in later childhood, as well as transient headaches. At age 31 years, she had very mild monoparesis of the left upper extremity. Brain MRI showed a mildly enlarged right lateral ventricle, and evidence of mild porencephaly or periventricular venous infarction around the enlarged ventricular wall on FLAIR imaging. The proband's maternal uncle and maternal granduncle also had a history of congenital hemiplegia, suggesting a genetic predisposition in the family. A second unrelated Japanese proband was severely affected. He had low APGAR scores and mild asphyxia at birth. Brain ultrasound showed a parenchymal hemorrhage of the right cerebral hemisphere with an enlarged left lateral ventricle. He also showed a coagulation defect, with increased PT and APTT, and received fresh frozen plasma. The coagulation defect normalized at age 7 months. At age 37 days, he had a ventricular shunt placed for progressive enlargement of the lateral ventricles. CT scan at age 2 months showed extremely reduced white matter in the frontal lobes. At age 1 year, 4 months, he had spastic quadriplegia and very poor development. An elder sister had an intraventricular hemorrhage 2 days after birth and underwent ventriculoperitoneal shunting. Her development was almost normal, although internal strabismus was noted. However, she died in an accident at the age of 4 years, and DNA was unavailable. Cavallin et al. (2018) reported 2 unrelated children, 4 and 11 years of age, with BSVD2. The patients were ascertained from a cohort of patients with cortical malformations. Both had small head circumference (-2 SD), and severe global developmental delay with no language and spastic tetraplegia; 1 had poor overall growth and a feeding tube. One had onset of refractory seizures at 5 months of age; the other had controlled focal seizures. Ophthalmologic examination showed normal fundus in both children, but 1 had intermittent eye fixation and small/tilted optic discs, and the other had esotropia. Brain imaging showed various abnormalities in both patients, including schizencephaly, polymicrogyria, pachygyria, and subcortical and subependymal nodular heterotopia. There were no signs of previous hemorrhage or calcifications. Zagaglia et al. (2018) reviewed the epileptic seizure phenotype among patients with COL4A2 mutations, noting that most patients have focal onset associated with localization of porencephaly. Inheritance The transmission pattern of BSVD2 in the family reported by Yoneda et al. (2012) indicated autosomal dominant inheritance with incomplete penetrance, as 1 carrier was unaffected. Molecular Genetics In affected members of a family with BSVD2, Yoneda et al. (2012) identified a heterozygous mutation in the COL4A2 gene (G1152D; 120090.0001). A second heterozygous de novo mutation (G1037E; 120090.0002) was found in an unrelated Japanese boy with the disorder. Overall, these mutations were found in 2 of 35 Japanese patients with porencephaly on brain imaging. COL4A2 was selected as a candidate for sequencing because COL4A1 (120130), with which it forms a heterotrimer, causes BSVD1. In 2 unrelated patients with BSVD2, Cavallin et al. (2018) identified heterozygous mutations in the COL4A2 gene (G1377R, 120090.0006 and c.1776+1G-A, 120090.0007). The mutations, which were found by direct analysis of the COL4A2 gene and confirmed by Sanger sequencing, were filtered against public databases. Both mutations were inherited from the mothers. The mother of patient 2 was unaffected, whereas the mother of patient 1 had periventricular white matter hypersignals, but had no neurologic symptoms. Family history of this family revealed that a previous pregnancy of the mother had been interrupted due to fetal cerebral hemorrhage; DNA analysis of the fetus found the mutation. In addition, the maternal grandfather of the proband had died of cerebral hemorrhage at age 40 years; DNA was not available from him. Functional studies of the variants and studies of patient cells were not performed, but the mutations were classified as pathogenic based on ACMG criteria. INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Porencephaly \- Enlarged ventricles \- Intracranial hemorrhage \- Hemiplegia \- Spasticity \- Delayed psychomotor development \- Poor or absent speech \- Seizures \- Reduced white matter volume \- Structural brain anomalies Schizencephaly \- Polymicrogyria \- Pachygyria \- Nodular heterotopia MISCELLANEOUS \- Variable severity \- Incomplete penetrance MOLECULAR BASIS \- Caused by mutation in the type IV collagen alpha-2 gene (COL4A2, 120090.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	BRAIN SMALL VESSEL DISEASE 2	c1867983	28,592	omim	https://www.omim.org/entry/614483	2019-09-22T15:55:08	{"doid": ["0060263"], "mesh": ["D065708"], "omim": ["614483"], "orphanet": ["99810", "2940"], "synonyms": ["Alternative titles", "PORENCEPHALY 2, FORMERLY"]}
Abnormal fear of thunder and lightning Astraphobia Other namesBrontophobia Lightning strikes during a storm SpecialtyPsychology Astraphobia, also known as astrapophobia, brontophobia, keraunophobia, or tonitrophobia is an abnormal fear of thunder and lightning or an unwarranted fear of scattered and/or isolated thunderstorms, a type of specific phobia. It is a treatable phobia that both humans and animals can develop. The term astraphobia is composed of the Greek words ἀστραπή (astrape; lightning) and φόβος (phobos; fear). ## Contents * 1 Signs and symptoms * 2 Children * 3 Treatment * 4 Dogs and cats * 5 See also * 6 References ## Signs and symptoms[edit] A person with astraphobia will often feel anxious during a thunderstorm even when they understand that the threat to them is minimal. Some symptoms are those accompanied with many phobias, such as trembling, crying, sweating, panicked reactions, the sudden feeling of using the bathroom, nausea, the feeling of dread, insertion of the fingers in the ears, and rapid heartbeat. However, there are some reactions that are unique to astraphobia. For instance, reassurance from other people is usually sought, and symptoms worsen when alone. Many people who have astraphobia will look for extra shelter from the storm.[1] They might hide underneath a bed, under the covers, in a closet, in a basement, or any other space where they feel safer. Efforts are usually made to smother the sound of the thunder; the person may cover their ears or curtain the windows. A typical sign that someone has astraphobia is a very heightened interest in weather forecasts. An astraphobic person will be alert for news of incoming storms. They may watch the weather on television constantly during rainy bouts and may even track thunderstorms online. This can become severe enough that the person may not go outside without checking the weather first. This can lead to anxiety. In very extreme cases, astraphobia can lead to agoraphobia, the fear of leaving the home. ## Children[edit] In 2007 scientists found astraphobia is the third most prevalent phobia in the US.[2] It can occur in people of any age. It occurs in many children, and should not be immediately identified as a phobia because children naturally go through many fears as they mature. Their fear of thunder and lightning cannot be considered a fully developed phobia unless it persists for more than six months. In this case, the child's phobia should be addressed, for it may become a serious problem in adulthood. To lessen a child's fear during thunderstorms, the child can be distracted by games and activities. A bolder approach is to treat the storm as an entertainment; a fearless adult is an excellent role model for children. ## Treatment[edit] The most widely used and possibly the most effective treatment for astraphobia is exposure to thunderstorms and eventually building an immunity. Some other treatment methods include Cognitive behavioral therapy [3] (CBT) and Dialectical behavioral therapy (DBT). The patient will in many cases be instructed to repeat phrases to himself or herself in order to become calm during a storm. Heavy breathing exercises can reinforce this effort. ## Dogs and cats[edit] Dogs may exhibit severe anxiety during thunderstorms; between 15 and 30 percent may be affected.[4] Research confirms high levels of cortisol \- a hormone associated with stress - affects dogs during and after thunderstorms.[4] Remedies include behavioral therapies such as counter conditioning and desensitization, anti-anxiety medications, and dog appeasing pheromone, a synthetic analogue of a hormone secreted by nursing canine mothers.[5] Studies have also shown that cats can be afraid of thunderstorms. Whilst it is less common, cats have been known to hide under a table or behind a couch during a thunderstorm.[6] Generally if any animal is anxious during a thunderstorm or any similar, practically harmless event (e.g. fireworks display), it is advised to simply continue behaving normally, instead of attempting to comfort animals. Showing fearlessness is, arguably, the best method to "cure" the anxiety. ## See also[edit] * Lilapsophobia * List of phobias ## References[edit] 1. ^ Johnson, Trevor "Fear of Thunder - Dealing With Astraphobia." Fear of Thunder- Dealing with Astraphobia. 30 Jan. 2009. EzineArticles.com. 14 Oct 2009 2. ^ Dennis Coon, John O. Mitterer (2008). Introduction to Psychology: Gateways to Mind and Behavior. Cengage Publishing. p. 482. ISBN 978-0-495-59911-1. 3. ^ Fritscher, Lisa Astraphobia - Fear of Thunder and Lightning. 30 Apr. 2011. About.com. Retrieved on 30 June 2014. 4. ^ a b "Research aimed at finding way to soothe thunderstorm-stressed doggos". Pennsylvania State University. Archived from the original on 2012-12-14. Retrieved 2010-05-21. 5. ^ "There's Hope for Thunder-Phobic Dogs". University of Illinois. Retrieved 2010-05-23. 6. ^ Cato (2010-08-03). "Thunderstorms Phobia in Cats – Cats and Thunderstorms". Our-cats.com. Retrieved 2011-10-26. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Astraphobia	c0522190	28,593	wikipedia	https://en.wikipedia.org/wiki/Astraphobia	2021-01-18T18:29:16	{"wikidata": ["Q2000742"]}
A rare neurologic disease characterized by recurrent mononeuropathies usually triggered by minor physical activities innocuous to healthy people. ## Epidemiology Hereditary neuropathy with liability to pressure palsies (HNPP) actual prevalence is unknown due to under-diagnosis but estimates range between 1/50,000 -1/20,000 worldwide. In Finland, the prevalence is reported to be 1/6250. ## Clinical description Disease onset usually occurs in the 2nd to 3rd decade of life, but may present in childhood. Some patients are asymptomatic and never diagnosed. The most common presenting symptom is the sudden onset of focal sensory loss and muscle weakness in the distribution of a single nerve. In many cases, these acute focal symptoms are triggered by mechanical stresses to the nerve, such as compression, repetitive movement or stretching of the affected limbs. Commonly affected nerves include the peroneal nerve at the fibular head, ulnar nerve at the elbow, median nerve at the wrist, brachial plexus and radial nerve. Clinical manifestations caused by these mononeuropathies include foot drop, hand numbness and weakness, arm weakness, and sensory loss over the index finger and thumb or lateral aspect of the hand. In 50% of cases, patients recover from these episodes within a few days to months but others have incomplete recovery and suffer from recurrent focal sensory and motor deficits. In rare cases, brachial plexopathy with unilateral painless arm paralysis and sensory loss may be a presenting symptom. Occasionally, mild impairments of cranial nerve functions may be seen. Absent deep tendon reflexes and pes cavus foot deformity are seen in some patients but not in others. The phenotype of HNPP often evolves into a symmetric sensory motor polyneuropathy in aged patients. Many patients with HNPP complain of diffuse pain and severe fatigue. HNPP may cause severe limb paralysis when asymptomatic patients with unknown diagnosis of HNPP are challenged by strenuous physical activities. This imposes a catastrophic risk in a fraction of patients with HNPP. ## Etiology HNPP is due to a mutation in the chromosome 17p12 containing PMP22 and other genes. PMP22 encodes the peripheral myelin protein-22 (PMP22) that is predominantly expressed in the compact myelin of the peripheral nervous system. In 80% of cases, a 1.4Mb deletion at 17p11.2 that includes the PMP22 gene is found, and in the remaining 20%, patients may carry a point mutation or small deletion in PMP22 or mutations in as yet unidentified genes. ## Diagnostic methods Diagnosis of HNPP is typically suggested by the presence of recurrent focal mononeuropathies and the evidence of a family history. Electrophysiologic testing shows prolonged distal latency at the sites susceptible to mechanical stress. Conduction velocities out of these sites are often either normal or only mildly slowed. Tomacula (focal thickening of the myelin sheath) is the characteristic histological finding in sural nerve biopsies. It may however be seen in other types of neuropathies. A DNA test showing the PMP22 heterozygous deletion confirms the diagnosis. ## Differential diagnosis Differential diagnosis includes both compression induced mononeuropathies and generalized polyneuropathies. HNPP can sometimes be mistaken for neuralgic amyotrophy, stroke or multiple sclerosis. ## Antenatal diagnosis Prenatal testing is theoretically possible in families where the disease causing gene has been identified. ## Genetic counseling The disorder is inherited autosomal dominantly. Genetic counseling should be done for individuals having the disease and informing them that there is 50% risk of passing the mutation to offspring. ## Management and treatment Consultation should be provided to the patient about physical activities that may trigger the sensory/motor deficits. Those with foot drop or wrist drop may benefit from an ankle-foot orthosis or a wrist splint. Protective pads for the elbows and knees can alleviate nerves from mechanical stresses. Activities that involve prolonged sitting with crossed legs, leaning on elbows and repetitive movements of the wrists, as well as rapid weight loss should be avoided. Vincristine should equally be avoided. Cautions should be taken when new medications are prescribed with potential side-effect to the peripheral nerves. ## Prognosis HNPP is not life threatening and does not appear to affect longevity. However, many patients may have incomplete recovery in their sensory moto deficits. In some cases, severe and prolonged limb paralysis can occur, particularly after strenuous physical activities. Many patients with HNPP suffer from pain and fatigue. Unfortunately, these issues have not been well studied and should be addressed in future investigations. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Hereditary neuropathy with liability to pressure palsies	c0393814	28,594	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=640	2021-01-23T17:53:07	{"gard": ["5221"], "mesh": ["C536965"], "omim": ["162500"], "umls": ["C0393814"], "icd-10": ["G60.0"], "synonyms": ["Current pressure-sensitive neuropathy", "HNPP", "Heterozygous microdeletion 17p11.2p12", "Potato-grubbing palsy", "Tomaculous neuropathy", "Tulip-bulb digger's palsy"]}
Abortion in Botswana is only legal if the abortion will save the woman's life, if the pregnancy gravely endangers the woman's physical or mental health, or if it is a result of rape or incest.[1] In Botswana, abortions that meet these requirements must be performed within the first 16 weeks of pregnancy in a government hospital and must be approved by two physicians.[1] ## Impact of restrictive abortion laws[edit] Though women in Botswana are recognized as having some of the best access to abortions in Sub-Saharan Africa because of these exceptions, many women are still resorting to unsafe abortions and self-induced abortions, commonly leading to maternal death.[1] ## Socio-cultural impacts on abortion[edit] In Botswana, many families still follow the lobolo custom where men pay a woman's family in order to take her as a bride.[2] This has established an expectation that husbands have paid for and own their wives' bodies, including their reproductive rights.[2] Even though this sentiment may lead to pregnancy that is a result of rape, hospitals and clinics are unlikely to approve marital rape cases as justifying abortion, as cultural norms suggest husbands are entitled to their wives' bodies.[2] ## References[edit] 1. ^ a b c Abortion Policies: Afghanistan to France. United Nations Publications. 2001. Retrieved 4 December 2014. 2. ^ a b c Smith, Stephanie S. (Dec 2013). "Reproductive health and the question of abortion in Botswana: a review". African Journal of Reproductive Health. 17 (4). Retrieved 4 December 2014. * v * t * e Abortion in Africa Sovereign states * Algeria * Angola * Benin * Botswana * Burkina Faso * Burundi * Cameroon * Cape Verde (Cabo Verde) * Central African Republic * Chad * Comoros * Democratic Republic of the Congo * Republic of the Congo * Djibouti * Egypt * Equatorial Guinea * Eritrea * Eswatini (Swaziland) * Ethiopia * Gabon * The Gambia * Ghana * Guinea * Guinea-Bissau * Ivory Coast (Côte d'Ivoire) * Kenya * Lesotho * Liberia * Libya * Madagascar * Malawi * Mali * Mauritania * Mauritius * Morocco * Mozambique * Namibia * Niger * Nigeria * Rwanda * São Tomé and Príncipe * Senegal * Seychelles * Sierra Leone * Somalia * South Africa * South Sudan * Sudan * Tanzania * Togo * Tunisia * Uganda * Zambia * Zimbabwe States with limited recognition * Sahrawi Arab Democratic Republic * Somaliland Dependencies and other territories * Canary Islands / Ceuta / Melilla (Spain) * Madeira (Portugal) * Mayotte / Réunion (France) * Saint Helena / Ascension Island / Tristan da Cunha (United Kingdom) * 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 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Abortion in Botswana	None	28,595	wikipedia	https://en.wikipedia.org/wiki/Abortion_in_Botswana	2021-01-18T18:52:43	{"wikidata": ["Q19568850"]}
A very rare multiple congenital anomaly syndrome characterized by the presence of anophthalmia or severe microphthalmia, cleft lip/palate, facial cleft and sacral neural tube defects, along with various additional anomalies including congenital glaucoma, iris coloboma, primary hyperplastic vitreous, hypertelorism, low-set ears, clinodactyly, choanal atresia/stenosis, dysgenesis of sacrum, tethering of spinal cord, syringomyelia, hypoplasia of corpus callosum, cerebral ventriculomegaly and endocrine abnormalities. An autosomal recessive inheritance has been suggested. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Anophthalmia plus syndrome	c1833339	28,596	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1104	2021-01-23T18:00:40	{"gard": ["719"], "mesh": ["C537767"], "omim": ["600776"], "umls": ["C1833339"], "icd-10": ["Q87.8"], "synonyms": ["Fryns microphthalmia syndrome", "Microphthalmia with facial clefting"]}
Ascending cholangitis Other namesacute cholangitis, cholangitis Duodenoscopy image of pus extruding from Ampulla of Vater, indicative of cholangitis SpecialtyGastroenterology Symptomsjaundice, fever and abdominal pain Ascending cholangitis, also known as acute cholangitis or simply cholangitis, is inflammation of the bile duct (cholangitis), usually caused by bacteria ascending from its junction with the duodenum (first part of the small intestine). It tends to occur if the bile duct is already partially obstructed by gallstones.[1][2] Cholangitis can be life-threatening, and is regarded as a medical emergency.[1] Characteristic symptoms include yellow discoloration of the skin or whites of the eyes, fever, abdominal pain, and in severe cases, low blood pressure and confusion. Initial treatment is with intravenous fluids and antibiotics, but there is often an underlying problem (such as gallstones or narrowing in the bile duct) for which further tests and treatments may be necessary, usually in the form of endoscopy to relieve obstruction of the bile duct.[1][3] The word is from Greek chol-, bile + ang-, vessel + -itis, inflammation. ## Contents * 1 Signs and symptoms * 2 Causes * 3 Pathogenesis * 4 Diagnosis * 4.1 Blood tests * 4.2 Medical imaging * 5 Treatment * 5.1 Fluids and antibiotics * 5.2 Endoscopy * 5.3 Percutaneous biliary drainage * 5.4 Cholecystectomy * 6 Prognosis * 7 Epidemiology * 8 History * 9 See also * 10 References * 11 External links ## Signs and symptoms[edit] Charcot's triad A person with cholangitis may complain of abdominal pain (particularly in the right upper quadrant of the abdomen), fever, rigors (uncontrollable shaking) and a feeling of uneasiness (malaise). Some may report jaundice (yellow discoloration of the skin and the whites of the eyes).[1] Physical examination findings typically include jaundice and right upper quadrant tenderness.[1] Charcot's triad is a set of three common findings in cholangitis: abdominal pain, jaundice, and fever.[4] This was assumed in the past to be present in 50–70% of cases, although more recently the frequency has been reported as 15–20%.[1] Reynolds' pentad includes the findings of Charcot's triad with the presence of septic shock and mental confusion.[5] This combination of symptoms indicates worsening of the condition and the development of sepsis, and is seen less commonly still.[1][2] In the elderly, the presentation may be atypical; they may directly collapse due to sepsis without first showing typical features.[2] Those with an indwelling stent in the bile duct (see below) may not develop jaundice.[2] ## Causes[edit] Bile duct obstruction, which is usually present in acute cholangitis, is generally due to gallstones. 10–30% of cases, however, are due to other causes such as benign stricturing (narrowing of the bile duct without an underlying tumor), postoperative damage or an altered structure of the bile ducts such as narrowing at the site of an anastomosis (surgical connection), various tumors (cancer of the bile duct, gallbladder cancer, cancer of the ampulla of Vater, pancreatic cancer, cancer of the duodenum), anaerobic organisms such as Clostridium and Bacteroides (especially in the elderly and those who have undergone previous surgery of the biliary system).[1] Parasites which may infect the liver and bile ducts may cause cholangitis; these include the roundworm Ascaris lumbricoides and the liver flukes Clonorchis sinensis, Opisthorchis viverrini and Opisthorchis felineus.[6] In people with AIDS, a large number of opportunistic organisms has been known to cause AIDS cholangiopathy, but the risk has rapidly diminished since the introduction of effective AIDS treatment.[1][7] Cholangitis may also complicate medical procedures involving the bile duct, especially ERCP. To prevent this, it is recommended that those undergoing ERCP for any indication receive prophylactic (preventative) antibiotics.[3][8] The presence of a permanent biliary stent (e.g. in pancreatic cancer) slightly increases the risk of cholangitis, but stents of this type are often needed to keep the bile duct patent under outside pressure.[1] ## Pathogenesis[edit] Diagram showing liver and related parts of the digestive system Bile is produced by the liver, and serves to eliminate cholesterol and bilirubin from the body, as well as emulsifying of fats to make them more soluble in water and aid in their digestion. Bile is formed in the liver by hepatocytes (liver cells) and excreted into the common hepatic duct. Part of the bile is stored in the gall bladder because of back pressure (exerted by the sphincter of Oddi), and may be released at the time of digestion. The gallbladder also concentrates the bile by absorbing water and dissolved salts from it. All bile reaches the duodenum (first part of the small intestine) through the common bile duct and the ampulla of Vater. The sphincter of Oddi, located at the junction of the ampulla of Vater and the duodenum, is a circular muscle that controls the release of both bile and pancreatic secretions into the digestive tract.[1] The biliary tree is normally relatively free of bacteria because of certain protective mechanisms. The sphincter of Oddi acts as a mechanical barrier. The biliary system normally has low pressure (8 to 12 cmH2O)[9] and allows bile to flow freely through. The continuous forward flow of the bile in the duct flushes bacteria, if present, into the duodenum, and does not allow the establishment of an infection. The constitution of bile—bile salts[1] and immunoglobulin[2] secreted by the epithelium of the bile duct also has a protective role. Bacterial contamination alone in absence of obstruction does not usually result in cholangitis.[2] However increased pressure within the biliary system (above 20 cmH2O)[10] resulting from obstruction in the bile duct widens spaces between the cells lining the duct, bringing bacterially contaminated bile in contact with the blood stream. It also adversely affects the function of Kupffer cells, which are specialized macrophage cells that assist in preventing bacteria from entering the biliary system. Finally, increased biliary pressure decreases production of IgA immunoglobulins in the bile.[11] This results in bacteremia (bacteria in the blood stream) and gives rise to the systemic inflammatory response syndrome (SIRS) comprising fever (often with rigors), tachycardia, increased respiratory rate and increased white blood cell count; SIRS in the presence of suspected or confirmed infection is called sepsis.[1] Biliary obstruction itself disadvantages the immune system and impairs its capability to fight infection, by impairing the function of certain immune system cells (neutrophil granulocytes) and modifying the levels of immune hormones (cytokines).[1] In ascending cholangitis, it is assumed that organisms migrate backwards up the bile duct as a result of partial obstruction and decreased function of the sphincter of Oddi.[1] Other theories about the origin of the bacteria, such as through the portal vein or transmigration from the colon, are considered less likely.[1] ## Diagnosis[edit] ### Blood tests[edit] Routine blood tests show features of acute inflammation (raised white blood cell count and elevated C-reactive protein level), and usually abnormal liver function tests (LFTs). In most cases the LFTs will be consistent with obstruction: raised bilirubin, alkaline phosphatase and γ-glutamyl transpeptidase. In the early stages, however, pressure on the liver cells may be the main feature and the tests will resemble those in hepatitis, with elevations in alanine transaminase and aspartate transaminase.[1] Blood cultures are often performed in people with fever and evidence of acute infection. These yield the bacteria causing the infection in 36% of cases,[12] usually after 24–48 hours of incubation. Bile, too, may be sent for culture during ERCP (see below). The most common bacteria linked to ascending cholangitis are gram-negative bacilli: Escherichia coli (25–50%), Klebsiella (15–20%) and Enterobacter (5–10%). Of the gram-positive cocci, Enterococcus causes 10–20%.[13] ### Medical imaging[edit] Cholangiogram through a nasobiliary drain showing the common bile duct in black (diagonally from top left to bottom right in the center) with an interruption in the contour due to a large gallstone. Given that ascending cholangitis usually occurs in the setting of bile duct obstruction, various forms of medical imaging may be employed to identify the site and nature of this obstruction. The first investigation is usually ultrasound, as this is the most easily available.[1] Ultrasound may show dilation of the bile duct and identifies 38% of bile duct stones; it is relatively poor at identifying stones farther down the bile duct. Ultrasound can help distinguish between cholangitis and cholecystitis (inflammation of the gallbladder), which has similar symptoms to cholangitis but appears differently on ultrasound.[14] A better test is magnetic resonance cholangiopancreatography (MRCP), which uses magnetic resonance imaging (MRI); this has a comparable sensitivity to ERCP.[14] Smaller stones, however, can still be missed on MRCP depending on the quality of the hospital's facilities.[1] The gold standard test for biliary obstruction is still endoscopic retrograde cholangiopancreatography (ERCP). This involves the use of endoscopy (passing a tube through the mouth into the esophagus, stomach and thence to the duodenum) to pass a small cannula into the bile duct. At that point, radiocontrast is injected to opacify the duct, and X-rays are taken to get a visual impression of the biliary system. On the endoscopic image of the ampulla, one can sometimes see a protuberant ampulla from an impacted gallstone in the common bile duct or the frank extrusion of pus from the common bile duct orifice. On the X-ray images (known as cholangiograms), gallstones are visible as non-opacified areas in the contour of the duct. For diagnostic purposes, ERCP has now generally been replaced by MRCP. ERCP is only used first-line in critically ill patients in whom delay for diagnostic tests is not acceptable; however, if the index of suspicion for cholangitis is high, an ERCP is typically done to achieve drainage of the obstructed common bile duct.[1] If other causes rather than gallstones are suspected (such as a tumor), computed tomography and endoscopic ultrasound (EUS) may be performed to identify the nature of the obstruction. EUS may be used to obtain biopsy (tissue sample) of suspicious masses.[1] EUS may also replace diagnostic ERCP for stone disease, although this depends on local availability.[3] ## Treatment[edit] ### Fluids and antibiotics[edit] Cholangitis requires admission to hospital. Intravenous fluids are administered, especially if the blood pressure is low, and antibiotics are commenced. Empirical treatment with broad-spectrum antibiotics is usually necessary until it is known for certain which pathogen is causing the infection, and to which antibiotics it is sensitive. Combinations of penicillins and aminoglycosides are widely used, although ciprofloxacin has been shown to be effective in most cases, and may be preferred to aminoglycosides because of fewer side effects. Metronidazole is often added to specifically treat the anaerobic pathogens, especially in those who are very ill or at risk of anaerobic infections. Antibiotics are continued for 7–10 days.[1] Drugs that increase the blood pressure (vasopressors) may also be required to counter the low blood pressure.[2] ### Endoscopy[edit] The definitive treatment for cholangitis is relief of the underlying biliary obstruction.[1] This is usually deferred until 24–48 hours after admission, when the patient is stable and has shown some improvement with antibiotics, but may need to happen as an emergency in case of ongoing deterioration despite adequate treatment,[1] or if antibiotics are not effective in reducing the signs of infection (which happens in 15% of cases).[2][3] Endoscopic retrograde cholangiopancreatography (ERCP) is the most common approach in unblocking the bile duct. This involves endoscopy (passing a fiberoptic tube through the stomach into the duodenum), identification of the ampulla of Vater and insertion of a small tube into the bile duct. A sphincterotomy (making a cut in the sphincter of Oddi) is typically done to ease the flow of bile from the duct and to allow insertion of instruments to extract gallstones that are obstructing the common bile duct; alternatively or additionally, the common bile duct orifice can be dilated with a balloon.[15] Stones may be removed either by direct suction or by using various instruments, including balloons and baskets to trawl the bile duct in order to pull stones into the duodenum. Obstructions that are caused by larger stones may require the use of an instrument known as a mechanical lithotriptor in order to crush the stone prior to removal.[16] Obstructing stones that are too large to be removed or broken mechanically by ERCP may be managed by extracorporeal shock wave lithotripsy. This technique uses acoustic shock waves administered outside the body to break down the stones.[17] An alternative technique to remove very large obstructing stones is electrohydraulic lithotripsy, where a small endoscope known as a cholangioscope is inserted by ERCP to directly visualize the stone. A probe uses electricity to generate shock waves that break down the obstructing stone.[18] Rarely, surgical exploration of the common bile duct (termed choledochotomy), which can be performed with laparoscopy, is required to remove the stone.[19] Narrowed areas may be bridged by a stent, a hollow tube that keeps the duct open. Removable plastic stents are used in uncomplicated gallstone disease, while permanent self-expanding metal stents with a longer lifespan are used if the obstruction is due to pressure from a tumor such as pancreatic cancer. A nasobiliary drain may be left behind; this is a plastic tube that passes from the bile duct through the stomach and the nose and allows continuous drainage of bile into a receptible. It is similar to a nasogastric tube, but passes into the common bile duct directly, and allows for serial x-ray cholangiograms to be done to identify the improvement of the obstruction. The decision on which of the aforementioned treatments to apply is generally based on the severity of the obstruction, findings on other imaging studies, and whether the patient has improved with antibiotic treatment.[1] Certain treatments may be unsafe if blood clotting is impaired, as the risk of bleeding (especially from sphincterotomy) is increased in the use of medication such as clopidogrel (which inhibits platelet aggregation) or if the prothrombin time is significantly prolonged. For a prolonged prothrombin time, vitamin K or fresh frozen plasma may be administered to reduce bleeding risk.[1] ### Percutaneous biliary drainage[edit] In cases where a person is too ill to tolerate endoscopy or when a retrograde endoscopic approach fails to access the obstruction, a percutaneous transhepatic cholangiogram (PTC) may be performed to evaluate the biliary system for placement of a percutaneous biliary drain (PBD).[20][3] This is often necessary in the case of a proximal stricture or a bilioenteric anastomosis (a surgical connection between the bile duct and small bowel, such as the duodenum or jejunum).[2] Once access across the stricture is obtained, balloon dilation can be performed and stones can be swept forward into the duodenum.[20] Due to potential complications of percutaneous biliary drain placement and the necessity of regular drain maintenance,[2] a retrograde approach via ERCP remains first-line therapy.[1] ### Cholecystectomy[edit] Not all gallstones implicated in ascending cholangitis actually originate from the gallbladder, but cholecystectomy (surgical removal of the gallbladder) is generally recommended in people who have been treated for cholangitis due to gallstone disease. This is typically delayed until all symptoms have resolved and ERCP or MRCP have confirmed that the bile duct is clear of gallstones.[1][2][3] Those who do not undergo cholecystectomy have an increased risk of recurrent biliary pain, jaundice, further episodes of cholangitis, and need for further ERCP or cholecystostomy; the risk of death is also significantly increased.[21] ## Prognosis[edit] Acute cholangitis carries a significant risk of death, the leading cause being irreversible shock with multiple organ failure (a possible complication of severe infections).[7] Improvements in diagnosis and treatment have led to a reduction in mortality: before 1980, the mortality rate was greater than 50%, but after 1980 it was 10–30%.[7] Patients with signs of multiple organ failure are likely to die unless they undergo early biliary drainage and treatment with systemic antibiotics. Other causes of death following severe cholangitis include heart failure and pneumonia.[22] Risk factors indicating an increased risk of death include older age, female gender, a history of liver cirrhosis, biliary narrowing due to cancer, acute kidney injury and the presence of liver abscesses.[23] Complications following severe cholangitis include kidney failure, respiratory failure (inability of the respiratory system to oxygenate blood and/or eliminate carbon dioxide), abnormal heart rhythms, wound infection, pneumonia, gastrointestinal bleeding and myocardial ischemia (lack of blood flow to the heart, leading to heart attacks).[22] ## Epidemiology[edit] In the Western world, about 15% of all people have gallstones in their gallbladder but the majority are unaware of this and have no symptoms. Over ten years, 15–26% will suffer one or more episodes of biliary colic (abdominal pain due to the passage of gallstones through the bile duct into the digestive tract), and 2–3% will develop complications of obstruction: acute pancreatitis, cholecystitis or acute cholangitis.[3] Prevalence of gallstone disease increases with age and body mass index (a marker of obesity). However, the risk is also increased in those who lose weight rapidly (e.g. after weight loss surgery) due to alterations in the composition of the bile that makes it prone to form stones. Gallstones are slightly more common in women than in men, and pregnancy increases the risk further.[24] ## History[edit] Dr Jean-Martin Charcot, working at the Salpêtrière Hospital in Paris, France, is credited with early reports of cholangitis, as well as his eponymous triad, in 1877.[4] He referred to the condition as "hepatic fever" (fièvre hépatique).[4][7] Dr Benedict M. Reynolds, an American surgeon, reignited interest in the condition in his 1959 report with colleague Dr Everett L. Dargan, and formulated the pentad that carries his name.[5] It remained a condition generally treated by surgeons, with exploration of the bile duct and excision of gallstones, until the ascendancy of ERCP in 1968.[25] ERCP is generally performed by internal medicine or gastroenterology specialists. In 1992 it was shown that ERCP was generally safer than surgical intervention in ascending cholangitis.[26] ## See also[edit] * Primary sclerosing cholangitis (an autoimmune disease leading to narrowing of the bile ducts) * Gallstone-related pancreatitis ## References[edit] 1. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab Kinney TP (April 2007). "Management of ascending cholangitis". Gastrointest Endosc Clin N Am. 17 (2): 289–306. doi:10.1016/j.giec.2007.03.006. PMID 17556149. 2. ^ a b c d e f g h i j k Oddsdóttir M, Hunter JG (2005). "Gallbladder and the extrahepatic biliary system (chapter 31)". In Brunicardi FC, Anderson DK, Billiar TR, Dunn DL, Hunter JG, Pollock RE (eds.). Schwartz's Principles of Surgery (Eighth ed.). McGraw-Hill. p. 1203. ISBN 978-0-07-141090-8. 3. ^ a b c d e f g Williams EJ, Green J, Beckingham I, Parks R, Martin D, Lombard M (2008). "Guidelines on the management of common bile duct stones". Gut. 57 (7): 1004–1021. doi:10.1136/gut.2007.121657. PMID 18321943. S2CID 206945855. 4. ^ a b c Charcot JM (2004) [1877]. Leçons sur les maladies du foie, des voies biliaires et des reins faites à la Faculté de médecine de Paris: Recueillies et publiées par Bourneville et Sevestre. Paris: Bureaux du Progrés Médical & Adrien Delahaye. ISBN 978-1-4212-1387-3. 5. ^ a b Reynolds BM, Dargan EL (August 1959). "Acute obstructive cholangitis; a distinct clinical syndrome". Ann Surg. 150 (2): 299–303. doi:10.1097/00000658-195908000-00013. PMC 1613362. PMID 13670595. 6. ^ Lim JH (2011). "Liver flukes: the malady neglected". Korean J Radiol. 12 (3): 269–79. doi:10.3348/kjr.2011.12.3.269. PMC 3088844. PMID 21603286. 7. ^ a b c d Kimura Y, Takada T, Kawarada Y, et al. (2007). "Definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis: Tokyo Guidelines". J Hepatobiliary Pancreat Surg. 14 (1): 15–26. doi:10.1007/s00534-006-1152-y. PMC 2784509. PMID 17252293. 8. ^ Brand, M; Bizos, D; O'Farrell P, Jr (6 October 2010). "Antibiotic prophylaxis for patients undergoing elective endoscopic retrograde cholangiopancreatography". The Cochrane Database of Systematic Reviews (10): CD007345. doi:10.1002/14651858.CD007345.pub2. PMID 20927758. 9. ^ Dooley JS (1999). Oxford textbook of clinical hepatology. Oxford University Press. p. 1650. ISBN 978-0-19-262515-1. 10. ^ Huang T, Bass JA, Williams RD (May 1969). "The significance of biliary pressure in cholangitis". Arch Surg. 98 (5): 629–632. doi:10.1001/archsurg.1969.01340110121014. PMID 4888283. 11. ^ Sung JY, Costerton JW, Shaffer EA (May 1992). "Defense system in the biliary tract against bacterial infection". Dig Dis Sci. 37 (5): 689–96. doi:10.1007/BF01296423. PMID 1563308. S2CID 21258760. 12. ^ Sung JJ, Lyon DJ, Suen R, Chung SC, Co AL, Cheng AF, Leung JW, Li AK (June 1995). "Intravenous ciprofloxacin as treatment for patients with acute suppurative cholangitis: a randomized, controlled clinical trial". J Antimicrob Chemother. 35 (6): 855–864. doi:10.1093/jac/35.6.855. PMID 7559196. 13. ^ Chetana Vaishnavi (2013). Infections of the Gastrointestinal System. JP Medical Ltd. p. 511. ISBN 9789350903520. 14. ^ a b Varghese JC, Liddell RP, Farrell MA, Murray FE, Osborne DH, Lee MJ (January 2000). "Diagnostic accuracy of magnetic resonance cholangiopancreatography and ultrasound compared with direct cholangiography in the detection of choledocholithiasis". Clin Radiol. 55 (1): 25–35. doi:10.1053/crad.1999.0319. PMID 10650107. 15. ^ Heo JH, Kang DH, Jung HJ, et al. (October 2007). "Endoscopic sphincterotomy plus large-balloon dilation versus endoscopic sphincterotomy for removal of bile-duct stones". Gastrointest Endosc. 66 (4): 720–6, quiz 768, 771. doi:10.1016/j.gie.2007.02.033. PMID 17905013. 16. ^ Caddy GR, Tham TC (2006). "Gallstone disease: Symptoms, diagnosis and endoscopic management of common bile duct stones". Best Pract Res Clin Gastroenterol. 20 (6): 1085–101. doi:10.1016/j.bpg.2006.03.002. PMID 17127190. 17. ^ Hochberger J, Tex S, Maiss J, Hahn EG (October 2003). "Management of difficult common bile duct stones". Gastrointest Endosc Clin N Am. 13 (4): 623–34. doi:10.1016/S1052-5157(03)00102-8. PMID 14986790. 18. ^ Arya N, Nelles SE, Haber GB, Kim YI, Kortan PK (December 2004). "Electrohydraulic lithotripsy in 111 patients: a safe and effective therapy for difficult bile duct stones". Am J Gastroenterol. 99 (12): 2330–4. PMID 15571578. 19. ^ Karaliotas C, Sgourakis G, Goumas C, Papaioannou N, Lilis C, Leandros E (December 2007). "Laparoscopic common bile duct exploration after failed endoscopic stone extraction". Surg Endosc. 22 (8): 1826–31. doi:10.1007/s00464-007-9708-8. PMID 18071799. S2CID 2347888. 20. ^ a b García-García, Lorenzo; Lanciego, Carlos (2004-03-01). "Percutaneous Treatment of Biliary Stones: Sphincteroplasty and Occlusion Balloon for the Clearance of Bile Duct Calculi". American Journal of Roentgenology. 182 (3): 663–670. doi:10.2214/ajr.182.3.1820663. ISSN 0361-803X. PMID 14975967. 21. ^ McAlister VC, Davenport E, Renouf E (2007). McAlister V (ed.). "Cholecystectomy deferral in patients with endoscopic sphincterotomy". Cochrane Database Syst Rev (4): CD006233. doi:10.1002/14651858.CD006233.pub2. PMID 17943900. Archived from the original on 2012-07-16. 22. ^ a b Lai EC, Tam PC, Paterson IA, Ng MM, Fan ST, Choi TK, Wong J (January 1990). "Emergency surgery for severe acute cholangitis. The high-risk patients". Ann Surg. 211 (1): 55–9. doi:10.1097/00000658-199001000-00009. PMC 1357893. PMID 2294844. 23. ^ Gigot JF, Leese T, Coutinho J, Castaing D, Bismuth H (April 1989). "Acute cholangitis. Multivariate analysis of risk factors". Ann Surg. 209 (4): 435–8. doi:10.1097/00000658-198904000-00008. PMC 1493983. PMID 2930289. 24. ^ Bateson MC (June 1999). "Fortnightly review: gallbladder disease". BMJ. 318 (7200): 1745–8. doi:10.1136/bmj.318.7200.1745. PMC 1116086. PMID 10381713. 25. ^ McCune WS, Shorb PE, Moscovitz H (May 1968). "Endoscopic cannulation of the ampulla of vater: a preliminary report". Ann Surg. 167 (5): 752–6. doi:10.1097/00000658-196805000-00013. PMC 1387128. PMID 5646296. 26. ^ Lai EC, Mok FP, Tan ES, et al. (June 1992). "Endoscopic biliary drainage for severe acute cholangitis". N Engl J Med. 326 (24): 1582–6. doi:10.1056/NEJM199206113262401. hdl:10722/45379. PMID 1584258. ## External links[edit] Classification D * ICD-10: K83.9 * ICD-9-CM: 576.1 * MeSH: D002761 * DiseasesDB: 2514 External resources * MedlinePlus: 000290 * eMedicine: emerg/96 med/2665 * Patient UK: Ascending cholangitis Wikimedia Commons has media related to Ascending cholangitis. 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3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Ascending cholangitis	c0008311	28,597	wikipedia	https://en.wikipedia.org/wiki/Ascending_cholangitis	2021-01-18T19:02:47	{"mesh": ["D002761"], "umls": ["C0008311"], "wikidata": ["Q603644"]}
Periodic limb movement disorder SpecialtyNeurology Periodic limb movement disorder (PLMD) is a sleep disorder where the patient moves limbs involuntarily and periodically during sleep, and has symptoms or problems related to the movement. PLMD should not be confused with restless legs syndrome (RLS). RLS is characterized by a voluntary response to an urge to move legs due to discomfort. PLMD on the other hand is involuntary, and the patient is often unaware of these movements altogether. Periodic limb movements (PLMS) occurring during daytime period can be found but are considered as a symptom of RLS. Only PLMS during sleep can suggest a diagnosis of PLMD.[1] Periodic limb movement disorder is characterized by recurrent episodes of frequent limb movements while sleeping. It mostly happens in the lower parts of the body like the toes, ankles, knees and hips. It can also, in some cases, appear in the upper extremities of the body. These movements can lead the patient to wake up, and if so, sleep interruption can be the origin of excessive daytime sleepiness.[2] PLMD is characterized by increased periodic limb movements during sleep (PLMS), which must coexist with a sleep disturbance or other functional impairment, in an explicit cause-effect relationship.[3][4] Usually, these involuntary movements come from lower extremities (including toes, ankles, knees, and hips), although they can also be observed in upper extremities, occasionally.[5] PLMS seem to be common features within many people, and identifying whether or not these movements are clinically relevant for a distinct diagnosis of PLMD remains a challenge for clinical and scientific fields.[4][5] Moreover, diagnosis of PLMD cannot be used when narcolepsy, restless legs syndrome (RLS), REM sleep behaviour disorder (RBD) or untreated obstructive sleep apnea (OSA) is already diagnosed, since abnormal movements during sleep are frequent in these disorders.[3][4] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 3.1 Classification * 4 Treatment * 5 Epidemiology * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] People with PLMD often have excessive daytime sleepiness (EDS), falling asleep during the day, trouble falling asleep at night, and difficulty staying asleep throughout the night. Patients also display involuntary limb movements that occur at periodic intervals anywhere from 20–40 seconds apart. They often only last the first half of the night during non-REM sleep stages. Movements do not occur during REM because of muscle atonia. PLMS can be unilateral or bilateral and not really symmetrical or simultaneous.[6] PLMS is often a symptom of RLS but evidence for differences between those two sleep disorders was found in literature. Sleep structure differed, when RLS patients had significantly more REM sleep and less stage 1 sleep compared to PLMD patients. Besides, PLMI was significantly higher in patients with PLMD.[7] ## Causes[edit] It is mostly unknown what causes PLMD, but in many cases the patient also has other medical problems such as Parkinson's disease or narcolepsy. Medical agents must be taken into consideration: several psychopharmacological drugs (serotonergic and tricyclic antidepressants, venlafaxine and mirtazapine) and therefore heighten the risk of PLMD.[4] For women, the presence of musculoskeletal disease, heart disease, obstructive sleep apnea, cataplexy, doing physical activities close to bedtime and the presence of a mental disorder were significantly associated with having a higher risk of both PLMD and restless legs syndrome.[8] PLMS seem to find an origin in the spinal cord.[1] In fact, PLMS was suggested to be associated with increased spinal reflexes. Manifestations of PLMS seems to occur mostly in disorders associated with dopaminergic dysfunctions.[9] Hypothesis of low ferritin levels in adult population was raised to explain PLMD where increased RLS severity and increased PLMS were significantly correlated with low ferritin levels. Research evidence suggested iron is possibly contributing to PLMD. Thus, lack of iron may induce inhibition of dopamine formation which might underlie PLMS.[10] ## Diagnosis[edit] 5 minute segment of a polysomnogram, demonstrating 7 PLMs with arousals People with PLMD often do not know the cause of their excessive daytime sleepiness and their limb movements are reported by a spouse or sleep partner. PLMD cannot be diagnosed by polysomnogram (PSG) alone, it is necessary to obtain a full medical history and taking into account all available information.[4] Polysomnography is recognized as the assessment method which brings most precise information on sleep quality, sleep structure and physiological parameters during sleep (respiration, heart rate, movements). Therefore, diagnostic of PLMD can usually be established only in laboratory settings. As people usually ignore the cause of their daytime impairments, PLMS during sleep are mostly found through laboratory examination rather than clinical complaints.[1] Video-Polysomnography may be recommended to distinguish PLMS from other leg movements during sleep time which may be similar to PLMS when it comes to duration and pattern. Measures from PSG allocated to the diagnostic of PLMD are essentially based on electromyography (EMG) measuring muscle activity. EMG electrodes are usually placed on anterior tibialis muscle.[1] Recent studies showed actigraphy may be combined to PSG as a screening tool for PLMD diagnosis. Actigraphs are watch-shaped device - usually worn by adult population on the wrist - used to record sleep and wake periods for at least a week. Recent actigraphy devices allow more precise recordings which helps evaluating if actual movements meet diagnostic criteria for PLMD. Recent studies showed actigraph records reflect quite accurately PLMI criterion.[1] Crucial for the diagnosis are the inter-movement intervals and the frequency of PLMS - each movement must happen within a 4 to 90 second interval from the previous movement. The periodic limb movement index (PLMI), which corresponds to the number of periodic limb movements per hour, must be more than 15 movements per hour in adults and 5 movements or more per hour in children.[4] The diagnosis of PLMD requires a visible cause-effect relationship between PLMS and an observed sleep disturbance or daytime impairment (both disturbance and impairment have to be clinically significant).[4] Other relevant causes of Insomnia and Hypersomnia have to be ruled out before diagnosing PLMD (most importantly anxiety, obstructive sleep apnea, and narcolepsy).[4] Furthermore, symptoms can not be better explained by any other conditions.[4] For the differential diagnosis it is important to differentiate PLMD from other leg movements during sleep, which are high-frequency:[4] * alternating leg movement activity (ALMA) are very similar events and could be mistaken for PLMS * hypnagogic foot tremor (HFT) events are also very similar to PLMS and could be misdiagnosed * excessive fragmentary myoclonus (EFM) events are shorter than PLMS ### Classification[edit] PLMD is classified in the third edition of the International Classification of Sleep Disorders (ICSD-3) which presents current sleep disorders nosology. ICSD-3 is divided in 7 sections and PLMD is classified in the Sleep-Related Movement Disorders' section.[11] There are some updates from ICSD-2.[12] The diagnosis is more strict.[12] A simple complaint is no longer enough: a significant clinical impairment is needed.[12] Sleep impairments need to be clearly caused by PLMS and the symptoms also need to be explained solely by the PLMS.[12] ## Treatment[edit] PLMD can be effectively treated with dopaminergic agents (pramipexole, ropinirole, cabergoline, and rotigotine) and it has been found that patients with a low ferritin level respond well to oral iron supplements.[4] Adverse effects of these agents have been reported and include the occurrence of restless leg syndrome triggered by the medication, as well as cortical arousals, which are a cause of disturbed sleep.[4] Patients must stay on these medications in order to experience relief, because there is no known cure for this disorder. PLMs tend to be exacerbated by tricyclic antidepressants, SSRIs, stress, and sleep deprivation. It is also advised not to consume caffeine, alcohol, or antidepressants as these substances could worsen the PLMD symptoms. Other medications aimed at reducing or eliminating the leg jerks or the arousals can be prescribed. Non-ergot derived dopaminergic medications (pramipexole and ropinirole) are preferred.[13] Other dopaminergic agents such as co-careldopa, co-beneldopa, pergolide, or lisuride may also be used. These medications decrease or eliminate both the leg jerks and the arousals. These medications are also successful for the treatment of restless legs syndrome. In one study, co-careldopa was superior to dextropropoxyphene in decreasing the number of leg kicks and the number of arousals per hour of sleep. However, co-careldopa and, to a lesser extent, pergolide may shift the leg movements from the nighttime to the daytime.[14] Clonazepam in doses of 1 mg has been shown to improve objective and subjective measures of sleep.[15] Hypothesis was presented for supplementation of magnesium use for PLMD improvement due to evidence for therapeutic effects of magnesium on normal magnesium level patients with insomnia and RLS.[16][6] Evidence of magnesium on pathomechanisms of PLMD has yet to be found. However, it remains insufficient evidences related to the efficacy of pharmacological treatment in PLMD, and its use has been based on the dopaminergic medication effect on RLS.[5] Therefore, a careful clinical monitoring with any pharmacological use in PLMD is recommended.[5] ## Epidemiology[edit] PLMD is estimated to occur in approximately 4% of adults (aged 15–100),[8] but is more common in the elderly, especially females, with up to 11% experiencing symptoms.[17] PLMD appears to be related to restless legs syndrome (RLS) - a study of 133 people found that 80% of those with RLS also had PLMS.[18] However the opposite is not true: many people who have PLMS do not also have restless legs syndrome.[18][19] PLMD is an uncommon childhood disorder. Based on adult criteria and PSG analysis, studies showed prevalence of isolated PLMD in children population with no other comorbidity about 1.2 to 1.5%. There was also evidence for 5.6 to 7.7% of children with PLMI > 5/hr.[20][21] Periodic limb movements during sleep are associated with a lower quality of life in children with monosymptomatic nocturnal enuresis[22] ## See also[edit] * Hypnic jerk * Restless legs syndrome ## References[edit] 1. ^ a b c d e Hening W (September 2004). "The clinical neurophysiology of the restless legs syndrome and periodic limb movements. Part I: diagnosis, assessment, and characterization". Clinical Neurophysiology. 115 (9): 1965–74. doi:10.1016/j.clinph.2004.03.032. PMID 15294199. 2. ^ Aurora RN, Kristo DA, Bista SR, Rowley JA, Zak RS, Casey KR, et al. (August 2012). "The treatment of restless legs syndrome and periodic limb movement disorder in adults--an update for 2012: practice parameters with an evidence-based systematic review and meta-analyses: an American Academy of Sleep Medicine Clinical Practice Guideline". Sleep. 35 (8): 1039–62. doi:10.5665/sleep.1988. PMC 3397811. PMID 22851801. 3. ^ a b Sateia MJ (November 2014). "International classification of sleep disorders-third edition: highlights and modifications". Chest. Elsevier BV. 146 (5): 1387–1394. doi:10.1378/chest.14-0970. PMID 25367475. 4. ^ a b c d e f g h i j k l Fulda, Stephany (2018-03-01). "Periodic Limb Movement Disorder: a Clinical Update". Current Sleep Medicine Reports. 4 (1): 39–49. doi:10.1007/s40675-018-0107-6. ISSN 2198-6401. 5. ^ a b c d Aurora RN, Kristo DA, Bista SR, Rowley JA, Zak RS, Casey KR, et al. (August 2012). "Update to the AASM Clinical Practice Guideline: "The treatment of restless legs syndrome and periodic limb movement disorder in adults-an update for 2012: practice parameters with an evidence-based systematic review and meta-analyses"". Sleep. Oxford University Press (OUP). 35 (8): 1037. doi:10.5665/sleep.1986. PMC 3397810. PMID 22851800. 6. ^ a b Rijsman RM, de Weerd AW (June 1999). "Secondary periodic limb movement disorder and restless legs syndrome". Sleep Medicine Reviews. 3 (2): 147–58. doi:10.1016/S1087-0792(99)90021-7. PMID 15310483. 7. ^ Eisensehr I, Ehrenberg BL, Noachtar S (March 2003). "Different sleep characteristics in restless legs syndrome and periodic limb movement disorder". Sleep Medicine. 4 (2): 147–52. doi:10.1016/S1389-9457(03)00004-2. PMID 14592346. 8. ^ a b Ohayon MM, Roth T (July 2002). "Prevalence of restless legs syndrome and periodic limb movement disorder in the general population". Journal of Psychosomatic Research. Elsevier BV. 53 (1): 547–54. doi:10.1016/s0022-3999(02)00443-9. PMID 12127170. 9. ^ Montplaisir J, Michaud M, Denesle R, Gosselin A (April 2000). "Periodic leg movements are not more prevalent in insomnia or hypersomnia but are specifically associated with sleep disorders involving a dopaminergic impairment". Sleep Medicine. 1 (2): 163–167. doi:10.1016/S1389-9457(00)00014-9. PMID 10767664. 10. ^ Sun ER, Chen CA, Ho G, Earley CJ, Allen RP (June 1998). "Iron and the restless legs syndrome". Sleep. 21 (4): 371–7. doi:10.1093/sleep/21.4.381. PMID 9646381. 11. ^ Sateia MJ (November 2014). "International classification of sleep disorders-third edition: highlights and modifications". Chest. 146 (5): 1387–1394. doi:10.1378/chest.14-0970. PMID 25367475. 12. ^ a b c d Fulda, S. (2018). Periodic Limb Movement Disorder: A Clinical Update. Current Sleep Medicine Reports, 4(1), 39‑49. https://doi.org/10.1007/s40675-018-0107-6 13. ^ "Periodic Limb Movements in Sleep". Armenian Health Network, Health.am. Sep 21, 2006. Retrieved 2009-07-15. 14. ^ Kaplan PW, Allen RP, Buchholz DW, Walters JK (December 1993). "A double-blind, placebo-controlled study of the treatment of periodic limb movements in sleep using carbidopa/levodopa and propoxyphene". Sleep. Oxford University Press (OUP). 16 (8): 717–23. doi:10.1093/sleep/16.8.717. PMID 8165385. 15. ^ Saletu M, Anderer P, Saletu-Zyhlarz G, Prause W, Semler B, Zoghlami A, et al. (April 2001). "Restless legs syndrome (RLS) and periodic limb movement disorder (PLMD): acute placebo-controlled sleep laboratory studies with clonazepam". European Neuropsychopharmacology. Elsevier BV. 11 (2): 153–61. doi:10.1016/s0924-977x(01)00080-3. PMID 11313161. 16. ^ Hornyak M, Voderholzer U, Hohagen F, Berger M, Riemann D (August 1998). "Magnesium therapy for periodic leg movements-related insomnia and restless legs syndrome: an open pilot study". Sleep. 21 (5): 501–5. doi:10.1093/sleep/21.5.501. PMID 9703590. 17. ^ Hornyak M, Trenkwalder C (May 2004). "Restless legs syndrome and periodic limb movement disorder in the elderly". Journal of Psychosomatic Research. Elsevier BV. 56 (5): 543–8. doi:10.1016/s0022-3999(04)00020-0. PMID 15172211. 18. ^ a b Montplaisir J, Boucher S, Poirier G, Lavigne G, Lapierre O, Lespérance P (January 1997). "Clinical, polysomnographic, and genetic characteristics of restless legs syndrome: a study of 133 patients diagnosed with new standard criteria". Movement Disorders. Wiley. 12 (1): 61–5. doi:10.1002/mds.870120111. PMID 8990055. 19. ^ Ferri R., Novelli L., and Bruni O. (2013) Periodic Limb Movement Disorder. In: Kushida C. (ed.)The Encyclopedia of Sleep, vol. 4, pp. 43-47. Waltham, MA: Academic Press. . 20. ^ Kirk VG, Bohn S (March 2004). "Periodic limb movements in children: prevalence in a referred population". Sleep. 27 (2): 313–5. doi:10.1093/sleep/27.2.313. PMID 15124728. 21. ^ Marcus CL, Traylor J, Gallagher PR, Brooks LJ, Huang J, Koren D, et al. (August 2014). "Prevalence of periodic limb movements during sleep in normal children". Sleep. Oxford University Press (OUP). 37 (8): 1349–52. doi:10.5665/sleep.3928. PMC 4096204. PMID 25083015. 22. ^ Van Herzeele, Charlotte; Dhondt, Karlien; Roels, Sanne Patrick; Raes, Ann; Groen, Luitzen-Albert; Hoebeke, Piet; Vande Walle, Johan (July 2015). "Periodic limb movements during sleep are associated with a lower quality of life in children with monosymptomatic nocturnal enuresis". European Journal of Pediatrics. 174 (7): 897–902. doi:10.1007/s00431-014-2474-4. ## External links[edit] Classification D * ICD-10: G47.8 * ICD-9-CM: 327.51 * MeSH: D009207 * DiseasesDB: 36388 * v * t * e Sleep and sleep disorders Stages of sleep cycles * Rapid eye movement (REM) * Non-rapid eye movement * Slow-wave Brain waves * Alpha wave * Beta wave * Delta wave * Gamma wave * K-complex * Mu rhythm * PGO waves * Sensorimotor rhythm * Sleep spindle * Theta wave Sleep disorders Dyssomnia * Excessive daytime sleepiness * Hypersomnia * Insomnia * Kleine–Levin syndrome * Narcolepsy * Night eating syndrome * Nocturia * Sleep apnea * Catathrenia * Central hypoventilation syndrome * Obesity hypoventilation syndrome * Obstructive sleep apnea * Periodic breathing * Sleep state misperception Circadian rhythm disorders * Advanced sleep phase disorder * Cyclic alternating pattern * Delayed sleep phase disorder * Irregular sleep–wake rhythm * Jet lag * Non-24-hour sleep–wake disorder * Shift work sleep disorder Parasomnia * Bruxism * Nightmare disorder * Night terror * Periodic limb movement disorder * Rapid eye movement sleep behavior disorder * Sleepwalking * Somniloquy Benign phenomena * Dreams * Exploding head syndrome * Hypnic jerk * Hypnagogia / Sleep onset * Hypnopompic state * Sleep paralysis * Sleep inertia * Somnolence * Nocturnal clitoral tumescence * Nocturnal penile tumescence * Nocturnal emission Treatment * Sleep diary * Sleep hygiene * Sleep induction * Hypnosis * Lullaby * Somnology * Polysomnography Other * Sleep medicine * Behavioral sleep medicine * Sleep study Daily life * Bed * Bunk bed * Daybed * Four-poster bed * Futon * Hammock * Mattress * Sleeping bag * Bed bug * Bedding * Bedroom * Bedtime * Bedtime story * Bedtime toy * Biphasic and polyphasic sleep * Chronotype * Dream diary * Microsleep * Mouth breathing * Nap * Nightwear * Power nap * Second wind * Siesta * Sleep and creativity * Sleep and learning * Sleep deprivation / Sleep debt * Sleeping while on duty * Sleepover * Snoring [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	Periodic limb movement disorder	c0751774	28,598	wikipedia	https://en.wikipedia.org/wiki/Periodic_limb_movement_disorder	2021-01-18T18:57:35	{"mesh": ["D020189"], "umls": ["C0751774", "C1561887"], "wikidata": ["Q13038909"]}
A number sign (#) is used with this entry because of evidence that mild encephalitis/encephalopathy with reversible myelin vacuolization (MMERV) is caused by heterozygous mutation in the MYRF gene (608329) on chromosome 11q12. Description MMERV is an episodic acute reversible encephalopathy that occurs in children and is frequently associated with a trigger, such as a febrile illness. Affected individuals have impaired consciousness, delirious behavior, and/or seizures with lip smacking or eye deviation. These changes are associated with white matter lesions in the brain that often occur in the splenium of the corpus callosum, but may occur in surrounding areas. The acute phase of the disorder can be treated with steroids, and most patients make a full neurologic recovery between episodes with no sequelae (summary by Kurahashi et al., 2018). Clinical Features Kurahashi et al. (2018) reported 2 unrelated Japanese families with onset of episodic encephalopathy in childhood. There were 4 definitely affected individuals from the 2 families. Five additional members from 1 family had a history suggestive of the disorder, although brain imaging was not performed. The proband in family A developed seizures at age 32 months, followed by repeated episodes of altered consciousness in the following few years, but had no neurologic sequelae at 106 months of age. Brain imaging showed signal abnormalities in the corpus callosum and white matter consistent with myelin changes. Family history revealed several additional family members with a history of single similar events in childhood, including speech difficulties, seizures, and abnormal behavior. None had permanent neurologic sequelae. In family B, 3 sisters had a similar disorder between 2 and 9 years of age. Their mother was also affected at age 6. Brain imaging in the sisters showed white matter vacuolization abnormalities in the corpus callosum and surrounding areas, all of which resolved in days to a week. Family B had previously been reported by Imamura et al. (2010). Inheritance The transmission pattern of MMERV in the families reported by Kurahashi et al. (2018) was consistent with autosomal dominant inheritance. Molecular Genetics In 9 patients from 2 unrelated Japanese families with MMERV, Kurahashi et al. (2018) identified a heterozygous missense mutation in the MYRF gene (Q403R; 608329.0001). The mutation, which was found by whole-exome sequencing in the first family and confirmed by Sanger sequencing in both families, segregated with the disorder in both families. Haplotype analysis suggested a founder effect. In vitro functional expression studies using a luciferase reporter showed that the mutation resulted in significantly decreased transcriptional activity. Since all patients had normal psychomotor development even after recurrent episodes, Kurahashi et al. (2018) suggested that the function of the MYRF variant is relatively preserved under normal circumstances, but is insufficient during increased physiologic demands, such as infection. Direct sequencing of the MYRF gene in 33 individuals with sporadic MMERV did not identify any pathogenic variants. Animal Model Koenning et al. (2012) found that genetic ablation of the Mrf (Myrf) gene in mature oligodendrocytes in adult mice resulted in a delayed and severe demyelination. The mice had impaired motor skill learning. The demyelination was accompanied by microglial/macrophage infiltration, axonal damage, and decreased expression of myelin genes. However, over time, there was some evidence of remyelination. The findings demonstrated that ongoing expression of Mrf within the adult central nervous system is critical to maintain mature oligodendrocyte identity and the integrity of myelin. INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Encephalopathy, acute, episodic \- Impaired consciousness, episodic \- Seizures \- Speech difficulties, episodic \- White matter abnormalities in the corpus callosum and surrounding areas \- Myelin vacuolization MISCELLANEOUS \- Onset in childhood \- Episodes may be triggered by fever, infection, stress \- Affected individuals have complete neurologic recovery within days to weeks \- Brain imaging abnormalities are transient and return to normal \- No permanent neurologic sequelae \- Two unrelated Japanese families have been reported (last curated September 2018) MOLECULAR BASIS \- Caused by mutation in the myelin regulatory factor gene (MYRF, 608329.0001 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitor [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens [Diff]: Difference [7d avg]: Average of the last 7 days [per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population [Cases per 100k]: Cases per 100,000 county population [Deaths per 100k]: Deaths per 100,000 county population [Percent]: Percent of total in category [Rate]: ICU-care cases per confirmed cases in each category [GER]: Germany [FRA]: France [ITA]: Italy [ESP]: Spain [DEN]: Denmark [SUI]: Switzerland [USA]: United States [COL]: Colombia [KAZ]: Kazakhstan [NED]: Netherlands [LIT]: Lithuania [POR]: Portugal [AUT]: Austria [AUS]: Australia [RUS]: Russia [LUX]: Luxembourg [UKR]: Ukraine [SLO]: Slovenia [GBR]: Great Britain [CZE]: Czech Republic [BEL]: Belgium [CAN]: Canada [DHT]: Dihydrotestosterone [IM]: intramuscular injection [SC]: subcutaneous injection [MRIs]: monoamine reuptake inhibitors [GHB]: γ-hydroxybutyric acid [pop.]: population [et al.]: et alia (and others) [a.k.a.]: also known as [mRNA]: messenger RNA [kDa]: kilodalton [EPC]: Early Prostate Cancer [LAPC]: locally advanced prostate cancer [NSAAs]: nonsteroidal antiandrogens [NSAA]: nonsteroidal antiandrogen [GnRH]: gonadotropin-releasing hormone [ADT]: androgen deprivation therapy [LH]: Luteinizing hormone [AR]: Androgen receptor [CAB]: combined androgen blockade [LPC]: localized prostate cancer [CPA]: cyproterone acetate [U.S.]: United States [FDA]: Food and Drug Administration [lit.]: literal translation [CMPF]: 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid [No.]: Number [XLSMA]: X-linked spinal muscular atrophies [DSMA]: Distal spinal muscular atrophies [EUA]: emergency use authorization [AAS]: anabolic–androgenic steroid [hCG]: human chorionic gonadotropin [SARMs]: Selective androgen receptor modulator [GPRC6A]: G protein-coupled receptor family C group 6 member A [SHBG]: Sex hormone-binding globulin [ATP]: Adenosine triphosphate [CNTs]: Concentrative nucleoside transporters [ENTs]: Equilibrative nucleoside transporters [PMAT]: Plasma membrane monoamine transporter [XO]: Xanthine oxidase [[]]: Article is not yet available in this wiki. [Pub.L.]: Public Law (United States) [CFUs]: Colony-forming units [nm]: nanometer [CRF]: corticotropin-releasing factor [cAMP]: cyclic adenosine monophosphate [†]: Extinct [VDCCs]: voltage-dependent calcium channels [ADHD]: Attention-deficit hyperactivity disorder [CNS]: central nervous system [PPD]: Paranoid Personality Disorder [SzPD]: Schizoid Personality Disorder [StPD]: Schizotypal Personality Disorder [ASPD]: Antisocial Personality Disorder [BPD]: Borderline Personality Disorder [HPD]: Histrionic Personality Disorder [NPD]: Narcissistic Personality Disorder [AvPD]: Avoidant Personality Disorder [DPD]: Dependent Personality Disorder [OCPD]: Obsessive-Compulsive Personality Disorder [PAPD]: Passive-Aggressive Personality Disorder [DpPD]: Depressive Personality Disorder [SDPD]: Self-Defeating Personality Disorder [SaPD]: Sadistic Personality Disorder [m.]: married [MSM]: Men who have sex with men [NI]: Northern Ireland [%DV]: Percentage of Daily Value [NSW DCR]: New South Wales District Court Reports [transl.]: translation [α2δ]: alpha2delta subunit [VDCC]: voltage-gated calcium channel [GABAAR]: GABAA receptor [PAMs]: positive allosteric modulators [H1R]: H1 receptor [TeCAs]: Tetracyclic antidepressants [OXR]: Orexin receptor [MTR]: Melatonin receptor [THC]: tetrahydrocannabinol [5-HTP]: 5-hydroxytryptophan [NRIs]: Norepinephrine reuptake inhibitors [NDRIs]: Norepinephrine–dopamine reuptake inhibitors [NaSSAs]: Noradrenergic and specific serotonergic antidepressants [SARIs]: Serotonin antagonist and reuptake inhibitors [SMS]: Serotonin modulator and stimulators [MAOA]: Monoamine oxidase A [MAOB]: Monoamine oxidase B [SAMe]: S-adenosyl-L-methionine [FSH]: Follicle-stimulating hormone	ENCEPHALITIS/ENCEPHALOPATHY, MILD, WITH REVERSIBLE MYELIN VACUOLIZATION	None	28,599	omim	https://www.omim.org/entry/618113	2019-09-22T15:43:35	{"omim": ["618113"], "synonyms": ["Alternative titles", "ENCEPHALITIS/ENCEPHALOPATHY, MILD, WITH REVERSIBLE SPLENIAL LESION"]}

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